Nesiritide in Resistant Hypertension
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Natriuretic Peptides and Their Chimerics in Hypertension (Aims 1 and 2)|
- Changes in blood pressure (BP) with treatment over 7 days [ Time Frame: baseline and at 7 days ] [ Designated as safety issue: No ]The primary endpoint of the study is the change in BP with treatment over 7 days. This will be assessed by the 24-hour ambulatory blood pressure monitoring (ABPM) recordings performed at baseline (day 0) and at day 6 (post-treatment). Group comparisons will be based on the overall (24-hour) mean, the daytime mean, and the night-time mean.
- Renal function [ Time Frame: Baseline and after 7 days treatment ] [ Designated as safety issue: No ]The secondary endpoints will include renal function as assessed by calculated glomerular filtration rate (GFR) and cystatin-C, effects of SQ BNP on 24-hour sodium excretion.
- Hormonal changes [ Time Frame: Baseline and after 7 days treatment ] [ Designated as safety issue: No ]The effects upon the endogenous NPs system determined by changes in ANP, NT-ANP, proBNP1-108, NT-proBNP, cyclic guanylate monophosphate (cGMP), and suppression of the renin-angiotensin-aldosterone system (RAAS) will also be assessed.
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||November 2016|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
Nesiritide (BNP) doses
Patients will receive low, medium and high dose of subcutaneous (SQ) BNP to determine the feasibility, safety, and blood pressure lowering effect of BNP so as to identify the optimal dose.
Drug: Nesiritide (BNP)
This arm is designed to determine the optimal dose rage of nesiritide (BNP) to be used in the double blind trial (second arm of the study).
Other Name: Natrecor
Active Comparator: SQ Nesiritide (BNP)
Patients will receive SQ BNP bid at the optimal dose, as assessed in the dose finding arm, for seven consecutive days.
Drug: Nesiritide (BNP)
The optimal dose rage of nesiritide (BNP) to be used in the double blind trial will be determined in the first dose finding arm.
Other Name: Natrecor
Placebo Comparator: Placebo
Patients 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 Name: saline solution
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. Our 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01514357
|United States, Minnesota|
|Mayo Clinic in Rochester|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Alessandro Cataliotti, MD, PhD||Mayo Clinic|