Renin Profiling in Selection of Initial Antihypertensive Drug
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| ClinicalTrials.gov Identifier: NCT00834600 |
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Recruitment Status
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Completed
First Posted
: February 3, 2009
Last Update Posted
: April 19, 2012
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hypertension | Drug: olmesartan, hydrochlorothiazide, amlodipine Drug: hydrochlorothiazide (HCTZ) or olmesartan | Not Applicable |
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
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 185 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Clinical Trial of Renin Profiling in Selection of Initial Antihypertensive Drug |
| Study Start Date : | December 2005 |
| Actual Primary Completion Date : | October 2011 |
| Actual Study Completion Date : | October 2011 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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
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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
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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
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- Percent of patients with BP <140/90 mmHg and on monotherapy at the 5th visit. [ Time Frame: 3-4 months ]
- 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 ]
- 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 ]
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| Ages Eligible for Study: | 40 Years to 85 Years (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00834600
| 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 | |
| Principal Investigator: | Michael H Alderman, M.D. | Albert Einstein College of Medicine, Inc. |
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 |
| First Posted: | February 3, 2009 Key Record Dates |
| Last Update Posted: | April 19, 2012 |
| Last Verified: | October 2010 |
Additional relevant MeSH terms:
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Olmesartan Amlodipine Hydrochlorothiazide Antihypertensive Agents Olmesartan Medoxomil Calcium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action |
Vasodilator Agents Diuretics Natriuretic Agents Physiological Effects of Drugs Sodium Chloride Symporter Inhibitors Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists |