Inhaled Milrinone and Epoprostenol for the Prevention of Difficult Cardiac Pulmonary Bypass Separation

NCT05450328 | Not Yet Recruiting Phase 2

• 1 other identifier: ICM 2022-3026
• Study Type: interventional
• Target: 141
• Locations: 0 countries
• Sites: N/A

Brief Summary

In cardiac surgery, the presence of pulmonary hypertension (PH) is a prognostic factor associated with increased mortality and morbidity. In this context, one of the main causes of PH is related to reperfusion ischemia during weaning from extracorporeal circulation (CPB). One of the consequences of PH is right ventricular dysfunction. During weaning from CPB, the development of a right ventricular dysfunction is associated with increased requirements for vasopressor and inotropic agents, duration of mechanical ventilation, prolonged intensive care and hospital stay, and increased mortality compared with patients with left ventricular (LV) dysfunction. The management of patients with PH with or without right ventricular (RV) dysfunction relies on several strategies such as the administration of intravenous and inhaled agents, or mechanical ventricular support. Among those agents, the administration of inotropes or pulmonary vasodilators such as epoprostenol, milrinone and nitric oxide are among the most widely used treatments recommended by the Canadian Cardiovascular Society. At the Montreal Heart Institute, inhaled epoprostenol and milrinone are routinely administered to patients with PH or LV dysfunction in the perioperative setting. Despite the frequent use of inhaled epoprostenol and milrinone, Health Canada has not yet approved the use of these molecules. The primary objective of this multicenter, double-blind, randomized clinical trial is to evaluate the clinical efficacy of the combined administration of inhaled epoprostenol and milrinone in a cardiac surgery setting. This trial will compare the clinical outcome of 71 patients who will receive inhaled epoprostenol and milrinone before the start of bypass surgery to 71 patients who will receive a placebo before the start of the CPB. The primary clinical outcome is the proportion of patients with an "unsuccessful" CPB weaning defined by the use of an inotrope +/- vasopressor agent or the use of mechanical circulatory support or a return to bypass grafting for hemodynamic reasons. This clinical trial will evaluate the clinical efficacy of the combination of inhaled agents in a cardiac surgery setting. Therefore, if the results of this study are positive, the combination of inhaled epoprostenol and milrinone will optimize the management of patients with pulmonary hypertension with or without a right ventricular dysfunction.

Conditions

Right Heart Failure; Right Ventricular Dysfunction

Keywords

Cardiac Surgery; Right Ventricular Dysfunction; Cardiopulmonary Bypass; Inhaled Therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who have a difficult CPB weaning in both groups

  To determine whether the use of inhaled Epoprostenol and Milrinone, prior to the initiation of CPB, decreases the occurrence of difficult CPB weaning compared to placebo administration.

  1 year

Secondary Outcomes (14)

• Correlation between the variation of central venous pressure and patients who received the treatment

  1 year

• Correlation between the variation of cardiac output and patients who received the treatment

  1 year

• Correlation between the variation of arterial pressure and patients who received the treatment

  1 year

• Correlation between the right ventricular curve etiology (normal, square root, oblique) and patients who received the treatment

  1 year

• Correlation between the PAM/ PAPM ratio taken at T0 and T1 and patients who received the treatment

  1 year

Study Arms (2)

Normal Saline

PLACEBO COMPARATOR

The control group will receive a saline solution (8mL) as a placebo, before CPB start.

Drug: Normal saline

Combination of inhaled Epoprostenol and Milrinone

ACTIVE COMPARATOR

The experimental group will receive simultaneously 4mg of Milrinone (1mg/mL, 4mL) and 60 mcg of Epoprostenol (15 mcg/mL, 4mL) before CPB initiation.

Drug: Combined Epoprostenol Sodium & Milrinone

Interventions

Combined Epoprostenol Sodium & Milrinone DRUG

One syringe containing 4mg of milrinone (1mg/mL, 4mL) and one syringe containing 60 mcg of epoprostenol (15 mcg/mL, 4mL). The drugs will be administered via an ultrasonic nebulizer (Aeroneb Professional Nebulizer System, Aerogen Ltd, Galway, Ireland, registration number: 66728) over a period of 20 minutes. This type of nebulizer is used routinely at the Montreal Heart Institute and can hold a maximum of 8 mL of solutions.

Combination of inhaled Epoprostenol and Milrinone

Normal saline DRUG

The control group will receive two syringes of 4mL of Normal Saline, before CPB start. The placebo will be administered via an ultrasonic nebulizer (Aeroneb Professional Nebulizer System, Aerogen Ltd, Galway, Ireland, registration number: 66728) over a period of 20 minutes. This type of nebulizer is used routinely at the Montreal Heart Institute and can hold a maximum of 8 mL of solutions.

Normal Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Only patients undergoing cardiac surgery with CPB and aged 18 years and older will be included in this study.

You may not qualify if:

• The presence of congenital cardiomyopathy, which the correction is the primary objective of the proposed surgery. For example, a patient who requires surgery for atrial septal defect closure only would not be eligible for the study. On the other hand, a patient who undergoes this same surgery in addition to a valve replacement, for example, would be eligible to participate in the study.
• Heart transplant or ventricular assist device surgery
• Urgent surgery including hemodynamic instability requiring vasopressor agents upon arrival in the operating room
• A contraindication to transesophageal ultrasound monitoring or the presence of an unstable cervical spine.
• Presence of a contraindication related to Epoprostenol or Milrinone administration such as a documented left ventricular or right ventricular outflow tract obstruction, a severe unaddressed aortic stenosis, or a documented allergy to either of these two molecules.

Sponsors & Collaborators

• Montreal Heart Institute: lead

Related Publications (23)

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MeSH Terms

Conditions

Heart Failure; Ventricular Dysfunction, Right

Interventions

Milrinone; Saline Solution

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Amrinone; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Stephanie Jarry, PhD (c)

CONTACT

5149289258; stephanie.jarry.1@umontreal.ca

André Denault, MD, PhD

CONTACT

5143763330; andre.denault@umontreal.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: July 8, 2022
• Study Start: November 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share