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Nesiritide in Resistant Hypertension

Primary Purpose

Hypertension

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nesiritide (BNP)
Placebo
Sponsored by
John C Burnett
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Placebo Comparator

Arm Label

Nesiritide (BNP)

Placebo

Arm Description

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

Subjects will receive SQ placebo bid for seven consecutive days.

Outcomes

Primary Outcome Measures

Changes in Systolic Blood Pressure (BP)
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.

Secondary Outcome Measures

Full Information

First Posted
January 12, 2012
Last Updated
March 21, 2018
Sponsor
John C Burnett
Collaborators
National Center for Research Resources (NCRR)
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1. Study Identification

Unique Protocol Identification Number
NCT01514357
Brief Title
Nesiritide in Resistant Hypertension
Official Title
Novel Peptides in Resistant Human Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Terminated
Why Stopped
Original PI left the institution, and lack of funding.
Study Start Date
April 2012 (Actual)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
John C Burnett
Collaborators
National Center for Research Resources (NCRR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nesiritide (BNP)
Arm Type
Other
Arm Description
Subjects will receive subcutaneous (SQ) BNP bid for seven consecutive days. The initial starting dose was 5 micrograms/kg.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will receive SQ placebo bid for seven consecutive days.
Intervention Type
Drug
Intervention Name(s)
Nesiritide (BNP)
Other Intervention Name(s)
Natrecor
Intervention Description
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
Intervention Name(s)
Placebo
Other Intervention Name(s)
saline solution
Intervention Description
Placebo will be administered subcutaneously instead of active drug (nesiritide) in a blind fashion in the second arm of the study.
Primary Outcome Measure Information:
Title
Changes in Systolic Blood Pressure (BP)
Description
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.
Time Frame
baseline, treatment day 1, treatment day 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John C Burnett, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Nesiritide in Resistant Hypertension

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