Nitric Oxide During Bypass for Arterial Switch Operation

NCT03661385 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: 38017ACTRN12618000089235p
• Study Type: interventional
• Target: 300
• Locations: 4 countries
• Sites: 4

Brief Summary

This trial will test if adding nitric oxide (NO) gas to the cardiopulmonary bypass (CPB) circuit in infants undergoing an arterial switch operation (ASO) for Transposition of the Great Arteries (TGA) changes the incidence of major postoperative adverse events (AEs). Major postoperative AEs include cardiac arrest, emergency chest opening, use of ECMO (machine that acts as an artificial heart and lung during surgery), and death. Participants will be randomised to receive oxygen plus nitric oxide (intervention arm) or oxygen without nitric oxide (control arm) during CPB.

Conditions

Low Cardiac Output Syndrome; Transposition of Great Vessels

Keywords

Cardiopulmonary bypass; Congenital heart disease; Low cardiac output syndrome; Nitric oxide; Transposition of Great Arteries; Arterial switch operation

Outcome Measures

Primary Outcomes (1)

• Major adverse events

  The primary outcome is the number of participants with major adverse events (MAEs) within 28 days post-operatively. MAEs include cardiac arrest, emergency chest opening, use of ECMO, and death.

  28 days post intervention

Secondary Outcomes (9)

• Length of stay in ICU (hours)

  This will be calculated from date and time of admission to ICU to date and time of discharge from ICU in hours up to 28 days

• Length of stay in hospital (days)

  28 days (or until hospital discharge)

• Ventilator-free days

  28 days (or until ICU discharge)

• Inotrope hours

  Number of hours inotropes have been administered during first 28 days post operatively

• Dialysis-free days

  28 days (or until ICU discharge)

Study Arms (2)

Intervention arm

ACTIVE COMPARATOR

• Intervention arm will receive nitric oxide 20 parts per million (ppm) into the oxygenator of a cardio-pulmonary bypass circuit

Drug: Nitric Oxide

Control arm

NO INTERVENTION

Control arm will not receive nitric oxide, they will receive standard bypass as per local policy

Interventions

Nitric Oxide DRUG

Addition of nitric oxide 20ppm into bypass circuit

Intervention arm

Eligibility Criteria

• Age: 0 Days+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Each participant must meet all of the following criteria to be enrolled in this study:
• Infant aged greater than or equal to 36 weeks gestation
• Infants less than 2 years
• Diagnosed with TGA and requiring Arterial Switch Operation
• Consent of parents/guardian.

You may not qualify if:

• Potential participants will be excluded if they meet any of the following criteria:
• They have multiple major congenital anomalies (anomalies which affect the infant's life expectancy or health status)
• They have multiple other cardiac abnormalities (with the exception of ASD, VSD or PDA)
• They weigh less than 2.2kgs.
• Prior surgical exposure to cardio-pulmonary bypass

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead

Study Sites (4)

Royal Children's Hospital

Melbourne, Victoria, 3050, Australia

Location

Stollery Cildren's Hospital

Edmonton, Alberta, AB T6G 2B7, Canada

Location

Harapan Kita Children and Women's Hospital

Jakarta, Indonesia

Location

Institut Jantung Negara

Kuala Lumpur, 50400, Malaysia

Location

Related Publications (6)

• Chello M, Mastroroberto P, Perticone F, Celi V, Colonna A. Nitric oxide modulation of neutrophil-endothelium interaction: difference between arterial and venous coronary bypass grafts. J Am Coll Cardiol. 1998 Mar 15;31(4):823-6. doi: 10.1016/s0735-1097(97)00560-3.

  PMID: 9525554 BACKGROUND

• Hataishi R, Rodrigues AC, Neilan TG, Morgan JG, Buys E, Shiva S, Tambouret R, Jassal DS, Raher MJ, Furutani E, Ichinose F, Gladwin MT, Rosenzweig A, Zapol WM, Picard MH, Bloch KD, Scherrer-Crosbie M. Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H379-84. doi: 10.1152/ajpheart.01172.2005. Epub 2006 Jan 27.

  PMID: 16443673 BACKGROUND

• Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg. 2003 Feb;75(2):S715-20. doi: 10.1016/s0003-4975(02)04701-x.

  PMID: 12607717 BACKGROUND

• Zahler S, Massoudy P, Hartl H, Hahnel C, Meisner H, Becker BF. Acute cardiac inflammatory responses to postischemic reperfusion during cardiopulmonary bypass. Cardiovasc Res. 1999 Mar;41(3):722-30. doi: 10.1016/s0008-6363(98)00229-6.

  PMID: 10435044 BACKGROUND

• Checchia PA, Bronicki RA, Muenzer JT, Dixon D, Raithel S, Gandhi SK, Huddleston CB. Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children--a randomized trial. J Thorac Cardiovasc Surg. 2013 Sep;146(3):530-6. doi: 10.1016/j.jtcvs.2012.09.100. Epub 2012 Dec 8.

  PMID: 23228403 RESULT

• James C, Millar J, Horton S, Brizard C, Molesworth C, Butt W. Nitric oxide administration during paediatric cardiopulmonary bypass: a randomised controlled trial. Intensive Care Med. 2016 Nov;42(11):1744-1752. doi: 10.1007/s00134-016-4420-6. Epub 2016 Sep 30.

  PMID: 27686343 RESULT

MeSH Terms

Conditions

Cardiac Output, Low; Transposition of Great Vessels; Heart Defects, Congenital

Interventions

Nitric Oxide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals

Study Officials

• Warwick Butt

  MRCI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Perfusionist (operating bypass) is unblinded to randomisation. They will randomize patient in a computer base (REDcap).Randomization is blinded to all other staff and the nitric oxide container is draped. Nitric oxide container will be attached in all cases.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blinded, randomised controlled, parallel study comparing an intervention with a control.

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: September 7, 2018
• Study Start: July 11, 2018
• Primary Completion: March 23, 2022
• Study Completion: April 23, 2023
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); ID (1); MY (1); CA (1)