Inhaled Versus Intravenous Milrinone for Patients Undergoing Mitral Valve Replacement Surgery

NCT05838846 | Completed Phase 2

• 1 other identifier: 2/2023 ANET 60
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective open-label randomized study aims to compare the effect of inhaled versus intravenous milrinone on the pulmonary vascular resistance in patients undergoing mitral valve replacement surgery. The primary outcome is to determine change in pulmonary artery pressure. The secondary outcomes include,

• Incidence of systemic hypotension.
• Hemodynamic affection and need of vasopressors and inotropes.
• Change in pulmonary vascular resistance versus systemic vascular resistance.
• Right ventricular function.
• Duration of mechanical ventilation.
• Need for mechanical circulatory support devices.
• Urine output
• Length of intensive care (ICU) in stay. As the investigators hypothesize that inhaled milrinone has a selective pulmonary vasodilator effect devoid of the systemic hypotension with the intravenous administration.

Conditions

Mitral Valve Replacement; Pulmonary Hypertension; Inhaled Milrinone; Intravenous Milrinone

Keywords

Milrinone; Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in pulmonary artery pressure

  Intraoperative

Secondary Outcomes (7)

• Incidence of systemic hypotension

  Intraoperative

• Hemodynamic affection and need of vasopressors and inotropes.

  Intraoperative

• Pulmonary vascular resistance versus systemic vascular resistance

  Intraoperative

• Right ventricular function

  Intraoperative

• Duration of mechanical ventilation

  Postoperative in ICU (up to 24 hours)

Study Arms (2)

Group A (iMil)

EXPERIMENTAL

Patients will receive 2 doses of inhaled milrinone at the following time points (after sternotomy and after aortic cross clamp off) at dosage of 50 mcg/kg by nebulization, inhaled milrinone will be administered through Aerogen solo with Pro-X controller - continuous mode- attached to ventilator circuit distal to viral/ bacterial heat and moisture exchange filter. Then pulmonary vascular resistance and systemic vascular resistance will be calculated after first dose ended by 2 minutes and after second dose ended by 15 minutes till stabilization of post CPB other variables like temperature and acid-base status, both measurements will be done while using inspired oxygen of 0.80.

Drug: Inhaled Milrinone

Group B (IvMil)

ACTIVE COMPARATOR

Patients will receive intravenous milrinone - started after induction of anesthesia - infusion at dosage of 0.3 - 0.75 mcg/kg/min after loading dose of 50 mic/kg over 10 min. After cross clamp off and temperature of 32 degree, Pulmonary vascular resistance and systemic vascular resistance will be calculated at the same corresponding time points to group A.

Drug: IV Milrinone

Interventions

Inhaled Milrinone DRUG

Patients will receive 2 doses of inhaled milrinone at the following time points (after sternotomy and after aortic cross clamp off) at dosage of 50 mcg/kg by nebulization, inhaled milrinone will be administered through Aerogen solo with Pro-X controller - continuous mode- attached to ventilator circuit distal to viral/ bacterial heat and moisture exchange filter.

Group A (iMil)

IV Milrinone DRUG

Patients will receive intravenous milrinone infusion at dosage of 0.3 - 0.75 mcg/kg/min with loading dose of 50 mcg/kg over 10 min. After cross clamp off and temperature of 32 degree, Pulmonary vascular resistance and systemic vascular resistance will be calculated at the same corresponding time points to group A.

Group B (IvMil)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Severe mitral regurgitation and moderate or severe pulmonary hypertension
• Scheduled for mitral valve replacement surgery
• \# Criteria of severe mitral regurgitation:
• Central jet MR \>40% LA or holosystolic eccentric jet MR
• Vena contracta ≥ 0.7 cm
• Regurgitant volume ≥60 ml
• Regurgitant fraction ≥50%
• EROA ≥0.40 cm2
• \# Criteria of moderate and severe pulmonary hypertension:
• Moderate pulmonary hypertension; mean pulmonary artery pressure \> 41 mmHg while, severe pulmonary hypertension; mean pulmonary artery pressure \> 55 mmHg
• Mean pulmonary artery pressure \> 40% of mean systemic blood pressure.
• Mean pulmonary artery pressure approximated from estimated systolic pulmonary artery pressure as following; mPAP= (estimated sPAP X 0.61) ± 2

You may not qualify if:

• Patients with aortic valvular lesions or pulmonary stenosis.
• Hemodynamic instability in the preoperative time (defined as acute requirement for vasoactive support or mechanical device).
• Contraindication to transesophageal echocardiography; esophageal stricture, tumor or diverticulum or active upper gastrointestinal bleeding
• Patients with hepatic or renal dysfunction.
• Patients with coagulopathy.
• Emergency surgeries.

Sponsors & Collaborators

• Menoufia University: lead

Study Sites (1)

Menoufia University Hospitals

Shibīn al Kawm, Menoufia, Egypt

Location

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

Milrinone

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Amrinone; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ghada A Hassan, Professor

  Faculty of Medicine - Menoufia University

  STUDY CHAIR

• Mohamed A Salem, A. Professor

  Faculty of Medicine - Menoufia University

  STUDY CHAIR

• Khaled M Gaballah, A. Professor

  Faculty of Medicine - Menoufia University

  STUDY CHAIR

• Mohammed O El Gouhary, Lecturer

  Faculty of Medicine - Ain Shams University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assisstant Lecturer Anesthesia, Intensive care and Pain management - Faculty of Medicie - Menoufia University

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: May 3, 2023
• Study Start: April 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: February 11, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)