<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01692301</url>
  </required_header>
  <id_info>
    <org_study_id>CLCZ696A2216</org_study_id>
    <secondary_id>2012-002899-14</secondary_id>
    <nct_id>NCT01692301</nct_id>
  </id_info>
  <brief_title>Study of the Safety and Efficacy of LCZ696 on Arterial Stiffness in Elderly Patients With Hypertension</brief_title>
  <official_title>A Randomized, Double-blind 52-week Study to Evaluate the Safety and Efficacy of an LCZ696 Regimen Compared to an Olmesartan Regimen on Arterial Stiffness Through Assessment of Central Blood Pressure in Elderly Patients With Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study examined the efficacy of LCZ696 in comparison to the ARB olmesartan on Central&#xD;
      Aortic Systolic Blood Pressure (CASP) and other measures of central hemodynamics and arterial&#xD;
      stiffness in elderly patients with an elevated systolic blood pressure (SBP) and widened&#xD;
      pulse pressure (PP).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks</measure>
    <time_frame>baseline, 12 weeks</time_frame>
    <description>Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.&#xD;
At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Central Pulse (CPP) Pressure</measure>
    <time_frame>Baseline, 12 weeks, and 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Pulse Wave Velocity (PWV)</measure>
    <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
    <description>Pulse wave velocity recordings were performed on patient while in a supine, face-up position.&#xD;
Tonometry was performed on the carotid simultaneously with the cuff inflation over the femoral artery. Two pulse wave velocity measures, meeting all quality control criteria were captured at baseline, week 12 and week 52.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks</measure>
    <time_frame>baseline, 52 weeks</time_frame>
    <description>Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.&#xD;
At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)</measure>
    <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
    <description>At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)</measure>
    <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
    <description>At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, DBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Sitting Pulse Pressure (msPP)</measure>
    <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
    <description>Mean sitting pulse pressure for each patient and visit was calculated as the difference between the calculated values of mean sitting systolic blood pressure and mean sitting diastolic blood pressure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Arterial Pressure (MAP)</measure>
    <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
    <description>Mean arterial pressure (MAP) was calculated from mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) as (2 * msDBP + msSBP)/3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP)</measure>
    <time_frame>Baseline, 12 weeks, and 52 weeks</time_frame>
    <description>An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maSBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP)</measure>
    <time_frame>Baseline, 12 weeks, and 52 weeks</time_frame>
    <description>An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maDBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP)</measure>
    <time_frame>Baseline, 12 weeks, and 52 weeks</time_frame>
    <description>Mean 24 hour ambulatory pulse pressure was calculated as the difference between the mean 24 hour systolic and diastolic ambulatory blood pressure in corresponding visits i.e. baseline, week 12 and week 52.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">454</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>LCZ696 (sacubitril/valsartan)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Olmesartan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LCZ696</intervention_name>
    <description>200 mg tablet</description>
    <arm_group_label>LCZ696 (sacubitril/valsartan)</arm_group_label>
    <other_name>sacubitril/valsartan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olmesartan</intervention_name>
    <description>20 mg and 40 mg capsules</description>
    <arm_group_label>Olmesartan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LCZ696 matching placebo</intervention_name>
    <description>LCZ696 Matching Placebo tablet</description>
    <arm_group_label>LCZ696 (sacubitril/valsartan)</arm_group_label>
    <arm_group_label>Olmesartan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olmesartan matching placebo</intervention_name>
    <description>Olmesartan matching placebo capsule</description>
    <arm_group_label>LCZ696 (sacubitril/valsartan)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>amlodipine</intervention_name>
    <description>amlodipine 2.5 mg or 5 mg tablets</description>
    <arm_group_label>LCZ696 (sacubitril/valsartan)</arm_group_label>
    <arm_group_label>Olmesartan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>hydrochlorothiazide</intervention_name>
    <description>hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets</description>
    <arm_group_label>LCZ696 (sacubitril/valsartan)</arm_group_label>
    <arm_group_label>Olmesartan</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients ≥ 60 years of age.&#xD;
&#xD;
          2. Patients with essential hypertension, untreated or currently taking antihypertensive&#xD;
             therapy.&#xD;
&#xD;
          3. Untreated patients must have an office msSBP ≥150 mmHg and &lt;180 mmHg at Visit 101 and&#xD;
             Visit 201 if they are newly diagnosed or have not been treated with antihypertensive&#xD;
             drugs for the 4 weeks prior to Visit 1.&#xD;
&#xD;
          4. Treated patients must have an office msSBP ≥140 mmHg and &lt;180 mmHg at Visit 102 (or&#xD;
             Visit 103) and msSBP ≥150 mmHg and &lt;180 mmHg at Visit 201 if they have been treated&#xD;
             with antihypertensive drugs for the 4 weeks prior to Visit 1.&#xD;
&#xD;
          5. All patients must have pulse pressure &gt;60 mmHg at Visit 201. Pulse pressure is defined&#xD;
             as msSBP- msDBP.&#xD;
&#xD;
          6. Patients must have a difference in msSBP within +/-15 mmHg between Visit 201&#xD;
             (randomization) and the visit immediately prior to Visit 201.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg&#xD;
             and/or msSBP ≥ 180 mmHg)&#xD;
&#xD;
          2. History of angioedema, drug-related or otherwise.&#xD;
&#xD;
          3. History or evidence of a secondary form of hypertension, including but not limited to&#xD;
             any of the following: renal parenchymal hypertension, renovascular hypertension&#xD;
             (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary&#xD;
             hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease,&#xD;
             and drug-induced hypertension.&#xD;
&#xD;
          4. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any&#xD;
             history of stroke.&#xD;
&#xD;
          5. History of myocardial infarction, coronary bypass surgery or any percutaneous coronary&#xD;
             intervention (PCI) during the 12 months prior to Visit 1.&#xD;
&#xD;
          6. History of atrial fibrillation or atrial flutter during the 3 months prior to Visit 1,&#xD;
             or active atrial fibrillation or atrial flutter on the ECG at screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Belzoni</city>
        <state>Mississippi</state>
        <zip>39038</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lake Jackson</city>
        <state>Texas</state>
        <zip>77566</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pasadena</city>
        <state>Texas</state>
        <zip>77504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1440AAD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ramos Mejia</city>
        <state>Buenos Aires</state>
        <zip>B1704ETD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>S2000CXH</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barranquilla</city>
        <state>Atlantico</state>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barranquilla</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nuernberg</city>
        <zip>90471</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Athens</city>
        <zip>11525</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Athens</city>
        <zip>11526</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>54642</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Treviglio</city>
        <state>BG</state>
        <zip>24047</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pisa</city>
        <state>PI</state>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Daniele Del Friuli</city>
        <state>UD</state>
        <zip>33038</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shimotsuke-city</city>
        <state>Tochigi</state>
        <zip>329-0498</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucheon</city>
        <state>Gyeonggi-do</state>
        <zip>424-717</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>110 744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>101990</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>117198</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>119992</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Saint Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>197341</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150047</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sevilla</city>
        <state>Andalucia</state>
        <zip>41071</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jerez de La Frontera</city>
        <state>Cadiz</state>
        <zip>11407</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Cataluna</state>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Terrassa</city>
        <state>Catalunya</state>
        <zip>08221</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Centelles</city>
        <state>Cataluña</state>
        <zip>08540</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Puerto de Sagunto</city>
        <state>Comunidad Valenciana</state>
        <zip>46520</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>La Coruna</city>
        <state>Galicia</state>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <state>Taiwan, ROC</state>
        <zip>112</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>114</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Colombia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Brazil</country>
  </removed_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>September 20, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <results_first_submitted>March 31, 2016</results_first_submitted>
  <results_first_submitted_qc>March 31, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 4, 2016</results_first_posted>
  <last_update_submitted>March 31, 2016</last_update_submitted>
  <last_update_submitted_qc>March 31, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 4, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hypertension, elderly, central aortic pulse pressure, central pulse pressure, pulse wave velocity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amlodipine</mesh_term>
    <mesh_term>Valsartan</mesh_term>
    <mesh_term>Hydrochlorothiazide</mesh_term>
    <mesh_term>Olmesartan</mesh_term>
    <mesh_term>Olmesartan Medoxomil</mesh_term>
    <mesh_term>Sacubitril and valsartan sodium hydrate drug combination</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>LCZ696 (Sacubitril/Valsartan)</title>
          <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
        </group>
        <group group_id="P2">
          <title>Olmesartan</title>
          <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="229">&quot;Started&quot; indicates patients in randomized, full analysis and safety set</participants>
                <participants group_id="P2" count="225"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="184"/>
                <participants group_id="P2" count="183"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="42"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance with study treatment</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient/guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Technical problems</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full analysis set - All patients who were randomized.</population>
      <group_list>
        <group group_id="B1">
          <title>LCZ696 (Sacubitril/Valsartan)</title>
          <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
        </group>
        <group group_id="B2">
          <title>Olmesartan</title>
          <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="229"/>
            <count group_id="B2" value="225"/>
            <count group_id="B3" value="454"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68.2" spread="5.73"/>
                    <measurement group_id="B2" value="67.2" spread="5.97"/>
                    <measurement group_id="B3" value="67.7" spread="5.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="110"/>
                    <measurement group_id="B2" value="107"/>
                    <measurement group_id="B3" value="217"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="119"/>
                    <measurement group_id="B2" value="118"/>
                    <measurement group_id="B3" value="237"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks</title>
        <description>Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.&#xD;
At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.</description>
        <time_frame>baseline, 12 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 12).</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks</title>
          <description>Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.&#xD;
At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 12).</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="207"/>
                <count group_id="O2" value="206"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.57" spread="1.01"/>
                    <measurement group_id="O2" value="-8.90" spread="1.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.010</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-3.66</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.42</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.45</ci_lower_limit>
            <ci_upper_limit>-0.87</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Central Pulse (CPP) Pressure</title>
        <time_frame>Baseline, 12 weeks, and 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 12, week 52). Four patients did not have a successful CASP assessment at Week 12 but passed quality check at Week 52, thus 4 more patients were included in the Week 52 Endpoint analysis</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Central Pulse (CPP) Pressure</title>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 12, week 52). Four patients did not have a successful CASP assessment at Week 12 but passed quality check at Week 52, thus 4 more patients were included in the Week 52 Endpoint analysis</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 12 (n = 207, 206)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.41" spread="0.69"/>
                    <measurement group_id="O2" value="-3.96" spread="0.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 52 (n = 209, 208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.16" spread="0.69"/>
                    <measurement group_id="O2" value="-6.65" spread="0.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Pulse Wave Velocity (PWV)</title>
        <description>Pulse wave velocity recordings were performed on patient while in a supine, face-up position.&#xD;
Tonometry was performed on the carotid simultaneously with the cuff inflation over the femoral artery. Two pulse wave velocity measures, meeting all quality control criteria were captured at baseline, week 12 and week 52.</description>
        <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 12 , week 52).</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Pulse Wave Velocity (PWV)</title>
          <description>Pulse wave velocity recordings were performed on patient while in a supine, face-up position.&#xD;
Tonometry was performed on the carotid simultaneously with the cuff inflation over the femoral artery. Two pulse wave velocity measures, meeting all quality control criteria were captured at baseline, week 12 and week 52.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 12 , week 52).</population>
          <units>meter/second</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to week 12 (n= 192, 196)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.68" spread="0.12"/>
                    <measurement group_id="O2" value="-0.57" spread="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to week 52 ( n= 199, 199)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.83" spread="0.13"/>
                    <measurement group_id="O2" value="0.77" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks</title>
        <description>Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.&#xD;
At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.</description>
        <time_frame>baseline, 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 52). Four patients did not have a successful CASP assessment at Week 12 but passed quality check at Week 52, thus 4 more patients were included in the Week 52 Endpoint analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks</title>
          <description>Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.&#xD;
At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoint (week 52). Four patients did not have a successful CASP assessment at Week 12 but passed quality check at Week 52, thus 4 more patients were included in the Week 52 Endpoint analysis.</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="209"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.18" spread="0.96"/>
                    <measurement group_id="O2" value="-14.70" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)</title>
        <description>At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.</description>
        <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)</title>
          <description>At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to week 12 (n=226, 222)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.84" spread="1.06"/>
                    <measurement group_id="O2" value="-14.57" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to week 52 (n=226,223)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.91" spread="0.98"/>
                    <measurement group_id="O2" value="-21.45" spread="0.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)</title>
        <description>At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, DBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.</description>
        <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)</title>
          <description>At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, DBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to week 12 (n=226, 222)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.86" spread="0.58"/>
                    <measurement group_id="O2" value="-5.58" spread="0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to week 52 (n=226,223)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.92" spread="0.57"/>
                    <measurement group_id="O2" value="-7.85" spread="0.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Sitting Pulse Pressure (msPP)</title>
        <description>Mean sitting pulse pressure for each patient and visit was calculated as the difference between the calculated values of mean sitting systolic blood pressure and mean sitting diastolic blood pressure.</description>
        <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Sitting Pulse Pressure (msPP)</title>
          <description>Mean sitting pulse pressure for each patient and visit was calculated as the difference between the calculated values of mean sitting systolic blood pressure and mean sitting diastolic blood pressure.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to week 12 (n=226,222)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.13" spread="0.82"/>
                    <measurement group_id="O2" value="-8.86" spread="0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to week 52 (n= 226, 223)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.02" spread="0.79"/>
                    <measurement group_id="O2" value="-13.58" spread="0.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Arterial Pressure (MAP)</title>
        <description>Mean arterial pressure (MAP) was calculated from mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) as (2 * msDBP + msSBP)/3.</description>
        <time_frame>baseline, 12 weeks, and 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Arterial Pressure (MAP)</title>
          <description>Mean arterial pressure (MAP) was calculated from mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) as (2 * msDBP + msSBP)/3.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to week 12 (n=226, 222)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.19" spread="0.68"/>
                    <measurement group_id="O2" value="-8.57" spread="0.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to week 52 (n=226, 223)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.92" spread="0.63"/>
                    <measurement group_id="O2" value="-12.38" spread="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP)</title>
        <description>An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maSBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.</description>
        <time_frame>Baseline, 12 weeks, and 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP)</title>
          <description>An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maSBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to week 12 (n= 164, 162)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.25" spread="0.62"/>
                    <measurement group_id="O2" value="-9.14" spread="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to week 52 (n= 174, 176)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.15" spread="0.59"/>
                    <measurement group_id="O2" value="-14.32" spread="0.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP)</title>
        <description>An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maDBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.</description>
        <time_frame>Baseline, 12 weeks, and 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP)</title>
          <description>An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maDBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to week 12 (n= 164, 162)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.44" spread="0.37"/>
                    <measurement group_id="O2" value="-5.48" spread="0.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to week 52 (n= 174, 176)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.85" spread="0.35"/>
                    <measurement group_id="O2" value="-8.44" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP)</title>
        <description>Mean 24 hour ambulatory pulse pressure was calculated as the difference between the mean 24 hour systolic and diastolic ambulatory blood pressure in corresponding visits i.e. baseline, week 12 and week 52.</description>
        <time_frame>Baseline, 12 weeks, and 52 weeks</time_frame>
        <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 (Sacubitril/Valsartan)</title>
            <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
          </group>
          <group group_id="O2">
            <title>Olmesartan</title>
            <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP)</title>
          <description>Mean 24 hour ambulatory pulse pressure was calculated as the difference between the mean 24 hour systolic and diastolic ambulatory blood pressure in corresponding visits i.e. baseline, week 12 and week 52.</description>
          <population>Full analysis set (FAS): All patients who were randomized. This endpoint included number of patients who had values at both baseline and endpoints (week 12, week 52).</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 12 (n=164, 162 )</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.77" spread="0.35"/>
                    <measurement group_id="O2" value="-3.69" spread="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to week 52 (n=174, 176)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.26" spread="0.36"/>
                    <measurement group_id="O2" value="-5.91" spread="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>LCZ696 (Sacubitril/Valsartan)</title>
          <description>Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.</description>
        </group>
        <group group_id="E2">
          <title>Olmesartan</title>
          <description>Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ANAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>COAGULOPATHY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>IRON DEFICIENCY ANAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ACUTE CORONARY SYNDROME</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>ACUTE MYOCARDIAL INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>ANGINA PECTORIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>ANGINA UNSTABLE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>ATRIAL FIBRILLATION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>CARDIO-RESPIRATORY ARREST</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>MYOCARDIAL INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>SUPRAVENTRICULAR TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>CATARACT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>INGUINAL HERNIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>CHOLECYSTITIS CHRONIC</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>CHOLELITHIASIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>APPENDICITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>DOUGLAS' ABSCESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>PERITONITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>HIP FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>PULMONARY CONTUSION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>RIB FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>ROAD TRAFFIC ACCIDENT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>SPINAL FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>SUBDURAL HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>TENDON RUPTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>UPPER LIMB FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>VASCULAR GRAFT OCCLUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>BLOOD PRESSURE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>OSTEOCHONDROSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>SQUAMOUS CELL CARCINOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>BRAIN STEM INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>ISCHAEMIC STROKE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>ATELECTASIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>PNEUMOTHORAX</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>PULMONARY EMBOLISM</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>PULMONARY PNEUMATOCELE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>RESPIRATORY FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSIVE CRISIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>ORTHOSTATIC HYPOTENSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="73" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="55" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>OEDEMA PERIPHERAL</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>INFLUENZA</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="225"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPOTENSION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="229"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="225"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Directors</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>trialandresults.registries@novartis.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01692301
org study id: CLCZ696A2216
secondary id: 2012-002899-14
nct id: NCT01692301
lead sponsor: 
has dmc: Yes
The study examined the efficacy of LCZ696 in comparison to the ARB olmesartan on Central
      Aortic Systolic Blood Pressure (CASP) and other measures of central hemodynamics and arterial
      stiffness in elderly patients with an elevated systolic blood pressure (SBP) and widened
      pulse pressure (PP).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks
time frame: baseline, 12 weeks
description: Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.
At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.
measure: Change From Baseline in Mean Central Pulse (CPP) Pressure
time frame: Baseline, 12 weeks, and 52 weeks
measure: Change From Baseline in Mean Pulse Wave Velocity (PWV)
time frame: baseline, 12 weeks, and 52 weeks
description: Pulse wave velocity recordings were performed on patient while in a supine, face-up position.
Tonometry was performed on the carotid simultaneously with the cuff inflation over the femoral artery. Two pulse wave velocity measures, meeting all quality control criteria were captured at baseline, week 12 and week 52.
measure: Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks
time frame: baseline, 52 weeks
description: Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.
At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.
measure: Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
time frame: baseline, 12 weeks, and 52 weeks
description: At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
measure: Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
time frame: baseline, 12 weeks, and 52 weeks
description: At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, DBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
measure: Change From Baseline in Mean Sitting Pulse Pressure (msPP)
time frame: baseline, 12 weeks, and 52 weeks
description: Mean sitting pulse pressure for each patient and visit was calculated as the difference between the calculated values of mean sitting systolic blood pressure and mean sitting diastolic blood pressure.
measure: Change From Baseline in Mean Arterial Pressure (MAP)
time frame: baseline, 12 weeks, and 52 weeks
description: Mean arterial pressure (MAP) was calculated from mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) as (2 * msDBP + msSBP)/3.
measure: Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP)
time frame: Baseline, 12 weeks, and 52 weeks
description: An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maSBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.
measure: Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP)
time frame: Baseline, 12 weeks, and 52 weeks
description: An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maDBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.
measure: Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP)
time frame: Baseline, 12 weeks, and 52 weeks
description: Mean 24 hour ambulatory pulse pressure was calculated as the difference between the mean 24 hour systolic and diastolic ambulatory blood pressure in corresponding visits i.e. baseline, week 12 and week 52.
arm group label: LCZ696 (sacubitril/valsartan)
arm group type: Experimental
description: Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
arm group label: Olmesartan
arm group type: Active Comparator
description: Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
intervention type: Drug
intervention name: LCZ696
description: 200 mg tablet
arm group label: LCZ696 (sacubitril/valsartan)
other name: sacubitril/valsartan
intervention type: Drug
intervention name: Olmesartan
description: 20 mg and 40 mg capsules
arm group label: Olmesartan
intervention type: Drug
intervention name: LCZ696 matching placebo
description: LCZ696 Matching Placebo tablet
arm group label: LCZ696 (sacubitril/valsartan)
arm group label: Olmesartan
intervention type: Drug
intervention name: Olmesartan matching placebo
description: Olmesartan matching placebo capsule
arm group label: LCZ696 (sacubitril/valsartan)
intervention type: Drug
intervention name: amlodipine
description: amlodipine 2.5 mg or 5 mg tablets
arm group label: LCZ696 (sacubitril/valsartan)
arm group label: Olmesartan
intervention type: Drug
intervention name: hydrochlorothiazide
description: hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets
arm group label: LCZ696 (sacubitril/valsartan)
arm group label: Olmesartan
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Argentina
country: Colombia
country: France
country: Germany
country: Greece
country: Italy
country: Japan
country: Korea, Republic of
country: Russian Federation
country: Spain
country: Taiwan
country: United States
country: Brazil
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Amlodipine
mesh term: Valsartan
mesh term: Hydrochlorothiazide
mesh term: Olmesartan
mesh term: Olmesartan Medoxomil
mesh term: Sacubitril and valsartan sodium hydrate drug combination
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certain agreements: 
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