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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01750905
Recruitment Status : Completed
First Posted : December 17, 2012
Last Update Posted : August 30, 2016
Information provided by (Responsible Party):
John A. Schirger, Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Left Ventricular Insufficiency Drug: CD-NP Drug: Placebo Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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
Study Start Date : April 2013
Actual Primary Completion Date : May 2016
Actual Study Completion Date : August 2016

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Number of subjects with Hypotension [ Time Frame: approx day 9 ]

Secondary Outcome Measures :
  1. Mean plasma Cyclic guanosine monophosphate (cGMP) level [ Time Frame: Approx day 9 ]
  2. Mean aldosterone level [ Time Frame: approx 9 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01750905

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

Responsible Party: John A. Schirger, MD, Mayo Clinic Identifier: NCT01750905     History of Changes
Other Study ID Numbers: 12-001869
First Posted: December 17, 2012    Key Record Dates
Last Update Posted: August 30, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases