Inhaled Milrinone Use in Patients Receiving HeartMate II LVAD: A Pilot Study

NCT01571037 | Completed Phase 1 DMC

• 1 other identifier: 0195-11-FB
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Right ventricular (RV) failure occurs in an estimated 5-41% of cases involving left ventricular assist device (LVAD) implantation and has been shown to adversely affect peri-operative morbidity and mortality. Current therapies to improve RV dysfunction pre and post-operatively are limited. Inhaled milrinone has been shown in several small human studies to be safely tolerated and provide favorable effects on pulmonary hemodynamics. Study Hypothesis: Delivery of inhaled milrinone, a phosphodiesterase III inhibitor, may provide pulmonary artery vasodilation and therefore improved RV function in patients with end stage heart failure receiving HeartMate II LVAD as a bridge to cardiac transplantation or as destination therapy. Specifically, we aim to:

• demonstrate safety of inhaled milrinone in this patient cohort
• demonstrate efficacy of inhaled milrinone in this patient cohort

Conditions

End Stage Heart Disease; Right Ventricular Dysfunction

Keywords

mechanical circulatory assist device

Outcome Measures

Primary Outcomes (1)

• Safety: Incidence of Arrhythmias, Hypotension and Hypersensitivity Reaction

  1. Arrhythmias: * Atrial * Ventricular 2. 'Sustained' hypotension 3. Hypersensitivity reaction to milrinone

  12 and 24 hours

Secondary Outcomes (2)

• Efficacy - Hemodynamic

  30, 60 minutes, then every 4 hours thereafter

• Efficacy - Echocardiographic

  Pre-op Echocardiography, intraoperative TEE (before and after inhaled milrinone) and postoperative Echocardiography within 48 hours of milrinone initiation

Study Arms (1)

inhaled nebulized Milrinone

OTHER

Drug: Inhaled, nebulized, Milrinone 1 mg/ml milrinone (dissolved in dextrose) and diluted in 0.9% normal saline in a 1:1 ratio to final drug concentration of 0.5mg/ml will be delivered via an IV pump at a fixed dose of 12 ml/hour which will run into a vibrating mesh nebulizer reservoir, connected to the mechanical ventilator circuit. Inhaled milrinone will begin at time of resumption of mechanical ventilation when initiating wean from cardiopulmonary bypass after LVAD implantation in the operating room, and run continuously for a total maximum duration of 24 hours OR until the patient is extubated whichever occurs first. Plasma milrinone levels will be assessed to determine if systemic milrinone absorption occurs after prolonged milrinone inhalation.

Drug: Inhaled, nebulized, Milrinone; Drug: inhaled nebulized milrinone

Interventions

inhaled nebulized milrinone DRUG

0.5 mg/ml inhaled nebulized milrinone deliver at 12 ml/hr continuously until either 24 hours or extubated.

Also known as: Primacor

inhaled nebulized Milrinone

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For BTT candidates:
• Must be an approved candidate for heart transplantation according to institutional policy
• For DT candidates:
• Patients with New York Heart Association (NYHA) class IV symptoms that have failed to respond to maximal medical therapy including beta blocker and angiotensin converting enzyme inhibitors if tolerated for at least 45 of 60 days, OR dependence on continuous inotropic therapy for 14 days OR dependence on intra-aortic balloon pump (IABP) for 7 days
• Left ventricular ejection fraction (LVEF) \< 25%
• Patients with functional limitations on cardiopulmonary stress testing with a peak oxygen consumption of ≤ 14 ml/kg/min unless balloon pump or inotrope dependent or physically unable to perform the test.
• Patients not deemed to be a heart transplant candidate after evaluation
• Must have mean PAP \> 25 mmHg by pulmonary catheter indices pre-operatively (within 72 hrs) and/or a PVR \> 3 Woods units (WU).
• Age ≥ 19 years old (in the state of Nebraska, an individual must be ≥ 19 years old to legally provide consent as compared to age ≥ 18 in most other states)
• Signed informed consent

You may not qualify if:

• Age \< 19 years old
• Pregnancy or current breast feeding
• Undergoing cardiac transplantation without implantation of mechanical assist device
• Documented medical allergy to milrinone

Sponsors & Collaborators

• University of Nebraska: lead
• Thoratec Corporation: collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198-2265, United States

Location

MeSH Terms

Conditions

Ventricular Dysfunction, Right

Interventions

Inhalation; Milrinone

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Amrinone; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nicholas A Haglund, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2011
• First Posted: April 4, 2012
• Study Start: April 5, 2012
• Primary Completion: February 1, 2013
• Study Completion: February 21, 2014
• Last Updated: September 6, 2023

Record last verified: 2023-08

Locations

US (1)