Speaker
Luregn Schlapbach, PhD, FCICM
Head, Department of Intensive Care and Neonatology
University Children`s Hospital, Zurich
Zurich, Switzerland
The University of Queensland
Brisbane, Australia
Keywords
Pediatric, Pragmatic Clinical Trial, Congenital Heart Disease
Key Points
- The focus of the NITRIC file was on congenital heart disease, which affects about 1 in 100 newborn children with 25 percent requiring surgery before age 2. One of the main challenges of cardiac surgery, in addition to the technical complexities, is the occurrence of low cardiac output syndrome.
- The NITRIC Trial was a double blind, multicenter, randomized, parallel-group trial recruiting at 6 pediatric cardiac surgical centers in Australia, New Zealand, and The Netherlands. All infants and children less than 2 years of age undergoing open heart surgery on cardiopulmonary bypass were eligible for the study with exclusions for diseases that implied high severity pre-bypass.
- The intervention was applied by perfusionists at a steady concentration from the start until the end of bypass. All other surgical staff were blinded. There was no use of nitric oxide (NO) during CPB controls. All patients could receive inhalation NO during/after surgery if considered indicated by the treatment team. There was no change in perioperative care. There was no prescription of pre-surgical, anesthetic, surgical, perfusion, and ICU management procedures.
- The primary outcome was ventilator-free days (VFD) from start of cardiopulmonary bypass to day 28, with a number of secondary outcomes. The recruitment began in July 2017-April 2022 and 71 percent of approached parents provided consent. 1,371 patients were randomized with 1,364 in the final analysis.
- The hypothesis was that patients with nitric oxide would recover quicker allowing for more ventilator-free days, but there was no difference between the intervention and standard of care. There was no difference in the secondary outcomes either.
- There were a number of limitations. This was not a dose finding trial and no nitrosothiol compounds were measured; the perfusionists in the study were not blinded; we allowed open label iNO; the choice of ventilator-free days as a primary endpoint can be criticized.
Discussion Themes
– Can we learn the most important lessons from our trials sooner, that a particular intervention is not achieving what was hoped, with the idea that it will provide greater bandwidth of the research enterprise? Of course, you wonder is it justified to spend all of the resources for something that was negative. Our study gave us a unique power to understand what happens after newborn cardiac surgeries. The design of platform trials can build on the lessons learned from this study.
– Why didn’t you start to design the follow-on trial while you were still in the field? COVID-19 absorbed everyone in the middle of the trial. We had to concentrate a lot to even be able to finish the trial, to talk to parents and consent for the study.
Tags
#pctGR, @Collaboratory1