Efficacy and Tolerability of Combination Antihypertensive Drug in Non-Responders to Angiotensin Receptor Blocker(ARB) monoTHerapy Using 24h ABPM - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hypertension	Drug: SEVIKAR	Phase 4

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment

Resource links provided by NLM:

MedlinePlus related topics: Blood Pressure Medicines High Blood Pressure

U.S. FDA Resources

Further study details as provided by The Catholic University of Korea:

Primary Outcome Measures:

change in mean 24-hour ABPM SBP [ Time Frame: from baseline to Week 12 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

value of cuff SeSBP/SeDBP [ Time Frame: baseline, week 4, week 8 and week 12 ] [ Designated as safety issue: Yes ]
change in aortic PWV [ Time Frame: from baseline to week 4, week 8, week 12 ] [ Designated as safety issue: No ]
change in 24-hour ABPM DBP [ Time Frame: baseline to week 12 ] [ Designated as safety issue: Yes ]
change in hsCRP, HOMA-IR, MAU, Uric acid [ Time Frame: from baseline to week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment:	68
Study Start Date:	April 2010
Estimated Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: SEVIKAR 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.	Drug: SEVIKAR Other Name: amlodipine + olemsartan

Arms

Assigned Interventions

Experimental: SEVIKAR

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.

Drug: SEVIKAR

Other Name: amlodipine + olemsartan

Eligibility

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female subjects > 55 years
Subject who has consent to participate by signing on the informed consent form
Uncontrolled hypertensive patients defined as:
- Uncontrolled hypertensive: subjects who are mean SBP ≥ 140 mmHg after being treated with ARB(Valsartan 80mg or Candesartan 8mg) monotherapy during at least 4 weeks.

Exclusion Criteria:

Secondary hypertension
SeSBP ≥ 180mmHg
SeSBP difference ≥ 20mmHg or SeDBP difference ≥ 10mmHg
A history of hypertensive encephalopathy, unstable angina, transient ischemic attack, MI, or any type of revascularization procedure within the last 6 months
Heart failure, second- or third-degree heart block, significant arrhythmia or valvular heart disease
Significant cardiovascular, cerebrovascular, renal, gastrointestinal, or hematologic disease, at the discretion of investigator
Creatinine clearance<20mL/min and Renal artery stenosis, Renal Transplantation, Patients with only one kidney
Evidence of liver disease as indicated by alanine transaminase (ALT) and aspartate transaminase (AST) and/or total bilirubin ≥ 3 × the upper limit of normal (ULN)
Hyperkalemia (>5.5mmol/L)
Patients with sodium depletion is not correct or Patients with fluid depletion is not correct
Chronic inflammation
Patients with severe eye-related disorders (Retinal bleeding within 6 months, Blindness, Hypertension complications with Retinal micro-aneurysms)
Diabetes mellitus
Hematologic/oncologic, neurologic and psychiatric diseases
Females who were pregnant, breastfeeding, planning a pregnancy or who were of childbearing potential
Contraindications for amlodipine, losartan, olmesartan medoxomil, or other ARBs
With known allergic reaction, lack of response or contraindication to Angiotensin II receptor antagonists
Mean DBP > 110 mmHg
Patients who took antihyperlipidemic agents within 30 days
Subject who have participated in other clinical trial within the last one month
Any subjects who are unable to cooperate with protocol requirements and follow-up procedures or who are in medical condition that is not eligible to be entered in investigators' discretion

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01713920

Contacts

Contact: Ho-Joong Youn, M.D.,Ph.D.

younhj@catholic.ac.kr

Locations

Korea, Republic of
The Catholic University of Korea Bucheon St. Mary's Hospital	Recruiting
Bucheon, Korea, Republic of
Contact: Sang-Hyun Ihm, M.D.,Ph.D.
The Catholic University of Korea Seoul St. Mary's Hospital	Recruiting
Seoul, Korea, Republic of
Contact: Ho-Joong Youn, M.D.,Ph.D.

Sponsors and Collaborators

Sang Hyun Ihm

Daiichi Sankyo Korea Co., Ltd.

Daewoong Pharmaceutical Co. LTD.

More Information

Publications:

Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, Ménard 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.

[No authors listed] 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.

Dahlöf 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.

Poulter NR, Wedel H, Dahlöf 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.

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.

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. Epub 2003 May 14. Erratum in: JAMA. 2003 Jul 9;290(2):197.

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. No abstract available. Erratum in: J Hypertens. 2007 Aug;25(8):1749.

Responsible Party:	Sang Hyun Ihm, Associate Professor , Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea
ClinicalTrials.gov Identifier:	NCT01713920 History of Changes
Other Study ID Numbers:	EARTH
Study First Received:	October 22, 2012
Last Updated:	October 24, 2012
Health Authority:	Korea: Food and Drug Administration

Additional relevant MeSH terms:

Hypertension
Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
Angiotensin Receptor Antagonists

Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013

Efficacy and Tolerability of Combination Antihypertensive Drug in Non-Responders to Angiotensin Receptor Blocker(ARB) monoTHerapy Using 24h ABPM (EARTH)