BMJ Open (Aug 2019)

Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial

  • Yves d’Udekem,
  • Simon Erickson,
  • Marino Festa,
  • Stephen Brian Horton,
  • Debbie Amanda Long,
  • John Beca,
  • Nelson Alphonso,
  • Kerry Johnson,
  • Carmel Delzoppo,
  • Kim van Loon,
  • B Gannon,
  • Jonas Fooken,
  • Antje Blumenthal,
  • Warwick Butt,
  • Steve Horton,
  • Johnny Millar,
  • David Buckley,
  • Taryn Evans,
  • Claire Sherring,
  • John Artrip,
  • Killian O’Shaughnessy,
  • Rebecca Fletcher,
  • Simon Byrne,
  • Sam Barr,
  • Rae Kelly,
  • Deborah Long,
  • Kerry Johnston,
  • Carla Zuzak,
  • Benjamin Anderson,
  • Kim van Loon,
  • Nicole J C W van Belle-van Haaren,
  • Bram van Wijk,
  • Erik Koomen

DOI
https://doi.org/10.1136/bmjopen-2018-026664
Journal volume & issue
Vol. 9, no. 8

Abstract

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IntroductionCongenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol.Methods and analysisThe NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery.Ethics and disseminationThe study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal.Trial registration numberACTRN12617000821392