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

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.

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