Renin Profiling in Selection of Initial Antihypertensive Drug

NCT00834600 | Completed DMC

• 2 other identifiers: 04-074MMC #05-02-054
• Study Type: interventional
• Target: 185
• Locations: 1 country
• Sites: 5

Brief Summary

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).

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Percent of patients with BP <140/90 mmHg and on monotherapy at the 5th visit.

  3-4 months

Secondary Outcomes (2)

• 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.

  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.

  3-4 months

Study Arms (2)

HCTZ , ARB

EXPERIMENTAL

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; Drug: hydrochlorothiazide (HCTZ) or olmesartan

Conventional antihypertensive therapy

ACTIVE COMPARATOR

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; Drug: hydrochlorothiazide (HCTZ) or olmesartan

Interventions

olmesartan, hydrochlorothiazide, amlodipine DRUG

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

Also known as: Renin guided selection of treatment

Conventional antihypertensive therapy; HCTZ , ARB

hydrochlorothiazide (HCTZ) or olmesartan DRUG

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

Also known as: Standard Therapy

Conventional antihypertensive therapy; HCTZ , ARB

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Louis & Rachel Rudin Foundation: lead
• Daiichi Sankyo: collaborator

Study Sites (5)

Lincoln Medical and Mental Health Center

The Bronx, New York, 10451, United States

Location

Albert Einstein College of Medicine - GCRC

The Bronx, New York, 10461, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Bronx Nephrology Hypertension, PC

The Bronx, New York, 10467, United States

Location

Ralph Yung, MD

The Bronx, New York, 10467, United States

Location

Related Publications (4)

• 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. doi: 10.1161/01.HYP.0000107251.49515.c2. Epub 2003 Dec 1.

  PMID: 14656957 BACKGROUND

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

  BACKGROUND

• 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.

  BACKGROUND

• Sealey JE. Measurement of the hormones of the renin system in hypertensive patients. Clin Biochem. 1981 Oct;14(5):273-81. doi: 10.1016/s0009-9120(81)91000-6. No abstract available.

  PMID: 6120769 BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

olmesartan; Hydrochlorothiazide; Amlodipine; Standard of Care

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Michael H Alderman, M.D.

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Epidemiology and Population Health

Study Record Dates

• First Submitted: January 30, 2009
• First Posted: February 3, 2009
• Study Start: December 1, 2005
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: April 19, 2012

Record last verified: 2010-10

Locations

US (5)