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

Sponsor

University of Nebraska (Other)

Overall Status

Completed

CT.gov ID

NCT01571037

Collaborator

Thoratec Corporation (Industry)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
End Stage Heart Disease Right Ventricular Dysfunction	Drug: Inhaled, nebulized, Milrinone Drug: inhaled nebulized milrinone	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: inhaled nebulized Milrinone 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 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 0.5 mg/ml inhaled nebulized milrinone deliver at 12 ml/hr continuously until either 24 hours or extubated.

Arm

Intervention/Treatment

Other: inhaled nebulized Milrinone

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

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

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

Outcome Measures

Primary Outcome Measures

Safety [12 and 24 hours]
Arrhythmias: Atrial Ventricular 'Sustained' hypotension Hypersensitivity reaction to milrinone

Secondary Outcome Measures

Efficacy - Hemodynamic [30, 60 minutes, then every 4 hours thereafter]
Invasive Hemodynamic pulmonary catheter: PAS, PAD, mPAP, RA pressures, PCWP, CI, RVSWi (calculated), TPG, PVR, and SvO2
Efficacy - Echocardiographic [Pre op Echocardiography, intraoperative TEE (before and after inhaled milrinone) and postoperative Echocardiography within 48 hours of milrinone initiation]
Echocardiographic RV dimensions RV systolic functional assessment Tricuspid valve regurgitation Pulmonary Vascular resistance

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-2265

Sponsors and Collaborators

University of Nebraska
Thoratec Corporation

Investigators

Principal Investigator: Nicholas A Haglund, MD, University of Nebraska

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Nicholas Haglund, MD, Chief Cardiology Fellow, University of Nebraska

ClinicalTrials.gov Identifier:

NCT01571037

Other Study ID Numbers:

195-11-FB

First Posted:

Apr 4, 2012

Last Update Posted:

Mar 4, 2014

Last Verified:

Feb 1, 2014

Keywords provided by Nicholas Haglund, MD, Chief Cardiology Fellow, University of Nebraska

mechanical circulatory assist device

Additional relevant MeSH terms:

Heart Diseases

Ventricular Dysfunction

Ventricular Dysfunction, Right

Milrinone

Study Results

No Results Posted as of Mar 4, 2014