Prophylactic Use of Milrinone After Congenital Heart Surgery in Infants

Phase 3

• Conditions: Infant; Low Cardiac Output Syndrome; Cardiac Surgical Procedures
• Interventions: Drug: Normal saline; Drug: Milrinone

• Registration Number: NCT03823781
• Lead Sponsor: Shanghai Children's Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-01
• Study First Submitted: 2019-01-25
• Study First Submitted QC: 2019-01-29
• Last Update Submitted: 2019-01-29
• Study First Posted: 2019-01-30
• Last Update Posted: 2019-01-30
• Study Start: 2019-02
• Primary Completion: 2021-01
• Study Completion: 2021-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 520

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

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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• Consent was withdrawn by participants' parent or guardian.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
normal saline	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.
milrinone	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.

Primary Outcome Measures

Name	Time	Method
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	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

Secondary Outcome Measures

Name	Time	Method
Change in Vasoactive Inotrope Score.	36 hours after initiation of study drug	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)
Length of intensive care stay.	up to 30 days postoperatively or until ICU discharge.	Length of intensive care stay will be calculated from date of ICU admission to date of ICU discharge
Number of participants with improvement of ventriculoarterial coupling	36 hours after initiation of study drug	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
Length of hospital stay.	up to 30 days postoperatively or until hospital discharge	Length of hospital stay will be calculated from date of hospital admission to date of hospital discharge
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
Duration of mechanical ventilation.	up to 30 days postoperatively or until extubation	Duration of mechanical ventilation will be calculated from date and time of ICU admission to date and time of extubation
Number of participants requiring mechanical circulatory support.	up to 30 days postoperatively	eg. Extra-Corporeal Membrane Oxygenation, ventricular assist device
Number of participants with a decrease in regional tissue oxygenation at least 20% from baseline.	36 hours after initiation of study drug	Cerebral and abdominal regional tissue oxygenation will be monitored
Number of participants with treatment-related adverse events	36 hours after initiation of study drug	Treatment-related adverse events will be evaluated by sponsor's drug safety surveillance reviewer

Trial Locations

Locations (1)

Shanghai Shanghai Children's Medical Center; 🇨🇳 Shanghai, Shanghai, China