Renin Profiling in Selection of Initial Antihypertensive Drug

This study has been completed.
Sponsor:
Collaborator:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Michael H. Alderman, The Louis & Rachel Rudin Foundation
ClinicalTrials.gov Identifier:
NCT00834600
First received: January 30, 2009
Last updated: April 18, 2012
Last verified: October 2010
  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:


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

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

Locations
United States, New York
Albert Einstein College of Medicine - GCRC
Bronx, New York, United States, 10461
Ralph Yung, MD
Bronx, New York, United States, 10467
Jacobi Medical Center
Bronx, New York, United States, 10461
Lincoln Medical and Mental Health Center
Bronx, New York, United States, 10451
Bronx Nephrology Hypertension, PC
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:
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:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Olmesartan medoxomil
Antihypertensive Agents
Hydrochlorothiazide
Amlodipine
Olmesartan
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium Channel Blockers
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on April 16, 2014