Nesiritide in Resistant Hypertension

March 21, 2018 updated by: John C Burnett

Novel Peptides in Resistant Human Hypertension

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.

Study Overview

Status

Terminated

Conditions

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Nesiritide (BNP)
Subjects will receive subcutaneous (SQ) BNP bid for seven consecutive days. The initial starting dose was 5 micrograms/kg.
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.
Other Names:
  • Natrecor
PLACEBO_COMPARATOR: Placebo
Subjects will receive SQ placebo bid for seven consecutive days.
Placebo will be administered subcutaneously instead of active drug (nesiritide) in a blind fashion in the second arm of the study.
Other Names:
  • saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Systolic Blood Pressure (BP)
Time Frame: baseline, treatment day 1, treatment day 2
The change in BP with treatment over 7 days was assessed by the mean BP on admission, (treatment day 1) mean BP 23 hours after the first injection of BNP, and mean BP 23 hours after the second injection of BNP (treatment day 2). Treatment day 2 was 7 days after admission.
baseline, treatment day 1, treatment day 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: John C Burnett, M.D., Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 1, 2012

Primary Completion (ACTUAL)

July 1, 2014

Study Completion (ACTUAL)

July 1, 2014

Study Registration Dates

First Submitted

January 12, 2012

First Submitted That Met QC Criteria

January 20, 2012

First Posted (ESTIMATE)

January 23, 2012

Study Record Updates

Last Update Posted (ACTUAL)

March 23, 2018

Last Update Submitted That Met QC Criteria

March 21, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Other Study ID Numbers

  • 11-001372
  • UL1RR024150 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hypertension

Clinical Trials on Nesiritide (BNP)

3
Subscribe