Introduction
Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is known to be responsible for ischaemia and reperfusion organ injury. In a previous study, ProMPT, in patients ...undergoing coronary artery bypass or aortic valve surgery we demonstrated improved cardiac protection when supplementing the cardioplegia solution with propofol (6 mcg/ml). The aim of the ProMPT2 study is to determine whether higher levels of propofol added to the cardioplegia could result in increased cardiac protection.
Methods and Analysis
The ProMPT2 study is a multi-centre, parallel, three-group, randomised controlled trial in adults undergoing non-emergency isolated coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 240 patients will be randomised in a 1:1:1 ratio to receive either cardioplegia supplementation with high dose of propofol (12 mcg/ml), low dose of propofol (6 mcg/ml) or placebo (saline). The primary outcome is myocardial injury, assessed by serial measurements of myocardial troponin T up to 48 hours after surgery. Secondary outcomes include biomarkers of renal function (creatinine) and metabolism (lactate).
Ethics and Dissemination
The trial received research ethics approval from South Central – Berkshire B Research Ethics Committee and Medicines and Healthcare products Regulatory Agency in September 2018. Any findings will be shared though peer-reviewed publications and presented at international and national meetings. Participants will be informed of results through patient organisations and newsletters.
Trial Registration
ISRCTN15255199. Registered in March 2019.
ObjectivesTo assess the effectiveness of injectable tissue pulmonary valve compared with standard pulmonary valve in patients requiring pulmonary valve replacement surgery.DesignA multicentre, ...single-blind, parallel two-group randomised controlled trial. Participants were blind to their allocation. Follow-up continued for 6 months. Randomised allocations were generated by a computer using block randomisation, stratified by centre.SettingTwo National Health Service secondary care centres in the UK.ParticipantsPeople aged 12–80 years requiring pulmonary valve replacement.InterventionsParticipants were randomly allocated (1:1 ratio) to injectable pulmonary valve replacement (IPVR) without cardiopulmonary bypass (CPB) or standard pulmonary valve replacement (SPVR) with CPB.Primary and secondary outcome measuresThe primary outcome was chest drainage volume over the first 24 hours after surgery. Secondary outcomes included in-hospital clinical outcomes; valve and heart function 6 months postsurgery and health-related quality of life 6 weeks and 6 months postsurgery.ResultsNineteen participants agreed to take part. Eleven were allocated to IPVR and eight to SPVR. The trial was stopped before the target sample size of 60 participants was reached due to challenges in recruitment. The primary analysis includes all randomised participants; there were no withdrawals. Chest drain volume 24 hours after surgery was on average 277.6 mL lower with IPVR (IPVR mean 340.0 mL; SPVR mean 633.8 mL; mean difference, −277.6; 95% CI, −484.0 to −71.2; p=0.005). There were no statistically significant differences in time to readiness for extubation (p=0.476), time to fitness for discharge (p=0.577) and time to first discharge from the intensive care unit (p=0.209). Six participants with IPVR required CPB. Safety profiles and quality of life scores were similar.ConclusionsIPVR reduced chest drain volume despite >50% of participants requiring CPB. There was no evidence of any other benefit of IPVR.Trial registration numberISRCTN23538073.
This study aimed to optimise techniques for whole transcriptome and small RNA analyses on clinical tissue samples from patients with cardiovascular disease. Clinical samples often represent a ...particular challenge to extracting RNA of sufficient quality for robust RNA sequencing analysis, and due to availability, it is rarely possible to optimise techniques on the samples themselves. Therefore, we have used equivalent samples from pigs undergoing cardiopulmonary bypass surgery to test different protocols for optimal RNA extraction, and then validated the protocols in human samples. Here we present an assessment of the quality and quantity of RNA obtained using a variety of commercially-available RNA extraction kits on both left ventricular biopsies and blood plasma. RNA extraction from these samples presents different difficulties; left ventricular biopsies are small and fibrous, while blood plasma has a low RNA content. We have validated our optimised extraction techniques on human clinical samples collected as part of the ARCADIA (Association of non-coding RNAs with Coronary Artery Disease and type 2 Diabetes) cohort study, resulting in successful whole transcriptome and small RNA sequencing of human left ventricular tissue.
Randomised controlled trials are often beset by problems with poor recruitment and retention. Information to support decisions on trial participation is usually provided as printed participant ...information sheets (PIS), which are often long, technical, and unappealing. Multimedia information (MMI), including animations and videos, may be a valuable alternative or complement to a PIS. The Trials Engagement in Children and Adolescents (TRECA) study compared MMI to PIS to investigate the effects on participant recruitment, retention, and quality of decision-making.
We undertook six SWATs (Study Within A Trial) within a series of host trials recruiting children and young people. Potential participants in the host trials were randomly allocated to receive MMI-only, PIS-only, or combined MMI + PIS. We recorded the rates of recruitment and retention (varying between 6 and 26 weeks post-randomisation) in each host trial. Potential participants approached about each host trial were asked to complete a nine-item Decision-Making Questionnaire (DMQ) to indicate their evaluation of the information and their reasons for participation/non-participation. Odds ratios were calculated and combined in a meta-analysis.
Data from 3/6 SWATs for which it was possible were combined in a meta-analysis (n = 1758). Potential participants allocated to MMI-only were more likely to be recruited to the host trial than those allocated to PIS-only (OR 1.54; 95% CI 1.05, 2.28; p = 0.03). Those allocated to combined MMI + PIS compared to PIS-only were no more likely to be recruited to the host trial (OR = 0.89; 95% CI 0.53, 1.50; p = 0.67). Providing MMI rather than PIS did not impact on DMQ scores. Once children and young people had been recruited to host trials, their trial retention rates did not differ according to intervention allocation.
Providing MMI-only increased the trial recruitment rate compared to PIS-only but did not affect DMQ scores. Combined MMI + PIS instead of PIS had no effect on recruitment or retention. MMIs are a useful tool for trial recruitment in children and young people, and they could reduce trial recruitment periods.
Abstract
OBJECTIVES
Intermittent cold blood cardioplegia is commonly used in children, whereas intermittent warm blood cardioplegia is widely used in adults. We aimed to compare clinical and ...biochemical outcomes with these 2 methods.
METHODS
A single-centre, randomized controlled trial was conducted to compare the effectiveness of warm (≥34°C) versus cold (4–6°C) antegrade cardioplegia in children. The primary outcome was cardiac troponin T over the 1st 48 postoperative hours. Intensive care teams were blinded to group allocation. Outcomes were compared by intention-to-treat using linear mixed-effects, logistic or Cox regression.
RESULTS
97 participants with median age of 1.2 years were randomized (49 to warm, 48 to cold cardioplegia); 59 participants (61%) had a risk-adjusted congenital heart surgery score of 3 or above. There were no deaths and 92 participants were followed to 3-months. Troponin release was similar in both groups geometric mean ratio 1.07; 95% confidence interval (CI) 0.79–1.44; P = 0.66, as were other cardiac function measures (echocardiography, arterial and venous blood gases, vasoactive-inotrope score, arrhythmias). Intensive care stay was on average 14.6 h longer in the warm group (hazard ratio 0.52; 95% CI 0.34–0.79; P = 0.003), with a trend towards longer overall hospital stays (hazard ratio 0.66; 95% CI 0.43–1.02; P = 0.060) compared with the cold group. This could be related to more unplanned reoperations on bypass in the warm group compared to cold group (3 vs 1).
CONCLUSIONS
Warm blood cardioplegia is a safe and reproducible technique but does not provide superior myocardial protection in paediatric heart surgery.
Myocardial protection is typically achieved via cardioplegic arrest.
Abstract
Objective
This study investigated if hybrid oesophagectomy with minimally invasive gastric mobilization and thoracotomy enabled faster recovery than open surgery.
Methods
In eight UK ...centres, this pragmatic RCT recruited patients for oesophagectomy to treat localized cancer. Participants were randomly allocated to hybrid or open surgery, stratified by centre and receipt of neoadjuvant treatment. Large dressings aimed to mask patients to their allocation for six days post-surgery. The authors present the intention-to-treat analysis of outcome measures from the first 3 months post-randomization, including the primary outcome, the patient-reported physical function scale of the EORTC QLQ-C30, and cost-effectiveness. Current Controlled Trials registration: ISRCTN 59036820 (feasibility study), 10386621 (definitive study).
Findings
There was no evidence of a difference between hybrid (n = 267) and open (n = 266) surgery in average physical function over 3 months post-randomization: difference in means 2.1, 95% c.i. −2.0 to 6.2, P = 0.3. Complication rates were similar; for example, 88 (34%) participants in the open and 82 (32%) participants in the hybrid surgery groups experienced a pulmonary infection within 30 days. There was no evidence that hybrid surgery was more cost-effective than open surgery at 3 months.
Conclusions
Patient-reported physical function in the 3 months post-randomization provided no evidence of a difference in recovery time between hybrid and open surgery, or a difference in cost-effectiveness. Both approaches to surgery were completed safely, with a similar risk of key complications, suggesting that surgeons who have a preference for one of the two approaches need not change their practice.
This pragmatic randomized controlled trial conducted in eight UK centres allocated patients with localized oesophageal cancer to hybrid oesophagectomy with minimally invasive gastric mobilization and thoracotomy, or open surgery. The primary outcome was patient-reported recovery in the 3 months following allocation, measured using the EORTC QLQ-C30 physical function subscale. We found no evidence of a difference in recovery time between hybrid and open surgery, and a similar risk of key complications.
IntroductionSurgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an ...oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life.Methods and analysisWe will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery.Ethics and disseminationThis study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal.Trial registration numberISRCTN10386621.
IntroductionPatients with congenital heart disease often need repeated operations throughout life to replace the pulmonary valve. Valve replacement with ‘injectable’ self-expanding valves (which is ...performed ‘off pump’ without the use of cardiopulmonary bypass, CPB) may result in quicker recovery and lower risk of major complications than valve replacement with conventional valves (which is performed ‘on pump’ with the use of CPB).Methods and analysisWe are conducting a multicentre, single-blind randomised controlled trial in patients with congenital heart disease and aged between 12 and 80 years. We will randomise participants in a 1:1 ratio to receive either ‘off pump’ injectable pulmonary valve replacement or ‘on pump’ conventional pulmonary valve replacement. The primary outcome will be the difference between the groups with respect to post-surgery blood loss (as measured by chest drain volume) in the first 24 hours. Secondary outcomes will include in-hospital outcomes (intensive care unit stay, inotropic/vasodilator support, chest drain volume in the first 12 hours post-surgery, time of readiness for extubation, blood products used in the first 24 hours post-surgery, time of fitness for discharge, valve and heart function 6 months post-surgery (assessed using cardiovascular magnetic resonance and ECHOCARDIOGRAPHY) and health-related quality of life 6 weeks and 6 months post-surgery.Ethics and disseminationThis trial has been approved by the South West Exeter Research Ethics Committee. Findings will be shared with participating hospitals and disseminated to the academic community through peer reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and newsletters to participants.Trial registration numberISRCTN23538073
Background:
Digital multimedia information (MMI) has potential for use in trial recruitment but there is little formal evaluation. The objectives were to evaluate digital MMI about a trial for its ...effects on recruitment, retention, participation decisions, and patients' acceptability, compared with printed information (PIS) alone and when combined with PIS.
Methods:
SWAT (study within a trial) using random parallel-group individual allocation within the Thermic-3 trial evaluating warm versus cold cardioplegia solution during cardiac surgery.
Set in one UK hospital, participants were 147 children (0-16 years) awaiting surgery for congenital heart defects; 38% were female.
Participants and their parents/guardian received trial information via multimedia (including text, animated videos and talking-head videos) for viewing at home (MMI group; n=49), or PIS (PIS group; n=47), or both (PIS&MMI group; n=51).
Primary outcome was recruitment rate to the Thermic-3 trial comparing PIS-alone and MMI-alone. Secondary outcomes were recruitment rate comparing PIS-alone and combined PIS Decision-Making Questionnaire; 3 'free-text' questions (deriving subjective evaluations); trial retention.
Results:
MMI produced a 14.2% absolute increase in recruitment, which was not statistically significant: 32 (65.3%) participants were recruited from the MMI group; 24 (51.1%) from the PIS group (OR 1.80; 95% CI 0.79 to 4.10, p = 0.16); and 22 from the PIS&MMI group. There was no difference in recruitment through combined PIS&MMI (43.1% vs 51.1%; OR 0.73; 95% CI 0.33 to 1.61; p= 0.43). Questionnaires were returned by 17 (12%) participants and analysed descriptively. Trial retention (at 3 months) was high in all groups (72/77; 93.5% overall) and there was no difference due to information format received before participating.
Conclusions:
MMI increased recruitment to the Thermic-3 trial but the difference was not statistically significant, and the SWAT was small.
Trial registration: TRECA
ISRCTN73136092 and NI Hub for Trials Methodology Research SWAT Repository (SWAT 97). Thermic-3:
ISRCTN13467772.
IntroductionSurgical repair of congenital heart defects often requires the use of cardiopulmonary bypass (CPB) and cardioplegic arrest. Cardioplegia is used during cardiac surgery requiring CPB to ...keep the heart still and to reduce myocardial damage as a result of ischaemia–reperfusion injury. Cold cardioplegia is the prevalent method of myocardial protection in paediatric patients; however, warm cardioplegia is used as part of usual care throughout the UK in adults. We aim to provide evidence to support the use of warm versus cold blood cardioplegia on clinical and biochemical outcomes during and after paediatric congenital heart surgery.Methods and analysisWe are conducting a single-centre randomised controlled trial in paediatric patients undergoing operations requiring CPB and cardioplegic arrest at the Bristol Royal Hospital for Children. We will randomise participants in a 1:1 ratio to receive either ‘cold-blood cardioplegia’ or ‘warm-blood cardioplegia’. The primary outcome will be the difference between groups with respect to Troponin T levels over the first 48 postoperative hours. Secondary outcomes will include measures of cardiac function; renal function; cerebral function; arrythmias during and postoperative hours; postoperative blood loss in the first 12 hours; vasoactive-inotrope score in the first 48 hours; intubation time; chest and wound infections; time from return from theatre until fit for discharge; length of postoperative hospital stay; all-cause mortality to 3 months postoperative; myocardial injury at the molecular and cellular level.Ethics and disseminationThis trial has been approved by the London – Central Research Ethics Committee. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and newsletters to participants.Trial registration numberISRCTN13467772; Pre-results.
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