scholarly journals Statistical analysis plan for the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial

2021 ◽  
Vol 23 (1) ◽  
pp. 47-58
Author(s):  
Kristen S Gibbons ◽  
◽  
Luregn J Schlapbach ◽  
Kerry Johnson ◽  
Stephen B Horton ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Statistical Analysis ◽  
Cardiopulmonary Bypass ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Statistical Tests ◽  
Heart Defects ◽  
Statistical Analysis Plan ◽  
Statistical Analyses ◽  
Secondary Outcome

Abstract Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses. Trial registration: ACTRN12617000821392

Effects of cardiopulmonary bypass and inhaled nitric oxide on platelets in children with congenital heart defects

1998 ◽  
Vol 157 (3) ◽  
pp. 194-201 ◽  
Author(s):  
J. Breuer ◽  
G. Leube ◽  
P. Mayer ◽  
S. Gebhardt ◽  
L. Sieverding ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiopulmonary Bypass ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Inhaled Nitric Oxide

Time Course of Endothelin-1 and Nitrate Anion Levels After Cardiopulmonary Bypass in Congenital Heart Defects

1997 ◽  
Vol 63 (3) ◽  
pp. 648-652 ◽  
Author(s):  
Takeshi Hiramatsu ◽  
Yasuharu Imai ◽  
Yoshinori Takanashi ◽  
Shuichi Hoshino ◽  
Masafumi Yashima ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Time Course ◽  
Heart Defects ◽  
Nitrate Anion ◽  
Endothelin 1

scholarly journals Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 436 ◽  
Author(s):  
Engineer ◽  
Saiyin ◽  
Greco ◽  
Feng
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Defects ◽  
Maternal Diabetes ◽  
Embryonic Heart ◽  
Pregestational Diabetes ◽  
Enos Uncoupling

Congenital heart defects (CHDs) are the most prevalent and serious birth defect, occurring in 1% of all live births. Pregestational maternal diabetes is a known risk factor for the development of CHDs, elevating the risk in the child by more than four-fold. As the prevalence of diabetes rapidly rises among women of childbearing age, there is a need to investigate the mechanisms and potential preventative strategies for these defects. In experimental animal models of pregestational diabetes induced-CHDs, upwards of 50% of offspring display congenital malformations of the heart, including septal, valvular, and outflow tract defects. Specifically, the imbalance of nitric oxide (NO) and reactive oxygen species (ROS) signaling is a major driver of the development of CHDs in offspring of mice with pregestational diabetes. NO from endothelial nitric oxide synthase (eNOS) is crucial to cardiogenesis, regulating various cellular and molecular processes. In fact, deficiency in eNOS results in CHDs and coronary artery malformation. Embryonic hearts from diabetic dams exhibit eNOS uncoupling and oxidative stress. Maternal treatment with sapropterin, a cofactor of eNOS, and antioxidants such as N-acetylcysteine, vitamin E, and glutathione as well as maternal exercise have been shown to improve eNOS function, reduce oxidative stress, and lower the incidence CHDs in the offspring of mice with pregestational diabetes. This review summarizes recent data on pregestational diabetes-induced CHDs, and offers insights into the important roles of NO and ROS in embryonic heart development and pathogenesis of CHDs in maternal diabetes.

Optimizing response of the neonate and infant to cardiopulmonary bypass

2005 ◽  
Vol 15 (S1) ◽  
pp. 142-148 ◽  
Author(s):  
Ross M. Ungerleider
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Normal Anatomy ◽  
Complete Repair ◽  
Innovative Techniques

The evolution of cardiac surgery has led to increasing emphasis on complete repair of congenital heart defects early in life, nowadays increasingly performed in neonates or small infants. Good results have been achieved because of innovative techniques permitting reconstruction of normal anatomy, and restoration of normal physiology, before either the heart or the patient undergo deleterious adaptation to the congenitally abnormal physiology. Despite the ability surgically to correct complex defects in such small patients, limitations in outcome are sometimes encountered related to the systems necessary for repair. In particular, exposure to cardiopulmonary bypass may present the greatest challenge for these tiny patients.

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

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e026664 ◽  
Author(s):  
Luregn J Schlapbach ◽  
Stephen Brian Horton ◽  
Debbie Amanda Long ◽  
John Beca ◽  
Simon Erickson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiopulmonary Bypass ◽  
Standard Care ◽  
Congenital Heart ◽  
Heart Defects ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Double Blind ◽  
Low Cardiac Output Syndrome ◽  
The Impact

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

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