<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/NCT01669928</url>
  </required_header>
  <id_info>
    <org_study_id>CRO1749</org_study_id>
    <nct_id>NCT01669928</nct_id>
  </id_info>
  <brief_title>Anti-hypertensive Medication Dosing Regimen in Effective Blood Pressure Control</brief_title>
  <acronym>HARMONY</acronym>
  <official_title>Hellenic Anglo Research Into Morning Or Evening Antihypertensive Drug deliverY Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aristotle University Of Thessaloniki</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomised crossover trial of anti-hypertensive medication dosing regimen in effective&#xD;
      blood pressure control.&#xD;
&#xD;
      To investigate whether there is a difference in 24 hour blood pressure (BP) control when&#xD;
      antihypertensive medications are taken in the morning compared with the evening.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The identification of any significant difference could lead to more effective therapeutic&#xD;
      management of arterial hypertension, which in turn would result in a reduced cardiovascular&#xD;
      burden, lower costs and a better quality of life for hypertensive patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2012</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in 24 Hour Systolic Blood Pressure</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in 24 hour systolic Blood Pressure using ABPM</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Day-time ABPM Systolic BP</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Day-time ABPM Diastolic BP</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Μean Night Time ABPM Systolic BP</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Μean Night Time ABPM Diastolic BP</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Clinic - Systolic BP</measure>
    <time_frame>6 months</time_frame>
    <description>This measure was assessed at a clinic.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Clinic - Diastolic BP</measure>
    <time_frame>6 months</time_frame>
    <description>This measure was assessed at a clinic.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self Reported Side Effects</measure>
    <time_frame>12 months</time_frame>
    <description>Serious Adverse Events reported during the trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Score</measure>
    <time_frame>6 months</time_frame>
    <description>Quality of Life Score via questionnaire - EQ-5D-5L Score scale is 0-100, 100 optimal health state.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">103</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Evening medication</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Morning medication</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Antihypertensive medication in the morning(between 06.00 and 11.00)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-hypertensive Medication -</intervention_name>
    <description>Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication.&#xD;
Dosing regimen either in the morning (between 06.00 and 11.00) or in the evening (between 18.00 and 23.00).</description>
    <arm_group_label>Evening medication</arm_group_label>
    <arm_group_label>Morning medication</arm_group_label>
    <other_name>PR1 Diruetics</other_name>
    <other_name>PR3 Beta Blockers</other_name>
    <other_name>PR4 Calcium channel blockers</other_name>
    <other_name>PR5 ACE inhibitors</other_name>
    <other_name>PR6 Angiotensin II Receptor Blockers</other_name>
    <other_name>PR7 Centrally acting agents</other_name>
    <other_name>PR8 Alpha blockers</other_name>
    <other_name>PR9 Direct Renin Inhibitors</other_name>
    <other_name>PR10 Vasodilators</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Caucasian patients aged 18-80 years;&#xD;
&#xD;
          -  History of any grade of hypertension for at least 1 year, including at least 3 months&#xD;
             of constant antihypertensive medication (consisting of ≥ 1 antihypertensive drugs,&#xD;
             each administered in one dose daily), with reasonably controlled BP (≤150/90 mmHg and&#xD;
             ≥ 115/75 mmHg on usual medication) based on previous clinic records, in the last 3&#xD;
             months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BP levels &gt; 150/90 mmHg or &lt; 115/75 mmHg in the last 3 months.&#xD;
&#xD;
          -  Postural hypotension, defined as symptoms resulting from a &gt; 20 mm Hg drop of systolic&#xD;
             BP or a &gt; 10 mm Hg drop of diastolic BP or both between 1 and 3 min after standing&#xD;
             from the sitting position.&#xD;
&#xD;
          -  Known Extreme dippers at baseline (fall of mean night time SBP &gt; 20% of mean day time&#xD;
             SBP)&#xD;
&#xD;
          -  Individuals with jobs which require night-time shift work.&#xD;
&#xD;
          -  Pregnant women or those planning to become pregnant.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Neil Poulter, MRCS LRCP MBBS MRCP MSc FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aristotle University of Thessaloniki</name>
      <address>
        <city>Thessaloniki</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial Clinical Trials Unit</name>
      <address>
        <city>London</city>
        <zip>W2 1LA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Lemmer B. Clinical chronopharmacology: the importance of time in drug treatment. Ciba Found Symp. 1995;183:235-47; discussion 247-53. doi: 10.1002/9780470514597.ch13.</citation>
    <PMID>7656688</PMID>
  </reference>
  <reference>
    <citation>Bruguerolle B. Chronopharmacokinetics. Current status. Clin Pharmacokinet. 1998 Aug;35(2):83-94. doi: 10.2165/00003088-199835020-00001.</citation>
    <PMID>9739478</PMID>
  </reference>
  <reference>
    <citation>Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010 Mar 13;375(9718):895-905. doi: 10.1016/S0140-6736(10)60308-X.</citation>
    <PMID>20226988</PMID>
  </reference>
  <reference>
    <citation>Smolensky MH, Hermida RC, Ayala DE, Tiseo R, Portaluppi F. Administration-time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension. Blood Press Monit. 2010 Aug;15(4):173-80. doi: 10.1097/MBP.0b013e32833c7308.</citation>
    <PMID>20571367</PMID>
  </reference>
  <reference>
    <citation>Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010 Sep;27(8):1629-51. doi: 10.3109/07420528.2010.510230.</citation>
    <PMID>20854139</PMID>
  </reference>
  <reference>
    <citation>Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301. Erratum In: 2000 May 4;342(18):1376. N Engl J Med 2000 Mar 9;342(10):748.</citation>
    <PMID>10639539</PMID>
  </reference>
  <reference>
    <citation>Mayet J, Chapman N, Li CK, Shahi M, Poulter NR, Sever PS, Foale RA, Thom SA. Ethnic differences in the hypertensive heart and 24-hour blood pressure profile. Hypertension. 1998 May;31(5):1190-4. doi: 10.1161/01.hyp.31.5.1190.</citation>
    <PMID>9576134</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>July 2, 2012</study_first_submitted>
  <study_first_submitted_qc>August 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <results_first_submitted>April 29, 2019</results_first_submitted>
  <results_first_submitted_qc>March 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 8, 2021</results_first_posted>
  <last_update_submitted>March 5, 2021</last_update_submitted>
  <last_update_submitted_qc>March 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hypertension</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>Antihypertensive Agents</mesh_term>
    <mesh_term>Calcium Channel Blockers</mesh_term>
    <mesh_term>Angiotensin II</mesh_term>
    <mesh_term>Angiotensin-Converting Enzyme Inhibitors</mesh_term>
    <mesh_term>Angiotensin Receptor Antagonists</mesh_term>
    <mesh_term>Renin Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Morning Medication, Then Evening</title>
          <description>Antihypertensive medication in the morning (between 06.00 and 11.00) for 6 months, then cross over to antihypertensive medication in the evening (between 18.00 and 23.00) for 6 months.&#xD;
Anti-hypertensive Medication -: Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication.</description>
        </group>
        <group group_id="P2">
          <title>Evening Medication, Then Morning</title>
          <description>Anti hypertensive medication in the evening (between 18.00 and 23.00) for 6 months, then cross over to antihypertensive medication in the morning (between 06.00 and 11.00) for 6 months,&#xD;
Anti-hypertensive Medication -: Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Second Intervention</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Morning Medication, Then Evening</title>
          <description>Antihypertensive medication in the morning (between 06.00 and 11.00) for 6 months, then cross over to antihypertensive medication in the evening (between 18.00 and 23.00) for 6 months.&#xD;
Anti-hypertensive Medication -: Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication.</description>
        </group>
        <group group_id="B2">
          <title>Evening Medication, Then Morning</title>
          <description>Anti hypertensive medication in the evening (between 18.00 and 23.00) for 6 months, then cross over to antihypertensive medication in the morning (between 06.00 and 11.00) for 6 months,&#xD;
Anti-hypertensive Medication -: Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication.</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="51"/>
            <count group_id="B2" value="52"/>
            <count group_id="B3" value="103"/>
          </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="61.8" spread="11"/>
                    <measurement group_id="B2" value="62.8" spread="9.7"/>
                    <measurement group_id="B3" value="61.8" spread="10.3"/>
                  </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="24"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="103"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Greece</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Changes in 24 Hour Systolic Blood Pressure</title>
        <description>Changes in 24 hour systolic Blood Pressure using ABPM</description>
        <time_frame>6 months</time_frame>
        <population>Total of 8 withdrawals / drop outs</population>
        <group_list>
          <group group_id="O1">
            <title>Morning Medication</title>
            <description>Antihypertensive medication in the morning (between 06.00 and 11.00)</description>
          </group>
          <group group_id="O2">
            <title>Evening Medication</title>
            <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in 24 Hour Systolic Blood Pressure</title>
          <description>Changes in 24 hour systolic Blood Pressure using ABPM</description>
          <population>Total of 8 withdrawals / drop outs</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="95"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="129.65" spread="10.66"/>
                    <measurement group_id="O2" value="129.75" spread="12.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Day-time ABPM Systolic BP</title>
        <time_frame>6 months</time_frame>
        <population>Total of 8 withdrawals / drop outs</population>
        <group_list>
          <group group_id="O1">
            <title>Morning Medication</title>
            <description>Antihypertensive medication in the morning (between 06.00 and 11.00)</description>
          </group>
          <group group_id="O2">
            <title>Evening Medication</title>
            <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Day-time ABPM Systolic BP</title>
          <population>Total of 8 withdrawals / drop outs</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="132.24" spread="10.86"/>
                    <measurement group_id="O2" value="132.77" spread="12.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Day-time ABPM Diastolic BP</title>
        <time_frame>6 months</time_frame>
        <population>Total of 8 withdrawals / drop outs</population>
        <group_list>
          <group group_id="O1">
            <title>Morning Medication</title>
            <description>Antihypertensive medication in the morning (between 06.00 and 11.00)</description>
          </group>
          <group group_id="O2">
            <title>Evening Medication</title>
            <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Day-time ABPM Diastolic BP</title>
          <population>Total of 8 withdrawals / drop outs</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.27" spread="7.73"/>
                    <measurement group_id="O2" value="80.55" spread="8.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Μean Night Time ABPM Systolic BP</title>
        <time_frame>6 months</time_frame>
        <population>Total of 8 withdrawals / drop outs</population>
        <group_list>
          <group group_id="O1">
            <title>Morning Medication</title>
            <description>Antihypertensive medication in the morning (between 06.00 and 11.00)</description>
          </group>
          <group group_id="O2">
            <title>Evening Medication</title>
            <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
          </group>
        </group_list>
        <measure>
          <title>Μean Night Time ABPM Systolic BP</title>
          <population>Total of 8 withdrawals / drop outs</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="122.76" spread="12.18"/>
                    <measurement group_id="O2" value="121.08" spread="14.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Μean Night Time ABPM Diastolic BP</title>
        <time_frame>6 months</time_frame>
        <population>Total of 8 withdrawals / drop outs</population>
        <group_list>
          <group group_id="O1">
            <title>Morning Medication</title>
            <description>Antihypertensive medication in the morning (between 06.00 and 11.00)</description>
          </group>
          <group group_id="O2">
            <title>Evening Medication</title>
            <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
          </group>
        </group_list>
        <measure>
          <title>Μean Night Time ABPM Diastolic BP</title>
          <population>Total of 8 withdrawals / drop outs</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.92" spread="9.68"/>
                    <measurement group_id="O2" value="70.57" spread="9.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Clinic - Systolic BP</title>
        <description>This measure was assessed at a clinic.</description>
        <time_frame>6 months</time_frame>
        <population>Total of 8 withdrawals / drop outs</population>
        <group_list>
          <group group_id="O1">
            <title>Morning Medication</title>
            <description>Antihypertensive medication in the morning (between 06.00 and 11.00)</description>
          </group>
          <group group_id="O2">
            <title>Evening Medication</title>
            <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Clinic - Systolic BP</title>
          <description>This measure was assessed at a clinic.</description>
          <population>Total of 8 withdrawals / drop outs</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="129.37" spread="11.21"/>
                    <measurement group_id="O2" value="129.81" spread="12.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Clinic - Diastolic BP</title>
        <description>This measure was assessed at a clinic.</description>
        <time_frame>6 months</time_frame>
        <population>Total of 8 withdrawals / drop outs</population>
        <group_list>
          <group group_id="O1">
            <title>Morning Medication</title>
            <description>Antihypertensive medication in the morning (between 06.00 and 11.00)</description>
          </group>
          <group group_id="O2">
            <title>Evening Medication</title>
            <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Clinic - Diastolic BP</title>
          <description>This measure was assessed at a clinic.</description>
          <population>Total of 8 withdrawals / drop outs</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.26" spread="7.12"/>
                    <measurement group_id="O2" value="77.41" spread="8.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Self Reported Side Effects</title>
        <description>Serious Adverse Events reported during the trial</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Morning Medication</title>
            <description>Antihypertensive medication in the morning (between 06.00 and 11.00) for 6 months&#xD;
Anti-hypertensive Medication -: Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication.</description>
          </group>
          <group group_id="O2">
            <title>Evening Medication</title>
            <description>Anti hypertensive medication in the evening&#xD;
Anti-hypertensive Medication -: Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Self Reported Side Effects</title>
          <description>Serious Adverse Events reported during the trial</description>
          <units>Serious Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Quality of Life Score</title>
        <description>Quality of Life Score via questionnaire - EQ-5D-5L Score scale is 0-100, 100 optimal health state.</description>
        <time_frame>6 months</time_frame>
        <population>Total of 8 withdrawals / drop outs</population>
        <group_list>
          <group group_id="O1">
            <title>Morning Medication</title>
            <description>Antihypertensive medication in the morning (between 06.00 and 11.00)</description>
          </group>
          <group group_id="O2">
            <title>Evening Medication</title>
            <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Life Score</title>
          <description>Quality of Life Score via questionnaire - EQ-5D-5L Score scale is 0-100, 100 optimal health state.</description>
          <population>Total of 8 withdrawals / drop outs</population>
          <units>Score out of 100</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.14" spread="11.45"/>
                    <measurement group_id="O2" value="84.04" spread="10.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Morning Medication</title>
          <description>Antihypertensive medication in the morning (between 06.00 and 11.00)</description>
        </group>
        <group group_id="E2">
          <title>Evening Medication</title>
          <description>Anti hypertensive medication in the evening (between 18.00 and 23.00)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope episode</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Planned admission for ERCP with stent.</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="95"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Professor Neil Poulter</name_or_title>
      <organization>Imperial College London</organization>
      <phone>+44 20 7594 3446</phone>
      <email>n.poulter@imperial.ac.uk</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/NCT01669928
org study id: CRO1749
nct id: NCT01669928
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A randomised crossover trial of anti-hypertensive medication dosing regimen in effective
      blood pressure control.

      To investigate whether there is a difference in 24 hour blood pressure (BP) control when
      antihypertensive medications are taken in the morning compared with the evening.
The identification of any significant difference could lead to more effective therapeutic
      management of arterial hypertension, which in turn would result in a reduced cardiovascular
      burden, lower costs and a better quality of life for hypertensive patients.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes in 24 Hour Systolic Blood Pressure
time frame: 6 months
description: Changes in 24 hour systolic Blood Pressure using ABPM
measure: Mean Day-time ABPM Systolic BP
time frame: 6 months
measure: Mean Day-time ABPM Diastolic BP
time frame: 6 months
measure: Μean Night Time ABPM Systolic BP
time frame: 6 months
measure: Μean Night Time ABPM Diastolic BP
time frame: 6 months
measure: Mean Clinic - Systolic BP
time frame: 6 months
description: This measure was assessed at a clinic.
measure: Mean Clinic - Diastolic BP
time frame: 6 months
description: This measure was assessed at a clinic.
measure: Self Reported Side Effects
time frame: 12 months
description: Serious Adverse Events reported during the trial
measure: Quality of Life Score
time frame: 6 months
description: Quality of Life Score via questionnaire - EQ-5D-5L Score scale is 0-100, 100 optimal health state.
arm group label: Evening medication
arm group type: Active Comparator
description: Anti hypertensive medication in the evening (between 18.00 and 23.00)
arm group label: Morning medication
arm group type: Active Comparator
description: Antihypertensive medication in the morning(between 06.00 and 11.00)
intervention type: Drug
intervention name: Anti-hypertensive Medication -
description: Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication.
Dosing regimen either in the morning (between 06.00 and 11.00) or in the evening (between 18.00 and 23.00).
arm group label: Evening medication
arm group label: Morning medication
other name: PR1 Diruetics
other name: PR3 Beta Blockers
other name: PR4 Calcium channel blockers
other name: PR5 ACE inhibitors
other name: PR6 Angiotensin II Receptor Blockers
other name: PR7 Centrally acting agents
other name: PR8 Alpha blockers
other name: PR9 Direct Renin Inhibitors
other name: PR10 Vasodilators
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Neil Poulter, MRCS LRCP MBBS MRCP MSc FRCP
role: Principal Investigator
affiliation: Imperial College London
facility: 
facility: 
country: Greece
country: United Kingdom
citation: Lemmer B. Clinical chronopharmacology: the importance of time in drug treatment. Ciba Found Symp. 1995;183:235-47; discussion 247-53. doi: 10.1002/9780470514597.ch13.
PMID: 7656688
citation: Bruguerolle B. Chronopharmacokinetics. Current status. Clin Pharmacokinet. 1998 Aug;35(2):83-94. doi: 10.2165/00003088-199835020-00001.
PMID: 9739478
citation: Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010 Mar 13;375(9718):895-905. doi: 10.1016/S0140-6736(10)60308-X.
PMID: 20226988
citation: Smolensky MH, Hermida RC, Ayala DE, Tiseo R, Portaluppi F. Administration-time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension. Blood Press Monit. 2010 Aug;15(4):173-80. doi: 10.1097/MBP.0b013e32833c7308.
PMID: 20571367
citation: Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010 Sep;27(8):1629-51. doi: 10.3109/07420528.2010.510230.
PMID: 20854139
citation: Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301. Erratum In: 2000 May 4;342(18):1376. N Engl J Med 2000 Mar 9;342(10):748.
PMID: 10639539
citation: Mayet J, Chapman N, Li CK, Shahi M, Poulter NR, Sever PS, Foale RA, Thom SA. Ethnic differences in the hypertensive heart and 24-hour blood pressure profile. Hypertension. 1998 May;31(5):1190-4. doi: 10.1161/01.hyp.31.5.1190.
PMID: 9576134
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Antihypertensive Agents
mesh term: Calcium Channel Blockers
mesh term: Angiotensin II
mesh term: Angiotensin-Converting Enzyme Inhibitors
mesh term: Angiotensin Receptor Antagonists
mesh term: Renin Inhibitors
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 