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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John A. Schirger, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01750905
First received: December 13, 2012
Last updated: August 29, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Left Ventricular Insufficiency
Drug: CD-NP
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: A Phase I, Randomized, Double-blind, Placebo-controlled, Crossover Study Evaluating The Safety, Hemodynamic And Neurohumoral Effects of a Novel Chimeric Peptide, CD-NP, in Patients With Left Ventricular Assist

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Number of subjects with Hypotension [ Time Frame: approx day 9 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Mean plasma Cyclic guanosine monophosphate (cGMP) level [ Time Frame: Approx day 9 ] [ Designated as safety issue: No ]
  • Mean aldosterone level [ Time Frame: approx 9 days ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: April 2013
Study Completion Date: August 2016
Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CD-NP
CD-NP 5 ug/kg subcutaneous injection (SQ)
Drug: CD-NP
CD-NP 5 ug/kg subcutaneous injection (SQ)
Placebo Comparator: Placebo
Placebo: Vehicle (D5W) SQ
Drug: Placebo
Vehicle (D5W) SQ

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01750905

Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: John Schirger, MD Mayo Clinic
  More Information

Responsible Party: John A. Schirger, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01750905     History of Changes
Other Study ID Numbers: 12-001869 
Study First Received: December 13, 2012
Last Updated: August 29, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 30, 2016