Clinical trial NCT01571037: Inhaled Milrinone Use in Patients Receiving HeartMate II LVAD: A Pilot Study
Official title: Inhaled Milrinone Use in Patients Receiving HeartMate II LVAD: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: End Stage Heart Disease
Right Ventricular Dysfunction
Keywords: mechanical circulatory assist device
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: Thoratec Corporation
First posted: 2012-04-04
Enrollment: 10
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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, the aims are:

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

Eligibility criteria: Inclusion Criteria:

1. For BTT candidates:

   * Must be an approved candidate for heart transplantation according to institutional policy
2. 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

Exclusion Criteria:

* Age \< 19 years old
* Pregnancy or current breast feeding
* Undergoing cardiac transplantation without implantation of mechanical assist device
* Documented medical allergy to milrinone
* Failure to meet inclusion criteria for LVAD implantation for BTT or DT indications

Primary outcomes:
measure: Safety: Incidence of Arrhythmias, Hypotension and Hypersensitivity Reaction
timeFrame: 12 and 24 hours
Secondary outcomes:
measure: Efficacy - Hemodynamic
timeFrame: 30, 60 minutes, then every 4 hours thereafter
measure: Efficacy - Echocardiographic
timeFrame: Pre-op Echocardiography, intraoperative TEE (before and after inhaled milrinone) and postoperative Echocardiography within 48 hours of milrinone initiation
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Nicholas A Haglund, MD
role: PRINCIPAL_INVESTIGATOR
References: