Title: Minimally invasive thoracoscopically-guided right minithoracotomy versus conventional sternotomy for mitral valve repair: a multicentre randomised controlled trial (UK Mini Mitral)
Funder: Department of Health and Social Care

Abstract: Design: multi-centre, randomised controlled trial including an internal pilot. Setting: UK cardiac surgery units. Literature review: Cochrane, PubMed, ISRCTN, clinicaltrials.gov had no relevant trials. Population: Adults with degenerative mitral valve disease requiring isolated Mitral Valve repair (MVr), able to provide written informed consent, fit for surgery. Exclusions: concomitant surgery (except patent foramen ovale or atrial fibrillation), acute infective endocarditis, redo surgery, emergency or salvage surgery. Health Technology: MVr via thoracoscopically-guided right minithoracotomy. Comparator: MVr via median sternotomy. Measurement of costs and outcomes: Primary outcome: return to usual activity using change in SF-36v2 physical functioning scale (1) at 12 weeks. Primary economic outcome: cost/QALY gained after one year of treatment. Secondary outcomes include: cardiac function assessed echocardiographically (by central blinded assessor) post-operatively and at 52 weeks; operative results, peri-operative complications, length of hospital stay, NYHA class (5); resource use, mortality and mitral valve related events; physical function (SF-36v2(1)), level of physical activity, quality of sleep (accelerometer (6-10)), quality of life, (SF-36v2 & ED-5D-5L (1,2-4)). Patients will consent to follow-up beyond 12 months using hospital episode statistics (HES), informing clinical and economic models extrapolating outcomes to 4.5 years. Primary analysis of change in SF-36v2 at 12 weeks using intention to treat principles will use a general linear model accounting for intervention, baseline scores, valve pathology and concomitant surgery. Secondary analysis will be: continuous outcomes by general linear model, binary outcomes by generalised estimating equation, time to event outcomes by log-rank test and frailty modelling. Analysis of repeated measures will account for intra-patient correlation. Hierarchical modelling of patients, surgeons and centres, will provide an estimate of treatment effect. Base case economic evaluation will estimate the effect of surgery using bootstrapped, bivariate regression modelling of costs and QALYs adjusted as per the primary analysis. Multiple imputation will sensitise incomplete data. All outcomes will also be analysed using simple statistics. Sample size: Assuming alpha of 5% and 90% power, 382 patients are required to detect a minimally clinically important difference of 10 points in the SF-36v2(1) physical functioning scale at 12 weeks (assuming a SD of 30 (11)). Patients will be recruited from 4 sites to enable recruitment to target. Allowing for attrition, 400 patients will be randomised. Timetable: Prior to grant: 6 months set-up; protocol and study material development, ethics and governance, trial database. Data access contracts. 0-6 months: internal pilot, recruitment, surgery, assessments at 4 centres. Performance against stopping guidelines evaluated. 7-55 months: recruitment, surgery, trial assessments and follow-up using HES data, validated with data from the National Institute for Cardiovascular Research (NICOR) and medical records by an expert panel. 55-60 months: final expert panel, final data cleaning, analysis, report writing, dissemination, consultation on further collection of follow-up data. Expertise: a track record of working together on successful nationally-funded cardiac surgery trials; together we have key clinical, academic and trials expertise.

Lay abstract: Heart surgery to repair one of the valves in the heart (the mitral valve) is commonly performed in the NHS. Patients needing this operation sometimes suffer symptoms of shortness of breath (especially when exercising), tiredness, and swollen ankles, caused by the valve becoming leaky (mitral regurgitation). Some patients suffer very few symptoms. These patients are quite often of working age so time away from their place of work can be difficult for a number of reasons. We need to make sure that the operations offered within the NHS are best for patients. To repair the valve, the operation usually involves cutting the breastbone completely (from the collar bone to the bottom of the breastbone); this is called a sternotomy. An operation has been developed which means that the valve can be repaired using a much smaller cut on the side of the chest; this operation is called a mini-thoracotomy. The trouble is, we don’t know which operation is better for patients and for the NHS because there is no good research to show what effects two different types of surgery to access the heart and repair the valve have on patients. We have spoken to heart doctors and heart surgeons in the UK and the USA as well as to patients who have had each of these types of surgery, and to patients waiting for surgery. They all think it is important that we know which operation enables patients to return to normal activities sooner after the operation on their mitral valve. This study will compare the two operations in four hundred adult patients, to see how well they recover and return to normal activities. The trial will include patients at four NHS hospitals in England. Patients will be randomised (allocated) to undergo one of the operations. The trial is large enough to show which operation is better for patients and the NHS. We will ask patients who take part questions about their physical activities and quality of life before and after their operation. We will also check other important factors to see how well patients recover, including how well their valve works up to twelve weeks and twelve months after surgery using a heart scan (called an echocardiogram). We will ask patients to wear a device that measures their activity for one week on seven occasions; the device looks like a wrist-watch and can be worn all day and all night. Any complications following a patient’s operation will be recorded from their medical records. We will also calculate the costs of care for each operation by looking at medical records to see how often patients are seen in hospital after their operation. Patients who take part will attend hospital a few times in the first year, after this we will continue to check their progress by reviewing their medical notes. We will ask patients to confirm that they are happy that we keep looking at their medical records, even after the trial is finished.

Research activity codes: 6.4 SURGERY
Health categories: CARDIOVASCULAR