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Nesiritide in Resistant Hypertension

This study has been terminated.
(Original PI left the institution, and lack of funding.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01514357
First Posted: January 23, 2012
Last Update Posted: October 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
John C Burnett, Mayo Clinic
  Purpose
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.

Condition Intervention Phase
Hypertension Drug: Nesiritide (BNP) Drug: Placebo Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Novel Peptides in Resistant Human Hypertension

Resource links provided by NLM:


Further study details as provided by John C Burnett, Mayo Clinic:

Primary Outcome Measures:
  • 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.


Enrollment: 12
Actual Study Start Date: April 2012
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Nesiritide (BNP)
Subjects will receive subcutaneous (SQ) BNP bid for seven consecutive days. The initial starting dose was 5 micrograms/kg.
Drug: 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.
Other Name: Natrecor
Placebo Comparator: Placebo
Subjects will receive SQ placebo bid for seven consecutive days.
Drug: Placebo
Placebo will be administered subcutaneously instead of active drug (nesiritide) in a blind fashion in the second arm of the study.
Other Name: saline solution

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

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): NCT01514357


Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
John C Burnett
National Center for Research Resources (NCRR)
Investigators
Principal Investigator: John C Burnett, M.D. Mayo Clinic
  More Information

Responsible Party: John C Burnett, Professor of Medicine and Physiology, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01514357     History of Changes
Other Study ID Numbers: 11-001372
UL1RR024150 ( U.S. NIH Grant/Contract )
First Submitted: January 12, 2012
First Posted: January 23, 2012
Results First Submitted: April 27, 2017
Results First Posted: October 20, 2017
Last Update Posted: October 20, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs