<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/NCT01713920</url>
  </required_header>
  <id_info>
    <org_study_id>EARTH</org_study_id>
    <nct_id>NCT01713920</nct_id>
  </id_info>
  <brief_title>Efficacy and Tolerability of Combination Antihypertensive Drug in Non-Responders to ARB monoTHerapy Using 24h ABPM</brief_title>
  <acronym>EARTH</acronym>
  <official_title>Efficacy and Tolerability of Combination Antihypertensive Drug in Non-Responders to Angiotensin Receptor Blocker(ARB) monoTHerapy Using 24h ABPM.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sang Hyun Ihm, MD PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Daiichi Sankyo Korea Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Daewoong Pharmaceutical Co. LTD.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The Catholic University of Korea</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A majority of Korean doctors tend to add other antihypertensive rather than to titrate the&#xD;
      same drug.&#xD;
&#xD;
      However, we try to induce doctors to titrate the Sevikar than to add other antihypertensive&#xD;
      if patients are not controlled with Sevikar 5/20mg(amlodipine 5mg + omlesartan 20mg). As&#xD;
      above, for patients who are not controlled with Sevikar 5/20mg, doctors will proceed to other&#xD;
      prescription pattern with other choices of titration to Sevikar 5/40, 10/40mg.&#xD;
&#xD;
      It is important to evaluate BP lowering efficacy of Sevikar through the titration step in&#xD;
      patients uncontrolled with Sevikar low dose. Thus, this study is designed to demonstrate the&#xD;
      efficacy of Sevikar by titration in patients who are not controlled their BP with low dose of&#xD;
      Sevikar.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2010</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change in mean 24-hour ABPM SBP</measure>
    <time_frame>from baseline to Week 12</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>value of cuff SeSBP/SeDBP</measure>
    <time_frame>baseline, week 4, week 8 and week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in aortic PWV</measure>
    <time_frame>from baseline to week 4, week 8, week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in 24-hour ABPM DBP</measure>
    <time_frame>baseline to week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in hsCRP, HOMA-IR, MAU, Uric acid</measure>
    <time_frame>from baseline to week 12</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>SEVIKAR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who are eligible for the inclusion and exclusion criteria will be treated with Sevikar 5/20mg for 4 weeks. If subjects fail to reach the SBP threshold of SeSBP≥ 140mmHg after 4-week treatment, they will receive Sevikar 5/40mg for 4 weeks. At the end of 4-week treatment, subjects who fail to reach SBP threshold will receive Sevikar 10/40mg for 4 weeks. Subjects who can reach SBP threshold will continue to treat with current dose until 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SEVIKAR</intervention_name>
    <arm_group_label>SEVIKAR</arm_group_label>
    <other_name>amlodipine + olemsartan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female subjects &gt; 55 years&#xD;
&#xD;
          2. Subject who has consent to participate by signing on the informed consent form&#xD;
&#xD;
          3. Uncontrolled hypertensive patients defined as:&#xD;
&#xD;
               -  Uncontrolled hypertensive: subjects who are mean SBP ≥ 140 mmHg after being&#xD;
                  treated with ARB(Valsartan 80mg or Candesartan 8mg) monotherapy during at least 4&#xD;
                  weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Secondary hypertension&#xD;
&#xD;
          2. SeSBP ≥ 180mmHg&#xD;
&#xD;
          3. SeSBP difference ≥ 20mmHg or SeDBP difference ≥ 10mmHg&#xD;
&#xD;
          4. A history of hypertensive encephalopathy, unstable angina, transient ischemic attack,&#xD;
             MI, or any type of revascularization procedure within the last 6 months&#xD;
&#xD;
          5. Heart failure, second- or third-degree heart block, significant arrhythmia or valvular&#xD;
             heart disease&#xD;
&#xD;
          6. Significant cardiovascular, cerebrovascular, renal, gastrointestinal, or hematologic&#xD;
             disease, at the discretion of investigator&#xD;
&#xD;
          7. Creatinine clearance&lt;20mL/min and Renal artery stenosis, Renal Transplantation,&#xD;
             Patients with only one kidney&#xD;
&#xD;
          8. Evidence of liver disease as indicated by alanine transaminase (ALT) and aspartate&#xD;
             transaminase (AST) and/or total bilirubin ≥ 3 × the upper limit of normal (ULN)&#xD;
&#xD;
          9. Hyperkalemia (&gt;5.5mmol/L)&#xD;
&#xD;
         10. Patients with sodium depletion is not correct or Patients with fluid depletion is not&#xD;
             correct&#xD;
&#xD;
         11. Chronic inflammation&#xD;
&#xD;
         12. Patients with severe eye-related disorders (Retinal bleeding within 6 months,&#xD;
             Blindness, Hypertension complications with Retinal micro-aneurysms)&#xD;
&#xD;
         13. Diabetes mellitus&#xD;
&#xD;
         14. Hematologic/oncologic, neurologic and psychiatric diseases&#xD;
&#xD;
         15. Females who were pregnant, breastfeeding, planning a pregnancy or who were of&#xD;
             childbearing potential&#xD;
&#xD;
         16. Contraindications for amlodipine, losartan, olmesartan medoxomil, or other ARBs&#xD;
&#xD;
         17. With known allergic reaction, lack of response or contraindication to Angiotensin II&#xD;
             receptor antagonists&#xD;
&#xD;
         18. Mean DBP &gt; 110 mmHg&#xD;
&#xD;
         19. Patients who took antihyperlipidemic agents within 30 days&#xD;
&#xD;
         20. Subject who have participated in other clinical trial within the last one month&#xD;
&#xD;
         21. Any subjects who are unable to cooperate with protocol requirements and follow-up&#xD;
             procedures or who are in medical condition that is not eligible to be entered in&#xD;
             investigators' discretion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The Catholic University of Korea Bucheon St. Mary's Hospital</name>
      <address>
        <city>Bucheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea Seoul St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Korean National Health &amp; Nutrition Examination Surveys. Available from: URL://http://knhanes.cdc.go.kr/</citation>
  </reference>
  <reference>
    <citation>Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998 Jun 13;351(9118):1755-62. doi: 10.1016/s0140-6736(98)04311-6.</citation>
    <PMID>9635947</PMID>
  </reference>
  <reference>
    <citation>ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002 Dec 18;288(23):2998-3007. doi: 10.1001/jama.288.23.2998.</citation>
    <PMID>12479764</PMID>
  </reference>
  <reference>
    <citation>Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J; ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005 Sep 10-16;366(9489):895-906. doi: 10.1016/S0140-6736(05)67185-1.</citation>
    <PMID>16154016</PMID>
  </reference>
  <reference>
    <citation>Poulter NR, Wedel H, Dahlof B, Sever PS, Beevers DG, Caulfield M, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J, Pocock S; ASCOT Investigators. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet. 2005 Sep 10-16;366(9489):907-13. doi: 10.1016/S0140-6736(05)67186-3.</citation>
    <PMID>16154017</PMID>
  </reference>
  <reference>
    <citation>Chrysant SG, Melino M, Karki S, Lee J, Heyrman R. The combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, placebo-controlled, 8-week factorial efficacy and safety study. Clin Ther. 2008 Apr;30(4):587-604. doi: 10.1016/j.clinthera.2008.04.002.</citation>
    <PMID>18498909</PMID>
  </reference>
  <reference>
    <citation>Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72. doi: 10.1001/jama.289.19.2560. Epub 2003 May 14. Erratum In: JAMA. 2003 Jul 9;290(2):197.</citation>
    <PMID>12748199</PMID>
  </reference>
  <reference>
    <citation>Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007 Jun;25(6):1105-87. doi: 10.1097/HJH.0b013e3281fc975a. No abstract available. Erratum In: J Hypertens. 2007 Aug;25(8):1749.</citation>
    <PMID>17563527</PMID>
  </reference>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <last_update_submitted>November 6, 2015</last_update_submitted>
  <last_update_submitted_qc>November 6, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 10, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>The Catholic University of Korea</investigator_affiliation>
    <investigator_full_name>Sang Hyun Ihm, MD PhD</investigator_full_name>
    <investigator_title>Associate Professor , Division of Cardiology, Department of Internal Medicine</investigator_title>
  </responsible_party>
  <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>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01713920
org study id: EARTH
nct id: NCT01713920
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
A majority of Korean doctors tend to add other antihypertensive rather than to titrate the
      same drug.

      However, we try to induce doctors to titrate the Sevikar than to add other antihypertensive
      if patients are not controlled with Sevikar 5/20mg(amlodipine 5mg + omlesartan 20mg). As
      above, for patients who are not controlled with Sevikar 5/20mg, doctors will proceed to other
      prescription pattern with other choices of titration to Sevikar 5/40, 10/40mg.

      It is important to evaluate BP lowering efficacy of Sevikar through the titration step in
      patients uncontrolled with Sevikar low dose. Thus, this study is designed to demonstrate the
      efficacy of Sevikar by titration in patients who are not controlled their BP with low dose of
      Sevikar.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: change in mean 24-hour ABPM SBP
time frame: from baseline to Week 12
measure: value of cuff SeSBP/SeDBP
time frame: baseline, week 4, week 8 and week 12
measure: change in aortic PWV
time frame: from baseline to week 4, week 8, week 12
measure: change in 24-hour ABPM DBP
time frame: baseline to week 12
measure: change in hsCRP, HOMA-IR, MAU, Uric acid
time frame: from baseline to week 12
arm group label: SEVIKAR
arm group type: Experimental
description: Subjects who are eligible for the inclusion and exclusion criteria will be treated with Sevikar 5/20mg for 4 weeks. If subjects fail to reach the SBP threshold of SeSBP≥ 140mmHg after 4-week treatment, they will receive Sevikar 5/40mg for 4 weeks. At the end of 4-week treatment, subjects who fail to reach SBP threshold will receive Sevikar 10/40mg for 4 weeks. Subjects who can reach SBP threshold will continue to treat with current dose until 12 weeks.
intervention type: Drug
intervention name: SEVIKAR
arm group label: SEVIKAR
other name: amlodipine + olemsartan
criteria: 
gender: All
minimum age: 55 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: Korea, Republic of
citation: Korean National Health & Nutrition Examination Surveys. Available from: URL://http://knhanes.cdc.go.kr/
citation: Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998 Jun 13;351(9118):1755-62. doi: 10.1016/s0140-6736(98)04311-6.
PMID: 9635947
citation: ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002 Dec 18;288(23):2998-3007. doi: 10.1001/jama.288.23.2998.
PMID: 12479764
citation: Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J; ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005 Sep 10-16;366(9489):895-906. doi: 10.1016/S0140-6736(05)67185-1.
PMID: 16154016
citation: Poulter NR, Wedel H, Dahlof B, Sever PS, Beevers DG, Caulfield M, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J, Pocock S; ASCOT Investigators. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet. 2005 Sep 10-16;366(9489):907-13. doi: 10.1016/S0140-6736(05)67186-3.
PMID: 16154017
citation: Chrysant SG, Melino M, Karki S, Lee J, Heyrman R. The combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, placebo-controlled, 8-week factorial efficacy and safety study. Clin Ther. 2008 Apr;30(4):587-604. doi: 10.1016/j.clinthera.2008.04.002.
PMID: 18498909
citation: Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72. doi: 10.1001/jama.289.19.2560. Epub 2003 May 14. Erratum In: JAMA. 2003 Jul 9;290(2):197.
PMID: 12748199
citation: Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007 Jun;25(6):1105-87. doi: 10.1097/HJH.0b013e3281fc975a. No abstract available. Erratum In: J Hypertens. 2007 Aug;25(8):1749.
PMID: 17563527
responsible party type: Sponsor-Investigator
investigator affiliation: The Catholic University of Korea
investigator full name: Sang Hyun Ihm, MD PhD
investigator title: Associate Professor , Division of Cardiology, Department of Internal Medicine
mesh term: Hypertension
mesh term: Amlodipine