Nesiritide in Resistant Hypertension

NCT ID: NCT01514357

Last Updated: 2018-03-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2014-07-31

Brief Summary

Hypothesis: If the use of B-type natriuretic peptide (BNP) is proven to be effective in controlling high blood pressure, it may lead to a reduction of standard therapy and improved cardiovascular and kidney protection.

Detailed Description

Hypertension remains a global burden in cardiovascular disease leading to stroke, myocardial infarction, and heart failure. Its myocardial complications result from increased mechanical load on the heart. Under physiological conditions of increased myocardial load and resulting myocardial stretch, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) synthesis and secretion occur contributing to maintenance of optimal cardiorenal and blood pressure homeostasis. However, studies indicate that in subjects with cardiovascular diseases the biological structure of these hormones may be altered, thus reducing their favorable protective activities. New studies indicate that early and moderate hypertension is associated with a derangement of the natriuretic peptide system which is characterized by the lack of activation of biologically active ANP and BNP, while severe hypertension is characterized by cardiac release of altered molecular forms of ANP and BNP that have reduced biological properties and/or enhanced degradation.

The broad objective of proposal is to advance the biology and therapeutics of the natriuretic peptides (NPs) with a special focus on the cardiac peptide BNP in human hypertension. The investigators' proposal is based upon the biological properties of BNP (i.e., natriuretic, renin-angiotensin-aldosterone suppressing, vasodilating, anti-fibrotic, anti-hypertrophic and positive lusitropic), its mechanistic role in human hypertension, and thus its potential as an innovative chronic protein therapeutic to enhance the treatment of patients with uncontrolled and or resistant hypertension. Importantly, BNP is an endocrine hormone normally produced by the human heart, and its use as therapeutic agent has been approved in USA for more than a decade and has been proven to be safe.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Nesiritide (BNP)

Subjects will receive subcutaneous (SQ) BNP bid for seven consecutive days. The initial starting dose was 5 micrograms/kg.

Group Type: OTHER

Nesiritide (BNP)

Intervention Type: DRUG

NATRECOR® (nesiritide) is a sterile, purified preparation of human B-type natriuretic peptide (hBNP), and is manufactured from E. coli using recombinant DNA technology. Each 1.5 mg vial contains a white- to off-white lyophilized powder for intravenous (IV) administration after reconstitution.

Placebo

Subjects will receive SQ placebo bid for seven consecutive days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered subcutaneously instead of active drug (nesiritide) in a blind fashion in the second arm of the study.

Interventions

Nesiritide (BNP)

NATRECOR® (nesiritide) is a sterile, purified preparation of human B-type natriuretic peptide (hBNP), and is manufactured from E. coli using recombinant DNA technology. Each 1.5 mg vial contains a white- to off-white lyophilized powder for intravenous (IV) administration after reconstitution.

Intervention Type: DRUG

Placebo

Placebo will be administered subcutaneously instead of active drug (nesiritide) in a blind fashion in the second arm of the study.

Intervention Type: DRUG

Other Intervention Names

Natrecor; saline solution

Eligibility Criteria

Inclusion Criteria

Subjects with resistant hypertension as defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines, systolic blood pressure and/or diastolic blood pressure > 140/90 mm Hg. For patients with hypertension and diabetes or renal disease, blood pressure > 130/80 mm Hg despite treatment with diuretic, sympathetic depressant and vasodilators.

Medications may include a three drug regimen including:

• diuretic at therapeutic dose
• a second line agent such as sympatholytic (e.g. beta-blockade, central agent such as clonidine) or angiotensin converting enzyme inhibitor (ACEi) / angiotensin receptor blocker (ARB) or calcium channel blocker (CCB).
• third line agent including one of the above and/or direct vasodilator, such as hydralazine or minoxidil.

Exclusion Criteria

• Congestive Heart Failure (any New York Heart Association (NYHA) class)
• Ejection Fraction < 50%
• Known renal artery stenosis
• Myocardial infarction within 3 months of screening
• Unstable angina within 14 days of screening, or any evidence of myocardial ischemia
• Moderate to severe pulmonary hypertension
• Valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
• Sustained Atrial Fibrillation
• Second or third degree atrioventricular (AV) block without a permanent cardiac pacemaker
• Cerebral vascular accident within 3 months of screening, or other evidence of significantly compromised central nervous system perfusion
• Total bilirubin of > 1.5 mg/dL or aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 1.5 times the upper limit of normal range
• Renal insufficiency assessed by calculated Glomerular Filtration Rate (GFR) < 30 ml/min (Cockcroft-Gault equation)
• Serum sodium of < 125 milliequivalent (mEq)/dL or > 160 mEq/dL
• Serum potassium of < 3.0 mEq/dL or > 5.5 mEq/dL
• Women taking hormonal contraceptives
• Pregnancy
• Body mass index (BMI) > 35

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

John C Burnett

OTHER

Sponsor Role: lead

Responsible Party

John C Burnett

Professor of Medicine and Physiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John C Burnett, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

UL1RR024150

Identifier Type: NIH

Identifier Source: secondary_id

View Link

11-001372

Identifier Type: -

Identifier Source: org_study_id