Dataset Information

Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial: protocol for a two-centre, double-blind, randomised controlled trial in young children undergoing cardiac surgery.

ABSTRACT: INTRODUCTION:Myocardial protection against ischaemic-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, with current strategies, myocardial injury occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. Remote ischaemic preconditioning, the application of brief, non-lethal cycles of ischaemia and reperfusion to a distant organ or tissue, is a simple, low-risk and readily available technique which may improve myocardial protection. The Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial will assess whether remote ischaemic preconditioning, applied to both lower limbs immediately prior to surgery, reduces myocardial injury in cyanotic and acyanotic young children. METHODS AND ANALYSIS:The BRICC trial is a two-centre, double-blind, randomised controlled trial recruiting up to 120 young children (age 3 months to 3 years) undergoing primary repair of tetralogy of Fallot or surgical closure of an isolated ventricular septal defect. Participants will be randomised in a 1:1 ratio to either bilateral remote ischaemic preconditioning (3×5?min cycles) or sham immediately prior to surgery, with follow-up until discharge from hospital or 30 days, whichever is sooner. The primary outcome is reduction in area under the time-concentration curve for high-sensitivity (hs) troponin-T release in the first 24?hours after aortic cross-clamp release. Secondary outcome measures include peak hs-troponin-T, vasoactive inotrope score, arterial lactate and central venous oxygen saturations in the first 12?hours, and lengths of stay in the paediatric intensive care unit and the hospital. ETHICS AND DISSEMINATION:The trial was approved by the West Midlands-Solihull National Health Service Research Ethics Committee (16/WM/0309) on 5 August 2016. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Parents will be informed of the results through a newsletter in conjunction with a local charity. TRIAL REGISTRATION NUMBER:ISRCTN12923441.

SUBMITTER: Drury NE

PROVIDER: S-EPMC7542918 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial: protocol for a two-centre, double-blind, randomised controlled trial in young children undergoing cardiac surgery.

Drury Nigel E NE Bi Rehana R Woolley Rebecca L RL Stickley John J Morris Kevin P KP Montgomerie James J van Doorn Carin C Dunn Warwick B WB Madhani Melanie M Ives Natalie J NJ Kirchhof Paulus P Jones Timothy J TJ

BMJ open 20201007 10

<h4>Introduction</h4>Myocardial protection against ischaemic-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, with current strategies, myocardial injury occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. Remote ischaemic preconditioning, the application of brief, non-lethal cycles of ischaemia and reperfusion to a distant organ or tissue, is a simple, low-risk and r ...[more]

PMID: 33033035

Similar Datasets

Project description:AimsRemote ischaemic preconditioning (RIPC) by inducing brief ischaemia in distant tissues protects the heart against myocardial ischaemia-reperfusion injury (IRI) in children undergoing open-heart surgery, although its effectiveness in adults with comorbidities is controversial. The effectiveness and mechanism of RIPC with respect to myocardial IRI in children with tetralogy of Fallot (ToF), a severe cyanotic congenital cardiac disease, undergoing open heart surgery are unclear. We hypothesized that RIPC can confer cardioprotection in children undergoing ToF repair surgery.Methods and resultsOverall, 112 ToF children undergoing radical open cardiac surgery using cardiopulmonary bypass (CPB) were randomized to either a RIPC group (n = 55) or a control group (n = 57). The RIPC protocol consisted of three cycles of 5-min lower limb occlusion and 5-min reperfusion using a cuff-inflator. Serum inflammatory cytokines and cardiac injury markers were measured before surgery and after CPB. Right ventricle outflow tract (RVOT) tissues were collected during the surgery to assess hypoxia-inducible factor (Hif)-1α and other signalling proteins. Cardiac mitochondrial injury was assessed by electron microscopy. The primary results showed that the length of stay in the intensive care unit (ICU) was longer in the control group than in the RIPC group (52.30 ± 13.43 h vs. 47.55 ± 10.34 h, respectively, P = 0.039). Patients in the control group needed longer post-operative ventilation time compared to the RIPC group (35.02 ± 6.56 h vs. 31.96 ± 6.60 h, respectively, P = 0.016). The levels of post-operative serum troponin-T at 12 and 18 h, CK-MB at 24 h, as well as the serum h-FABP levels at 6 h, after CPB were significantly lower, which was coincident with significantly higher protein expression of cardiac Hif-1α, p-Akt, p-STAT3, p-STAT5, and p-eNOS and less vacuolization of mitochondria in the RIPC group compared to the control group.ConclusionIn ToF children undergoing open heart surgery, RIPC attenuates myocardial IRI and improves the short-term prognosis.

Project description:BackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Project description:IntroductionChildren with unilateral cerebral palsy (UCP) have difficulty in bimanual coordination that restricts the child's independence in daily activities. Although several efficacious interventions to improve bimanual coordination exist, these interventions often require higher training doses and have modest effect sizes. Thus, there is a critical need to find an effective priming agent that, when paired with task-specific training, will facilitate neurobiological processes to enhance the magnitude of training effects and subsequently improve functional capabilities of children with UCP. The aim of this study is to determine the effects of a novel priming agent, remote ischaemic conditioning (RIC), combined with bimanual training on bimanual skill learning and corticospinal excitability in children with UCP.Methods and analyses46 children, aged 8-16 years, will be randomly assigned to receive RIC or sham conditioning combined with 5 days of bimanual skill (cup stacking) training (15 trials per session). RIC or sham conditioning will be performed with a standard conditioning protocol of five cycles of alternative inflation and deflation of a pressure cuff on the affected arm with the pressure of at least 20 mm Hg above systolic blood pressure for RIC and 25 mm Hg for sham conditioning. Primary outcomes will be movement time and corticospinal excitability measures determined with a single-pulse transcranial magnetic stimulation (TMS). Secondary outcomes include Assisting Hand Assessment, spatio-temporal kinematic variables and paired pulse TMS measures. All measures will be conducted before and immediately after the intervention. A mixed model analysis of variance will test the group×time interaction for all outcomes with group (RIC and sham) as between-subject and time (preintervention, postintervention) as within-subject factors.Ethics and disseminationThe study has been approved by the University Medical Centre Institutional Review Board (UMCIRB #21-001913). We will disseminate the study findings via peer-reviewed publications and presentations at professional conferences.Trial registration numberNCT05777070.

Dataset Information

Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial: protocol for a two-centre, double-blind, randomised controlled trial in young children undergoing cardiac surgery.

Publications

Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial: protocol for a two-centre, double-blind, randomised controlled trial in young children undergoing cardiac surgery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets