Nebulized Inhaled Milrinone in a Hospitalized Advanced Heart Failure Population

NCT02077010 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 170530
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

Patients with end stage heart failure have significant symptoms (including fatigue and shortness of breath) which prevent them from being able to perform most activities of daily living. Milrinone is one of the inotropic medications that has been studied and used in the treatment of end stage heart failure. End stage heart failure patients awaiting a heart transplantation often have to be maintained on IV milrinone 24 hours a day through a chronic IV line. Two problems arise with this therapy. First, the IV line itself creates an opportunity for infection and blood clots, in addition to interfering with patient's quality of life. Second, patients may be exposed to higher levels of milrinone when given IV than are necessary for maintaining their heart's function. By doing this study the investigators hope to learn if a new way of giving HF patients milrinone can lower the levels of plasma milrinone which may lessen the chance of medication side effects, while still preserving the beneficial effects of milrinone. Additionally if the inhaled route of administration is effective patients may not need to have invasive IV lines to administer the medication (currently standard practice) which can cause other unwanted side effects.

Conditions

Heart Failure; Cardiomyopathy

Keywords

milrinone; heart failure; cardiomyopathy; inhaled

Outcome Measures

Primary Outcomes (7)

• Safety Analysis

  Safety analysis will consist of collecting patient reported adverse events around potential local (respiratory tree) adverse events resulting from the inhalation route and systemic adverse effects resulting from the effects of milrinone itself including ventricular tachycardia (VT), atrial arrhythmias, hypotension, and worsening hypoxia.

  A patient questionnaire to ascertain patient reported adverse events will be peformed at 24 hours

• Pharmacokinetic analysis

  Patient will have serial plasma samples drawn to determine inhaled milrinone pharmacokinetics. A total of six 0.5ml plasma samples will be obtained.

  Plasma samples will be drawn around the 4th inhaled dose and after the dose at the following time point of 0.5 hours to assess for serum milirinone concentration fro the trough to be no less than 50ng/ml and the peak to be no greater than 500ng/ml.

• Safety Analysis

  Safety analysis will consist of collecting patient reported adverse events

  A patient questionnaire to ascertain patient reported adverse events will be peformed at 48+/- 12 hours.

• Pharmacokinetic analysis

  Patient will have serial plasma samples drawn to determine inhaled milrinone pharmacokinetics. A total of six 0.5ml plasma samples will be obtained.

  Plasma samples will be drawn around the 4th inhaled dose and after the dose at the following time point of 1 hour to assess for serum milirinone concentration fro the trough to be no less than 50ng/ml and the peak to be no greater than 500ng/ml.

• Pharmacokinetic analysis

  Patient will have serial plasma samples drawn to determine inhaled milrinone pharmacokinetics. A total of six 0.5ml plasma samples will be obtained.

  Plasma samples will be drawn around the 4th inhaled dose and after the dose at the following time point of 2 hours to assess for serum milirinone concentration fro the trough to be no less than 50ng/ml and the peak to be no greater than 500ng/ml.

• Pharmacokinetic analysis

  Patient will have serial plasma samples drawn to determine inhaled milrinone pharmacokinetics. A total of six 0.5ml plasma samples will be obtained.

  Plasma samples will be drawn around the 4th inhaled dose and after the dose at the following time point of 4 hours to assess for serum milirinone concentration fro the trough to be no less than 50ng/ml and the peak to be no greater than 500ng/ml.

• Pharmacokinetic analysis

  Patient will have serial plasma samples drawn to determine inhaled milrinone pharmacokinetics. A total of six 0.5ml plasma samples will be obtained.

  Plasma samples will be drawn around the 4th inhaled dose and after the dose at the following time point of 8 hours to assess for serum milirinone concentration fro the trough to be no less than 50ng/ml and the peak to be no greater than 500ng/ml.

Secondary Outcomes (1)

• All cause mortality

  From date of randomization until study drug is completed (less than or equal to 72 hr after randomization)

Other Outcomes (7)

• Study Withdrawal Criteria -1

  From date of randomization until study drug is completed (less than or equal to 60 hr after randomization)

• Withdrawal criteria - 2

  From date of randomization until study drug is completed (less than or equal to 60 hr after randomization)

• Withdrawal criteria - 3

  From date of randomization until study drug is completed (less than or equal to 60 hr after randomization)

Study Arms (1)

Inhaled nebulized milrinone

EXPERIMENTAL

Inhaled nebulized milrinone 60mg/4ml every 8 hours using a jet nebulizer

Drug: Inhaled nebulized milrinone

Interventions

Inhaled nebulized milrinone DRUG

inhaled nebulized milrinone 60mg/4ml

Inhaled nebulized milrinone

Eligibility Criteria

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

You may qualify if:

• Patients age \> 18 years old
• Symptomatic Stage D heart failure requiring initiation of inotropic medication at the discretion of their cardiologist
• Signed informed consent

You may not qualify if:

• Patients incapable of signing informed consent for any reason
• Patients who are pregnant or breastfeeding
• Systolic blood pressure less than 85 mmHg prior to randomization
• Documented allergy or adverse reaction to milrinone

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• Vanderbilt University Medical Center: collaborator

Study Sites (2)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37204, United States

Location

MeSH Terms

Conditions

Heart Failure; Cardiomyopathies; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Zubair Shah, MD

  University of Kansas

  PRINCIPAL INVESTIGATOR

• Zachary L Cox, PharmD

  Vanderbilt University Medical Center/ Lipscomb University College of Pharmacy

  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: February 25, 2014
• First Posted: March 4, 2014
• Study Start: June 15, 2020
• Primary Completion: January 24, 2023
• Study Completion: January 24, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)