@article{064a7f6e40074eae9b6790a733aec4a0,
title = "Rationale and design of the STeroids to REduce Systemic inflammation after infant heart Surgery (STRESS) trial",
abstract = "For decades, physicians have administered corticosteroids in the perioperative period to infants undergoing heart surgery with cardiopulmonary bypass (CPB) to reduce the postoperative systemic inflammatory response to CPB. Some question this practice because steroid efficacy has not been conclusively demonstrated and because some studies indicate that steroids could have harmful effects. STRESS is a randomized, placebo-controlled, double-blind, multicenter trial designed to evaluate safety and efficacy of perioperative steroids in infants (age < 1 year) undergoing heart surgery with CPB. Participants (planned enrollment = 1,200) are randomized 1:1 to methylprednisolone (30 mg/kg) administered into the CPB pump prime versus placebo. The trial is nested within the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database. The primary outcome is a global rank score of mortality, major morbidities, and hospital length of stay with components ranked commensurate with their clinical severity. Secondary outcomes include several measures of major postoperative morbidity, postoperative hospital length of stay, and steroid-related safety outcomes including prevalence of hyperglycemia and postoperative infectious complications. STRESS will be one of the largest trials ever conducted in children with heart disease and will answer a decades-old question related to safety and efficacy of perioperative steroids in infants undergoing heart surgery with CPB. The pragmatic “trial within a registry” design may provide a mechanism for conducting low-cost, high-efficiency trials in a heretofore-understudied patient population.",
author = "Hill, {Kevin D.} and Baldwin, {H. Scott} and Bichel, {David P.} and Butts, {Ryan J.} and Chamberlain, {Reid C.} and Ellis, {Alicia M.} and Graham, {Eric M.} and Jesse Hickerson and Hornik, {Christoph P.} and Jacobs, {Jeffrey P.} and Jacobs, {Marshall L.} and Jaquiss, {Robert DB} and Kannankeril, {Prince J.} and O'Brien, {Sean M.} and Rachel Torok and Turek, {Joseph W.} and Li, {Jennifer S.}",
note = "Funding Information: The STRESS trial (NCT03229538) is funded by a grant from the National Centers for Advancing Translational Sciences (NCATS, 1U01TR001803-01). Additional support is provided through collaborations with the NCATS-sponsored Trial Innovation Network (https://ncats.nih.gov/ctsa/projects/network, assisting with trial start-up, contracting and central institutional review board coordination) and the NICHD-sponsored Pediatric Trials Network (https://pediatrictrials.org/, assisting with PK/PD analyses). The Duke Clinical Research Institute is the primary data coordinating center, and Vanderbilt University serves as the central institutional review board. The trial is being conducted under the auspices of an FDA-issued Investigational New Drug Application (#129,266) from the Division of Cardiovascular and Renal Products, and written informed consent is obtained from parents or an authorized legal guardian before enrollment of each infant in the trial. An internal steering committee consisting of 4 pediatric cardiothoracic surgeons, 4 pediatric cardiologists, a pediatric cardiac intensivist, and a patient advocate provides continuous trial monitoring and oversight, whereas a 4-member external steering committee, including a pediatric cardiologist, a pediatric cardiothoracic surgeon, a pediatric cardiac intensivist, and a patient advocate, provides biannual trial review and oversight. An unblinded statistician is assigned to monitor trial safety. A DMC consisting of a pediatric cardiologist, a pediatric clinical trial specialist, and a biostatistician with expertise in congenital heart surgery will provide biannual and as-needed safety oversight in accordance with a DMC charter prepared and agreed upon prior to trial initiation.The STRESS trial is supported by grants from the National Centers for Advancing Translational Sciences (U01TR-001803-01, U24TR-001608-03) and from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U18FD-006298-02). Funding Information: Drs Hill, Baldwin, Bichel, Ellis, Jeffrey Jacobs, Marshall Jacobs, Kannankeril, O'Brien, and Li and Mr Hickerson receive support from the National Centers for Advancing Translational Sciences for their work in pediatric drug development (U01TR-001803-01). Dr Hornik receives salary support for research from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant 1K23HD090239) and the US government and industry for his work in pediatric and neonatal clinical pharmacology (government contract HHSN267200700051C). The content in this manuscript is solely the responsibility of the authors. Appendix A Funding Information: The STRESS trial is supported by grants from the National Centers for Advancing Translational Sciences ( U01TR-001803-01 , U24TR-001608-03 ) and from the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( U18FD-006298-02 ). Funding Information: The STRESS trial ( NCT03229538 ) is funded by a grant from the National Centers for Advancing Translational Sciences (NCATS, 1U01TR001803-01 ). Additional support is provided through collaborations with the NCATS-sponsored Trial Innovation Network ( https://ncats.nih.gov/ctsa/projects/network , assisting with trial start-up, contracting and central institutional review board coordination) and the NICHD-sponsored Pediatric Trials Network ( https://pediatrictrials.org/ , assisting with PK/PD analyses). The Duke Clinical Research Institute is the primary data coordinating center, and Vanderbilt University serves as the central institutional review board. The trial is being conducted under the auspices of an FDA-issued Investigational New Drug Application (#129,266) from the Division of Cardiovascular and Renal Products, and written informed consent is obtained from parents or an authorized legal guardian before enrollment of each infant in the trial. An internal steering committee consisting of 4 pediatric cardiothoracic surgeons, 4 pediatric cardiologists, a pediatric cardiac intensivist, and a patient advocate provides continuous trial monitoring and oversight, whereas a 4-member external steering committee, including a pediatric cardiologist, a pediatric cardiothoracic surgeon, a pediatric cardiac intensivist, and a patient advocate, provides biannual trial review and oversight. An unblinded statistician is assigned to monitor trial safety. A DMC consisting of a pediatric cardiologist, a pediatric clinical trial specialist, and a biostatistician with expertise in congenital heart surgery will provide biannual and as-needed safety oversight in accordance with a DMC charter prepared and agreed upon prior to trial initiation. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2020",
month = feb,
doi = "10.1016/j.ahj.2019.11.016",
language = "English (US)",
volume = "220",
pages = "192--202",
journal = "American heart journal",
issn = "0002-8703",
publisher = "Mosby Inc.",
}