Nesiritide in Hypertension

NCT02608996 | Recruiting Phase 1 DMC

• 1 other identifier: 2015-000577-13
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

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 this proposal is to advance the biology and therapeutics of the 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 hypertension. Importantly, BNP is an endocrine hormone normally produced by the human heart, and it has been approved for the treatment of acute heart failure in USA.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Changes in blood pressure (BP)

  Office blood pressure and ambulatory blood pressure monitoring (ABPM) recordings will be used for the analysis

  48 hours, from day 1 to day 2. Specifically, it will be assessed before first injection(baseline data) up to 12 hours post last injection.

Secondary Outcomes (3)

• Renal function as assessed by estimated glomerular filtration rate (eGFR)

  48 hours, from day 1 to day 2. Specifically, it will be assessed before first injection (baseline data) up to 12 hours post last injection.

• Hormonal changes assessed by aldosterone, atrial natriuretic peptide (ANP), N Terminal-ANP, BNP, N Terminal-proBNP, C-type natriuretic peptide and cyclic guanosyl monophosphate.

  48 hours, from day 1 to day 2. Specifically, it will be assessed before first injection (baseline data) up to 12 hours post last injection.

• Number of participants with treatment-related adverse events defined as all untoward and unintended responses to the treatment related to any dose administered.

  48 hours, from day 1 to day 2. Specifically, it will be assessed after first injection, up to 12 hours post last injection. A second determination will be done within 3 weeks after last injection (21 days assessment).

Study Arms (2)

Subcutaneous BNP

ACTIVE COMPARATOR

Patients will receive gradually increasing doses (10-25 µg/kg) of subcutaneously administered nesiritide (BNP) twice daily for two days, to determine the feasibility, safety and blood pressure lowering effect of BNP so as to identify the optimal dose.

Drug: Nesiritide

Subcutaneous placebo

PLACEBO COMPARATOR

Patients will receive subcutaneously administered placebo twice daily for two days for determination of the effect of BNP.

Drug: Placebo

Interventions

Nesiritide DRUG

This intervention is designed to determine the optimal dose range of BNP for treatment of patients with uncontrolled hypertension

Also known as: Natrecor, BNP

Subcutaneous BNP

Placebo DRUG

For comparison to elucidate the true effect of nesiritide

Also known as: Saline solution

Subcutaneous placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Average day-time SBP \> 115 on a 24-h ambulatory BP measurement at screening.

You may not qualify if:

• Congestive Heart Failure (any New York Heart Association class)
• Ejection Fraction ≤ 40 %
• Known, not appropriately treated, secondary hypertension
• Myocardial infarction within 3 months of screening
• Unstable angina within 14 days of screening, or any evidence of myocardial ischemia
• Pulmonary hypertension
• Aortic stenosis with maximum jet velocity \> 2,5 m/s
• Other valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis or biopsy proven active myocarditis
• Sustained Ventricular Tachycardia or Ventricular Fibrillation within 14 days of screening
• Sustained Atrial Fibrillation
• Second or third degree atrioventricular block without a permanent cardiac pacemaker
• Cerebrovascular event within 3 months of screening, or other evidence of significantly compromised cerebral perfusion
• Proteinuria defined as albumin:creatinine ratio \> 100 (equivalent to an excretion of \> 1 g/day)
• Nephrotic syndrome
• Body Mass Index \> 35

Sponsors & Collaborators

• Oslo University Hospital: lead
• University of Oslo: collaborator
• University Hospital, Akershus: collaborator

Study Sites (3)

Oslo University Hopital, Rikshospitalet

Oslo, 0424, Norway

NOT YET RECRUITING

Oslo University Hospital, Ullevål Hospital

Oslo, 0450, Norway

RECRUITING

Akershus University Hospital

Strømmen, 1478, Norway

RECRUITING

MeSH Terms

Conditions

Hypertension

Interventions

Natriuretic Peptide, Brain; Saline Solution

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Natriuretic Peptides; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Alessandro Cataliotti, MD, PhD

  Oslo University Hospital and University of Oslo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandro Cataliotti, MD, PhD

CONTACT

+47 23016807; alessandro.cataliotti@medisin.uio.no

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, dr. med.

Study Record Dates

• First Submitted: November 9, 2015
• First Posted: November 20, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2018
• Study Completion (Estimated): December 1, 2030
• Last Updated: January 3, 2018

Record last verified: 2017-12

Locations

NO (3)