Safety Study of Chimeric Natriuretic Peptide(CD-NP) in Stable LVAD Patients

NCT ID: NCT01750905

Last Updated: 2016-08-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2016-08-31

Brief Summary

The most promising chimeric natriuretic peptide designed and studied by our group has been CD-NP which has anti-fibrotic and cardioprotective properties in vivo, vitro and in normal volunteers and human heart failure patients. Since left ventricular assist device (LVAD) can not reverse remodeling of the heart whereas it can improve hemodynamics, CD-NP may be novel anti-fibrotic and anti-remodeling drug as co-therapy during LVAD support.

Detailed Description

This study is a double blind, placebo-controlled phase I trial of the safety and neurohumoral activity of CD-NP, in the treatment of heart failure with LVAD support. Subjects more than 3 months after LVAD implantation will be screened at outpatient clinic visit appointments lists and interested qualified subjects will be either confronted at a visit or sent a letter in the mail to be consented and offered participation in this trial. Once consent has been obtained, baseline values will be established at day 1 and subjects will be given subcutaneous injection of placebo or CD-NP and stay overnight on two different visits in the Clinical Research Unit (CRU). Participant's will receive both placebo and the CD-NP during the study, one per visit. A final follow-up visit for clinical assessment will be conducted over the phone at the end of the study.

Potential subjects who present to Mayo Clinic, Rochester, Minnesota for follow up clinical visit after LVAD implantation will be identified by the study coordinator. A $300 remuneration per subject will be involved to compensate for the inconvenience to the subject. A $500 reimbursement of gas mileage will be provided for those who travel.

Conditions

Left Ventricular Insufficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: TRIPLE

Study Groups

CD-NP

CD-NP 5 ug/kg subcutaneous injection (SQ)

Group Type: ACTIVE_COMPARATOR

CD-NP

Intervention Type: DRUG

CD-NP 5 ug/kg subcutaneous injection (SQ)

Placebo

Placebo: Vehicle (D5W) SQ

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Vehicle (D5W) SQ

Interventions

CD-NP

CD-NP 5 ug/kg subcutaneous injection (SQ)

Intervention Type: DRUG

Placebo

Vehicle (D5W) SQ

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and non-pregnant/post-menopausal female, ages 18-90, in end-stage Heart Failure (HF) with LVAD support who are stable in the healed stage after at least 3 months from the LVAD implant (Destination therapy only) (the post-menopausal state is defined as the absence of menses for ≥ 1 year and serum follicle-stimulating hormone ≥ 20 IU/L; sterilization in the female is defined as bilateral tubal occlusion for ≥ 6 months, bilateral oophorectomy, or complete hysterectomy)
• Be willing to provide informed consent.

Exclusion Criteria

• Known allergy or other adverse reactions to exogenous natriuretic peptides (CD-NP or its components, nesiritide, other natriuretic peptides, or related compounds).
• Women who are pregnant, or breast-feeding.
• Having received nesiritide within 7 days prior to prior to entry into the study.
• Having received any investigational drug or device within 30 days prior to entry into the study.
• Clinically unstable patients (e.g. mean blood pressure < 70 mmHg, ongoing requirement for vasopressors, or mechanical ventilation).
• Recent hospitalization for decompensated HF or recent defibrillation for cardiac resuscitation within 30 days prior to randomization.
• Patients with guarded prognosis who are unlikely to derive meaningful benefit from CD-NP.
• Use of sulfonamides, non-steroidal anti-inflammatory drugs, probenecid, or other drugs that are known to alter renal function within one week of the first dose of CD-NP or placebo.
• Presence of cardiac lesions or comorbidities that may contraindicate the use of natriuretic peptides, such as clinically significant cardiac valvular stenosis, hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or uncorrected congenital heart disease that contraindicates the use of vasodilators.
• Symptomatic carotid artery disease, known critical carotid stenosis, or stroke within the past 3 months
• Clinically significant renal artery stenosis
• Baseline hemoglobin < 9.0 g/dl.
• Serum sodium < 130 mEq/L, potassium < 3.6 milliequivalents per Liter (mEq/L), or magnesium < 1.5 mEq/L.
• Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at least 5 times the upper limit of normal or bilirubin at least 5 times the upper limit of normal
• Creatinine clearance (CrCl) < 30 ml.min-1.1.73m-2, as calculated by Cockcroft-Gault formula(35) and adjusted for body surface area within 3 months or at screening, or requirement for dialysis.
• History of alcohol or drug abuse within the past 6 months.
• Inability to communicate effectively with study personnel.
• BMI >40

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

John A. Schirger

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John Schirger, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

12-001869

Identifier Type: -

Identifier Source: org_study_id