Human B-type Natriuretic Peptide (BNP) (Nesiritide) to Help Heart, Kidney, and Hormonal Functions in Persons With Lower Heart Pumping Function

NCT00405639 | Completed Phase 1 Results DMC

• 3 other identifiers: 05-004186P01HL076611UL1RR024150
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The following are done for screening procedures to determine if patients are eligible for this study: blood count, kidney and liver blood tests. Patients will complete a 6-minute walk test. Patients will be instructed to follow a no-added-salt diet for 1-3 weeks before the study and for the whole duration of the study. Diet instructions will be given to the patient and the patient will collect his/her urine for 24 hours before the active study day. Patients will need to avoid strenuous exercise and abstain from smoking, alcohol, and caffeine for 3 days prior to the study days. Patients will remain on their regular medications.

Conditions

Heart Failure; Asymptomatic Systolic Dysfunction

Outcome Measures

Primary Outcomes (1)

• Change in Urinary Sodium Excretion in Response to Saline Load

  baseline, 12 weeks

Secondary Outcomes (3)

• Change in Urine Flow in Response to Saline Load

  baseline, 12 weeks

• Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) in Response to Saline Load

  baseline, 12 weeks

• Change in Left Ventricular Mass Index

  baseline, 12 weeks

Study Arms (2)

Nesiritide

ACTIVE COMPARATOR

Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.

Drug: Nesiritide

Placebo

PLACEBO COMPARATOR

Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.

Drug: Placebo

Interventions

Nesiritide DRUG

Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.

Also known as: Natrecor, Human B-type natriuretic peptide (BNP)

Nesiritide

Placebo DRUG

Normal saline will be used for placebo.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with an ejection fraction of less than 45%
• No clinical signs or symptoms of congestive heart failure
• Ability to walk a minimal distance of \> 450 meters on a 6-minute walk. If the subject is not able to walk 450 meters due to pain in hips and knees and not fatigue or shortness of breath, they will still qualify for the protocol.
• The subjects will all be on stable doses of an angiotensin converting enzyme (ACE) inhibitor for two weeks prior to the active study date.
• Therapy with other vasodilators, beta-receptor antagonists, digoxin and antiarrhythmic medications will be allowed, however, all medications must be at stable doses two weeks prior to the study date.

You may not qualify if:

• Myocardial infarction within 3 months of screening
• Unstable angina within 14 days of screening, or any evidence of myocardial ischemia
• Significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
• Severe congenital heart diseases
• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
• Second or third degree heart block without a permanent cardiac pacemaker
• Stroke within 3 months of screening, or other evidence of significantly compromised central nervous system (CNS) perfusion
• Total bilirubin of \> 1.5 mg/dL or other liver enzymes \>1.5 times the upper limit of normal
• Serum creatinine of \> 3.0 mg/dL
• Serum sodium of \< 125 milliequivalent (mEq)/dL or \> 160 mEq/dL
• Serum potassium of \< 3.5 mEq/dL or \> 5.0 mEq/dL change to 5.3
• Serum digoxin level of \> 2.0 ng/ml
• Systolic pressure of \< 85 mmHg
• Hemoglobin \< 10 gm/dl

Sponsors & Collaborators

• Mayo Clinic: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Natriuretic Peptide, Brain

Condition Hierarchy (Ancestors)

Heart 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

Results Point of Contact

• Title: Dr. Horng H. Chen
• Organization: Mayo Clinic

chen.horng@mayo.edu

507-538-2354

Study Officials

• Horng H. Chen, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Horng H. Chen

Study Record Dates

• First Submitted: November 29, 2006
• First Posted: November 30, 2006
• Study Start: June 1, 2006
• Primary Completion: April 1, 2011
• Study Completion: May 1, 2013
• Last Updated: March 17, 2014
• Results First Posted: March 17, 2014

Record last verified: 2014-02

Locations

US (1)