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

Primary Purpose

End Stage Heart Disease, Right Ventricular Dysfunction

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Inhaled, nebulized, Milrinone
inhaled nebulized milrinone
Sponsored by
University of Nebraska
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Heart Disease focused on measuring mechanical circulatory assist device

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Nebraska Medical Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

inhaled nebulized Milrinone

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety: Incidence of Arrhythmias, Hypotension and Hypersensitivity Reaction
Arrhythmias: Atrial Ventricular 'Sustained' hypotension Hypersensitivity reaction to milrinone

Secondary Outcome Measures

Efficacy - Hemodynamic
Invasive Hemodynamic pulmonary catheter: PAS, PAD, mPAP, RA pressures, PCWP, CI, RVSWi (calculated), TPG, PVR, and SvO2
Efficacy - Echocardiographic
Echocardiographic RV dimensions RV systolic functional assessment Tricuspid valve regurgitation Pulmonary Vascular resistance

Full Information

First Posted
May 6, 2011
Last Updated
August 30, 2023
Sponsor
University of Nebraska
Collaborators
Thoratec Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT01571037
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
April 5, 2012 (Actual)
Primary Completion Date
February 1, 2013 (Actual)
Study Completion Date
February 21, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nebraska
Collaborators
Thoratec Corporation

4. Oversight

Data Monitoring Committee
Yes

5. 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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Heart Disease, Right Ventricular Dysfunction
Keywords
mechanical circulatory assist device

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
inhaled nebulized Milrinone
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Inhaled, nebulized, Milrinone
Other Intervention Name(s)
Primacor
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
inhaled nebulized milrinone
Other Intervention Name(s)
Primacor
Intervention Description
0.5 mg/ml inhaled nebulized milrinone deliver at 12 ml/hr continuously until either 24 hours or extubated.
Primary Outcome Measure Information:
Title
Safety: Incidence of Arrhythmias, Hypotension and Hypersensitivity Reaction
Description
Arrhythmias: Atrial Ventricular 'Sustained' hypotension Hypersensitivity reaction to milrinone
Time Frame
12 and 24 hours
Secondary Outcome Measure Information:
Title
Efficacy - Hemodynamic
Description
Invasive Hemodynamic pulmonary catheter: PAS, PAD, mPAP, RA pressures, PCWP, CI, RVSWi (calculated), TPG, PVR, and SvO2
Time Frame
30, 60 minutes, then every 4 hours thereafter
Title
Efficacy - Echocardiographic
Description
Echocardiographic RV dimensions RV systolic functional assessment Tricuspid valve regurgitation Pulmonary Vascular resistance
Time Frame
Pre-op Echocardiography, intraoperative TEE (before and after inhaled milrinone) and postoperative Echocardiography within 48 hours of milrinone initiation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas A Haglund, MD
Organizational Affiliation
University of Nebraska
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-2265
Country
United States

12. IPD Sharing Statement

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

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