Renin Profiling in Selection of Initial Antihypertensive Drug - Full Text View

Purpose

The purpose of this research study is to determine whether a simple blood test measuring a hormone called renin can better determine which first drug would be most effective in controlling blood pressure, in comparison with the more traditional approach recommended by JNC7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure).

Condition	Intervention
Hypertension	Drug: olmesartan, hydrochlorothiazide, amlodipine Drug: hydrochlorothiazide (HCTZ) or olmesartan


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Clinical Trial of Renin Profiling in Selection of Initial Antihypertensive Drug

Resource links provided by NLM:

MedlinePlus related topics: Blood Pressure Medicines

Drug Information available for: Hydrochlorothiazide Amlodipine Amlodipine besylate Olmesartan Olmesartan medoxomil

U.S. FDA Resources

Further study details as provided by The Louis & Rachel Rudin Foundation:

Primary Outcome Measures:

Percent of patients with BP <140/90 mmHg and on monotherapy at the 5th visit. [ Time Frame: 3-4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Will include change in blood pressure, percent of patients with blood pressure <140/mmHg, total number of classes of antihypertensive agents taken, adverse events and discontinuation of therapy. [ Time Frame: 3-4 months ] [ Designated as safety issue: No ]
In addition, we will be able to determine the reproducibility of PRA determination in this clinical setting. Finally, it will be possible to demonstrate the value of "in-treatment" PRA as a guide to treatment modification. [ Time Frame: 3-4 months ] [ Designated as safety issue: No ]


Enrollment:	185
Study Start Date:	December 2005
Study Completion Date:	October 2011
Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HCTZ , ARB Patients randomized to the Experimental Arm have initial drug choice determined by Plasma Renin Activity level. Low renin subjects are assigned to the diuretic hydrochlorothothiazide. Those with PRA >.65 ng/hr are assigned to the angiotensin receptor blocker, olmesartan.	Drug: olmesartan, hydrochlorothiazide, amlodipine hydrochlorothiazide (HCTZ) 25mg OD, increased to 50 mg OD at 3 weeks. Olmesartan 20 mg OD, to be increased to 40 mg at 3 weeks. Amlodipine 5 mg, may be added at 6 weeks, if BP >140 mmHg Other Name: Renin guided selection of treatment Drug: hydrochlorothiazide (HCTZ) or olmesartan HCTZ 25 mg, increasing to 50 mg at 3-4 weeks or Olmesartan 20 mg, increasing to 40 mg at 3-4 weeks. If blood pressure >140/90 mmHg at 6 weeks, amlodipine 5 mg may be added Other Name: Standard Therapy
Active Comparator: Conventional antihypertensive therapy All patients randomized to Active Comparator Arm received hydrochlorothiazide 25 mg, which is increased to 50 mg at 3-4 weeks. At 6 weeks, olmesartan may be added if BP > 140 mmHg	Drug: olmesartan, hydrochlorothiazide, amlodipine hydrochlorothiazide (HCTZ) 25mg OD, increased to 50 mg OD at 3 weeks. Olmesartan 20 mg OD, to be increased to 40 mg at 3 weeks. Amlodipine 5 mg, may be added at 6 weeks, if BP >140 mmHg Other Name: Renin guided selection of treatment Drug: hydrochlorothiazide (HCTZ) or olmesartan HCTZ 25 mg, increasing to 50 mg at 3-4 weeks or Olmesartan 20 mg, increasing to 40 mg at 3-4 weeks. If blood pressure >140/90 mmHg at 6 weeks, amlodipine 5 mg may be added Other Name: Standard Therapy

Arms

Assigned Interventions

Experimental: HCTZ , ARB

Patients randomized to the Experimental Arm have initial drug choice determined by Plasma Renin Activity level. Low renin subjects are assigned to the diuretic hydrochlorothothiazide. Those with PRA >.65 ng/hr are assigned to the angiotensin receptor blocker, olmesartan.

Drug: olmesartan, hydrochlorothiazide, amlodipine

hydrochlorothiazide (HCTZ) 25mg OD, increased to 50 mg OD at 3 weeks. Olmesartan 20 mg OD, to be increased to 40 mg at 3 weeks. Amlodipine 5 mg, may be added at 6 weeks, if BP >140 mmHg

Other Name: Renin guided selection of treatment

Drug: hydrochlorothiazide (HCTZ) or olmesartan

HCTZ 25 mg, increasing to 50 mg at 3-4 weeks or Olmesartan 20 mg, increasing to 40 mg at 3-4 weeks. If blood pressure >140/90 mmHg at 6 weeks, amlodipine 5 mg may be added

Other Name: Standard Therapy

Active Comparator: Conventional antihypertensive therapy

All patients randomized to Active Comparator Arm received hydrochlorothiazide 25 mg, which is increased to 50 mg at 3-4 weeks. At 6 weeks, olmesartan may be added if BP > 140 mmHg

Drug: olmesartan, hydrochlorothiazide, amlodipine

hydrochlorothiazide (HCTZ) 25mg OD, increased to 50 mg OD at 3 weeks. Olmesartan 20 mg OD, to be increased to 40 mg at 3 weeks. Amlodipine 5 mg, may be added at 6 weeks, if BP >140 mmHg

Other Name: Renin guided selection of treatment

Drug: hydrochlorothiazide (HCTZ) or olmesartan

HCTZ 25 mg, increasing to 50 mg at 3-4 weeks or Olmesartan 20 mg, increasing to 40 mg at 3-4 weeks. If blood pressure >140/90 mmHg at 6 weeks, amlodipine 5 mg may be added

Other Name: Standard Therapy

Detailed Description:

Hypothesis: That antihypertensive drug selection guided by activity of the renin angiotensin system will be superior to the strategy advocated in JNC 7 in achieving blood pressure control on monotherapy.

Background: the National Heart, Lung, and Blood Institute, through the Joint National Committee on the Detection, Treatment and Control of Hypertension (JNC 7) has recommended that most hypertensive patients begin therapy with a diuretic and sequentially add other classes of drugs until blood pressure is controlled. This approach appears to assume homogeneity in the mechanism by which BP is controlled in different patients. When this standardized strategy has been rigidly applied in Clinical Trials, a majority of patients generally require 2 or more agents to achieve blood pressure control.

The pioneering work of Laragh, Sealey and their colleagues, widely confirmed by others, suggests instead that heterogeneity, in fact, characterizes patterns of blood pressure control in populations. This heterogeneity can be exposed through assessment of the activity of the renin angiotensin system (RAS). Specifically, volume and vasoconstriction determine blood pressure control. Patients in whom volume predominates have suppressed RAS, and, conversely, those in whom vasoconstriction predominates will have an activated RAS. This can be simply and accurately determined by estimation of plasma renin activity (PRA).

It has been demonstrated that volume and vasoconstriction dependent hypertensive patients respond best to different drugs. By exploitation of the RAS it is possible to provide rational therapy to each patients according to the mechanism by which blood pressure is controlled. The result is that appropriate therapy can be both more effective and more efficient. A specific system the Laragh Method has been designed to translate this physiologically based paradigm into a practical scheme or patient management.

The purpose of this trial is to determine whether the Laragh Method will lead to better and more efficient blood pressure control in a general population of hypertensive patients than does the existing treatment strategy. The measure by which this hypothesis will be tested is percentage of hypertensive patients achieving blood pressure control on monotherapy.

The significance of this trial is enormous for both individuals and society. Some 50 million Americans have hypertension and more than 25 million are currently in treatment. If the Laragh Method leads to more parsimonious and effective care, it will mean literally millions of individual patients will be spared the burden of unnecessary polypharmacy. Moreover, the strain on health care costs associated with antihypertensive therapy will be redu

Eligibility


Ages Eligible for Study:	40 Years to 85 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males and females, 40 to 85 years of age
Sustained systolic blood pressure between 140-180 mm Hg
Free of antihypertensive therapy at randomization for at least 4 weeks

Exclusion criteria:

Ages <40, or >85 years
Systolic blood pressure >180 mm Hg
Blood pressure >180/105 mm Hg during the washout period
Require antihypertensive agents for non-blood pressure indications
Taking clonidine
On a beta-blocker drug and have known or suspected coronary artery disease
Documented history of a heart attack, new onset of chest pain, or a coronary revascularization procedure within the past year, congestive heart failure
Serious intercurrent illness
An active ulcer
Have certain abnormal laboratory tests (elevated serum creatinine >1.5 mg/dl, transaminase > 2 times upper limit of normal or active liver disease),
Hypersensitivity, allergy or have an intolerance to angiotensin II receptor blockers (olmesartan), hydrochlorothiazide or amlodipine
Mentally or legally unable to participate
Have or are currently abusing alcohol, have abused drugs within the past 2 years
Have been in another drug study in the past month.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00834600

Locations


United States, New York
Lincoln Medical and Mental Health Center
Bronx, New York, United States, 10451
Albert Einstein College of Medicine - GCRC
Bronx, New York, United States, 10461
Jacobi Medical Center
Bronx, New York, United States, 10461
Bronx Nephrology Hypertension, PC
Bronx, New York, United States, 10467
Ralph Yung, MD
Bronx, New York, United States, 10467

Sponsors and Collaborators

The Louis & Rachel Rudin Foundation

Daiichi Sankyo Inc.

Investigators


Principal Investigator:	Michael H Alderman, M.D.	Albert Einstein College of Medicine of Yeshiva University

More Information

Publications:

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003 Dec;42(6):1206-52. Epub 2003 Dec 1.

Laragh JH: Laragh's Lessons in Renin System Pathophysiology for Treating Hypertension and its Fatal Cardiovascular Consequences. Elsevier Science Inc.,2002,N.Y.

Laragh JH, Sealey JE. Renin system understanding for analysis and treatment of hypertensive patients: a means to quantify the vasoconstrictor elements, diagnose curable renal and adrenal causes, assess risk of cardiovascular morbidity, and find the best-fit drug regimen. Chapter 107, In: Hypertension:Pathophysiology Diagnosis and Management, 2nd Edition, Edited by JH Laragh and BM Brunner. Raven Press,Ltd.,New York 1995.

Sealey JE. Measurement of the hormones of the renin system in hypertensive patients. Clin Biochem. 1981 Oct;14(5):273-81. Review.


Responsible Party:	Michael H. Alderman, Professor of Epidemiology and Population Health, The Louis & Rachel Rudin Foundation
ClinicalTrials.gov Identifier:	NCT00834600 History of Changes
Other Study ID Numbers:	04-074 MMC #05-02-054
Study First Received:	January 30, 2009
Last Updated:	April 18, 2012
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:


Olmesartan Olmesartan Medoxomil Amlodipine Hydrochlorothiazide Antihypertensive Agents Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists Molecular Mechanisms of Pharmacological Action	Calcium Channel Blockers Membrane Transport Modulators Vasodilator Agents Diuretics Natriuretic Agents Physiological Effects of Drugs Sodium Chloride Symporter Inhibitors

ClinicalTrials.gov processed this record on September 26, 2016