Prophylactic Use of Milrinone After Congenital Heart Surgery in Infants

Prophylactic Milrinone Infusion for the Prevention Low Cardiac Output Syndrome After Corrective Surgery for Congenital Heart Disease in Infants: A Randomized, Multi-center, Double-blinded, Placebo-controlled Study

This randomized, multi-center, double-blinded, placebo-controlled study is designed to evaluate the efficacy and safety of milrinone compared with placebo in participants after corrective surgery for congenital heart disease. Participants will be randomized in a 1:1 ratio within 90 minutes after arriving in the intensive care unit (ICU), to receive either intravenous milrinone or placebo for 36 hours. Participants will be stratified according Vasoactive Inotrope Score after arriving in the ICU.

Study Overview

• Status: Unknown
• Conditions: Infant; Cardiac Surgical Procedures; Low Cardiac Output Syndrome
• Intervention / Treatment: Drug: Milrinone; Drug: Normal saline

• Study Type: Interventional
• Enrollment (Anticipated): 520
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jihong Huang, MD, PhD; Phone Number: +8618930830766; Email: huangjihong@scmc.com.cn
• Study Contact Backup: Name: Zhuoming Xu, MD, PhD; Phone Number: +8618930830783; Email: xuzhuoming@scmc.com.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • Shanghai Shanghai Children's Medical Center
      • Contact: Jihong Huang, MD, PhD; Phone Number: +8618930830766; Email: huangjihong@scmc.com.cn
      • Contact: Chunxiang Li, MD; Phone Number: +8618916611383; Email: lichunxiang@scmc.com.cn
      • Principal Investigator: Huiwen Chen, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age younger than 12 months
• Without pre-operative low cardiac output syndrome
• Bi-ventricular repair of congenital heart disease involving cardiopulmonary bypass
• Informed consent obtained from each participant's parent or guardian

Exclusion Criteria:

• A body weight <2 kg
• Prematurity (birth <36 weeks postconceptual age)
• Renal dysfunction ( Creatinine>1.5mg/dL 48 hours before surgery)
• Low cardiac output syndrome or hypotension on arrival to ICU from OR
• Cardiopulmonary resuscitation before surgery
• Platelet count<80,000/mm3 before surgery
• Left ventricular outflow tract obstruction before surgery
• Ventricular arrhythmia before surgery
• Without femoral artery catheter before arriving in the ICU
• Consent was withdrawn by participants' parent or guardian.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: milrinone; milrinone milrinone will be administered intravenously at a rate of 0.75ug/kg/min for 35 hours, and baseline catecholamines will be administered at the discretion of the physician.	Drug: Milrinone; The study intervention is an intravenous infusion of milrinone or placebo.; Other Names: Milrinone Lactate
Placebo Comparator: normal saline; placebo placebo (normal saline) will be administered intravenously for 35 hours, and baseline catecholamines will be administered at the discretion of the physician.	Drug: Normal saline; The study intervention is an intravenous infusion of milrinone or placebo.; Other Names: Normal Saline 0.9% Infusion Solution Bag

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants died within 30 days postoperatively		up to 30 days postoperatively
Number of participants developed low cardiac output syndrome within the first 36 hours after initiation of study drug	Low cardiac output syndrome was defined as the following: clinical signs or symptoms (eg, tachycardia, oliguria, poor perfusion, or cardiac arrest) with or without a widened arterial-mixed venous oxygen saturation difference or metabolic acidosis; mechanical support of the circulation (eg, extracorporeal life support, ventricular assist device), a cardiac index determined by Pulse indicator continuous cardiac output (PiCCO) of <2.2 L/min/m2	36 hours after initiation of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants developed low cardiac output syndrome in the interval between 36 hours after initiation of study drug and the final Follow up. Cardiac index will be determined by Doppler echocardiography		up to 30 days postoperatively
Change in Vasoactive Inotrope Score.	Vasoactive Inotrope Score=100*Epinephrine dose (ug/kg/min)+100*Norepinephrine dose (ug/kg/min)+10*Dopamine dose (ug/kg/min)+10*Dobutamine dose (ug/kg/min) +10,000*Vasopressin dose (units/kg/min) +10*Milrinone dose (ug/kg/min)	36 hours after initiation of study drug
Length of intensive care stay.	Length of intensive care stay will be calculated from date of ICU admission to date of ICU discharge	up to 30 days postoperatively or until ICU discharge.
Length of hospital stay.	Length of hospital stay will be calculated from date of hospital admission to date of hospital discharge	up to 30 days postoperatively or until hospital discharge
Duration of mechanical ventilation.	Duration of mechanical ventilation will be calculated from date and time of ICU admission to date and time of extubation	up to 30 days postoperatively or until extubation
Number of participants with improvement of ventriculoarterial coupling	ventriculoarterial coupling improvement will be assessed by means of ventriculoarterial coupling values shift closer to 1. ventriculoarterial coupling will be obtained as : (1-EF)/EF	36 hours after initiation of study drug
Number of participants requiring mechanical circulatory support.	eg. Extra-Corporeal Membrane Oxygenation, ventricular assist device	up to 30 days postoperatively
Number of participants with a decrease in regional tissue oxygenation at least 20% from baseline.	Cerebral and abdominal regional tissue oxygenation will be monitored	36 hours after initiation of study drug
Number of participants with treatment-related adverse events	Treatment-related adverse events will be evaluated by sponsor's drug safety surveillance reviewer	36 hours after initiation of study drug

Collaborators and Investigators

• Sponsor: Shanghai Children's Medical Center
• Investigators: Study Director: Huiwen Chen, MD, PhD, Department of clinical research, Shanghai children's medical center

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2019
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: January 25, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Syndrome; Cardiac Output, Low; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Milrinone
• Other Study ID Numbers: SCMCIRB-K2018105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No