Subcu Administration of CD-NP in Heart Failure Patients With Left Ventricular Assist Device Support

NCT03091998 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: IRB # 16-004850
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The worldwide use of left ventricular assist devices (LVAD), which is mechanical device to improve hemodynamic function, has improved the outcomes of severe heart failure (HF) patients leading to the continued annual increase in the number of LVAD implantations. However LVAD support still results in major complications such as renal failure or gastrointestinal bleeding. The investigators hypothesize that such major complications may be due to endothelial dysfunction induced by the lack of pulsatility, which may be improved by an innovative designer natriuretic peptide, CD-NP. They have demonstrated its favorable actions in animal models as well as humans, and tested its safety in LVAD patients. They hypothesize that CD-NP will have renal and endothelial protective actions through its receptor GC-A and GC-B. Thus, the investigators will test their hypothesis with a highly translational approach to examine CD-NP's role in endothelial and renal protection. The aim is to determine safety and tolerability together with cGMP activating, neurohumoral modulating and renovascular protective properties of chronic subcutaneous delivery of CD-NP compared to placebo in stable LVAD patients for 3 days.

Conditions

Heart Failure; Left Ventricular Assist Device; Natriuretic Peptide

Outcome Measures

Primary Outcomes (1)

• Hypotension

  To assess safety and tolerability (without symptomatic hypotension or mean blood pressure \<70 mmHg) of chronic continuous subcutaneous infusion administration of CD-NP.

  2 weeks

Secondary Outcomes (3)

• Pharmacokinetic Outcome Characterization

  2 weeks

• Renal Function

  2 weeks

• Endothelial function

  2 weeks

Study Arms (2)

Study Drug (CD-NP)

ACTIVE COMPARATOR

Participants will receive a single subcutaneous injection of CD-NP (5 ug/kg) for 3 days running

Drug: CD-NP

Placebo (saline)

PLACEBO COMPARATOR

Participants will receive a single subcutaneous injection (\~1 mL) of normal saline for 3 days running

Other: Placebo

Interventions

CD-NP DRUG

Participants will receive a subcutaneous injection of CD-NP (5 mcg / kg) daily for 3 days

Also known as: Cenderitide

Study Drug (CD-NP)

Placebo OTHER

Participants will receive an \~ 1mL subcutaneous injection of normal saline, in lieu of Study Drug, for 3 days

Also known as: 0.9% normal saline

Placebo (saline)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and non-pregnant/post-menopausal/sterile females, ages 18-90, in end-stage HF with LVAD support who are stable in the healed stage 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 or 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.
• All cardiac medications must be at stable doses 4 weeks prior to enrollment.

You may not qualify if:

• 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 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.
• 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
• Requirement of pressors for maintenance of blood pressure.
• Intra-aortic blood pump use.
• Severe aortic or mitral stenosis or significant LV outflow tract obstruction.
• Clinically significant renal artery stenosis \> 50%
• Baseline hemoglobin \< 9.0 g/dl.
• Serum sodium \< 130 mEq/L, potassium \< 3.6 mEq/L, or magnesium \< 1.5 mEq/L.

Sponsors & Collaborators

• Mayo Clinic: lead

MeSH Terms

Conditions

Heart Failure

Interventions

cenderitide; Saline Solution

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Tomoko Ichiki, M.D.Ph.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The Research Pharmacists will manage the randomization of the study and release information at the conclusion, once all participants have been recruited and completed study measures.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Injection of CD-NP vs Placebo

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 27, 2017
• Study Start: September 30, 2017
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2020
• Last Updated: July 28, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share