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

This study has been completed.
Sponsor:
Collaborator:
Thoratec Corporation
Information provided by (Responsible Party):
Nicholas Haglund, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01571037
First received: May 6, 2011
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Inhaled Milrinone Use in Patients Receiving HeartMate II LVAD: A Pilot Study

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Safety [ Time Frame: 12 and 24 hours ] [ Designated as safety issue: Yes ]
    1. Arrhythmias:

      • Atrial
      • Ventricular
    2. 'Sustained' hypotension
    3. Hypersensitivity reaction to milrinone


Secondary Outcome Measures:
  • Efficacy - Hemodynamic [ Time Frame: 30, 60 minutes, then every 4 hours thereafter ] [ Designated as safety issue: No ]

    Invasive Hemodynamic pulmonary catheter:

    • PAS, PAD, mPAP, RA pressures, PCWP, CI, RVSWi (calculated), TPG, PVR, and SvO2

  • Efficacy - Echocardiographic [ Time Frame: Pre op Echocardiography, intraoperative TEE (before and after inhaled milrinone) and postoperative Echocardiography within 48 hours of milrinone initiation ] [ Designated as safety issue: No ]

    Echocardiographic

    • RV dimensions
    • RV systolic functional assessment
    • Tricuspid valve regurgitation
    • Pulmonary Vascular resistance


Enrollment: 10
Study Start Date: April 2012
Study Completion Date: February 2014
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01571037

Locations
United States, Nebraska
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
  More Information

No publications provided

Responsible Party: Nicholas Haglund, MD, Chief Cardiology Fellow, University of Nebraska
ClinicalTrials.gov Identifier: NCT01571037     History of Changes
Other Study ID Numbers: 195-11-FB
Study First Received: May 6, 2011
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Nebraska:
mechanical circulatory assist device

Additional relevant MeSH terms:
Heart Diseases
Ventricular Dysfunction
Ventricular Dysfunction, Right
Cardiovascular Diseases
Milrinone
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Vasodilator Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014