Prophylactic Use of Milrinone After Congenital Heart Surgery in Infants

Cardiac Surgical Procedures Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03823781
• Other study ID #: SCMCIRB-K2018105
• Status: Recruiting
• Phase: Phase 3
• Start date: February 2019
• Est. completion date: July 2021

Study information

• Verified date: January 2019
• Source: Shanghai Children's Medical Center
• Contact: Jihong Huang, MD, PhD
• Phone: +8618930830766
• Email: huangjihong[@]scmc.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 520
• Est. completion date: July 2021
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Months

Eligibility

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• Consent was withdrawn by participants' parent or guardian.

Related Conditions & MeSH terms

• Cardiac Output, Low
• Cardiac Surgical Procedures
• Infant
• Low Cardiac Output Syndrome
• Syndrome

Intervention

Drug:
• Milrinone
The study intervention is an intravenous infusion of milrinone or placebo.
• Normal saline
The study intervention is an intravenous infusion of milrinone or placebo.

Locations

Country	Name	City	State
China	Shanghai Shanghai Children's Medical Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Children's Medical Center

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants died within 30 days postoperatively		up to 30 days postoperatively
Primary	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	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of participants requiring mechanical circulatory support.	eg. Extra-Corporeal Membrane Oxygenation, ventricular assist device	up to 30 days postoperatively
Secondary	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
Secondary	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