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

NCT ID: NCT00405639

Last Updated: 2014-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2013-05-31

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.

Detailed Description

Participants in this study will be randomized to receive BNP or placebo (an inactive, saline shot). The participant will need to give themselves a shot in their stomach (similar to diabetics giving themselves insulin) twice a day for twelve weeks. The study requires a screening visit to determine eligibility and discuss the study. At this visit a blood draw for heart and liver function and a six minute walk will be done. There will also be two other outpatient visits and two inpatient stays, for 48 hours, in the General Clinical Research Center (GCRC) at St. Marys Hospital. During the two in-patient stays in the GCRC, blood and urine samples will be done to get heart and kidney function as well as a research echo. After enrollment, the study lasts for twelve weeks. There is a one week visit in outpatient setting getting a blood draw and a 6 week visit in outpatient setting to get a blood draw, 24 hour urine collection and resupply the study medication. There is a one week visit in outpatient setting getting a blood draw and a 6 week visit in outpatient setting to get a blood draw, 24 hour urine collection and resupply the study medication.

Conditions

Heart Failure; Asymptomatic Systolic Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Nesiritide

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.

Group Type: ACTIVE_COMPARATOR

Nesiritide

Intervention Type: 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.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Normal saline will be used for placebo.

Interventions

Nesiritide

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.

Intervention Type: DRUG

Placebo

Normal saline will be used for placebo.

Intervention Type: DRUG

Other Intervention Names

Natrecor; Human B-type natriuretic peptide (BNP)

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Horng Chen

Dr Horng H. Chen

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Horng H. Chen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

P01HL076611

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UL1RR024150

Identifier Type: NIH

Identifier Source: secondary_id

View Link

05-004186

Identifier Type: -

Identifier Source: org_study_id