Hancock 2019.

Study characteristics
Methods	Study design: single‐centre, single‐blind, prospective, randomised, controlled superiority trial Duration: 28 months No. of centres: single Location: UK Setting: university hospital Withdrawals: 1 (randomised in error and did not receive any surgery) Dates: March 2014 to July 2016
Participants	270 participants scheduled for elective, isolated aortic valve replacement Exclusion criteria: concomitant cardiac procedures, redo surgery, only suitable for median sternotomy, haemoglobin < 90g/L, pregnant, in another interventional trial, previous cardiac surgery, unable to stop anticoagulant treatment, history of thrombophilia, thrombocytopaenia, or other haematological conditions that would affect participation (as assessed by any of the participating surgeons), infective endocarditis, prevented from having blood products according to a system of beliefs, any other medical, psychiatric or social reason to preclude participation Demographics[limited / full sternotomy] Number of participants: 270 [135 / 135] Mean age (± SD): [69.3 ± 9.3 years / 68.7 ± 8.4 years] Male gender: [78 (58%) / 87 (64%)] Pathophysiology (AS:AR:mixed): [(132:3:0) / (127:8:0)] Severity of disease mean gradient: not stated Mean risk score: EuroSCORE II [1.5 ± 1.1 / 1.5 ± 1.2] and Logistic EuroSCORE I [5.2 ± 3.5 / 5.1 ± 3.5] Diabetes mellitus: not stated Preoperative FEV1: [2.1 ± 0.7 / 2.2 ± 0.7] Preoperative FVC: [2.9 ± 0.9 / 2.9 ± 1.0] Smoking status: not stated
Interventions	Limited sternotomy: limited median skin incision (5 to 7 cm) and manubrium‐limited mini‐sternotomy to 1 cm below manubrio‐sternal junction. Modifications from full sternotomy: percutaneous femoral venous cannulation instead of 2‐stage right atrio‐caval cannula
Outcomes	Primary outcome Proportion of patients receiving a red cell transfusion postoperatively and within 7 days of aortic valve replacement surgery Secondary outcomes Proportion of patients receiving a red cell transfusion and the number of units transfused within 7 days of index surgery and during the index hospital stay Proportion of patients receiving a non‐red cell blood component transfusion and the number of units transfused within 7 days of index surgery and during the index hospital stay Volume in chest drains at 6 and 12 hours, and at drain removal Changes in Hb from baseline to 4 days following index surgery Operative success (degree of aortic regurgitation) assessed using echocardiogram within 6 weeks following index surgery Re‐operation rates Conversion to conventional AVR during index surgery Changes in lung function at 4 days and 6 weeks following index surgery Quality of life EuroQol (EQ‐5D‐3L, EQ‐VAS) at day 2, 6 weeks and 12 weeks following index surgery Time until which patients are deemed ‘fit for discharge’ Health care utilisation to 12 weeks Cost and cost‐effectiveness analyses Adverse events to 12 weeks following index surgery
Standard care	Patients are given lorazepam as a pre‐medication, followed by anaesthesia with propofol, fentanyl, rocuronium bromide and morphine. All patients are given a total dose of tranexamic acid (TXA) at 30 mg/kg. Where patients have a presurgical creatinine >200 mmol/L, the dose of TXA is halved to 15 mg/kg. Prior to cardiopulmonary bypass, systemic anticoagulation is achieved with heparin given at a dose that achieves an activated clotting time (ACT) of greater than 400 seconds. Fresh frozen plasma (FFP) is administered if the target ACT is not reached. During cardiopulmonary bypass, haemoglobin (Hb) is kept at 60 g/L or above. Haemofiltration followed by RBC transfusion may be required to achieve this. Following cardiopulmonary bypass (CPB), protamine administered to reverse heparin, according to the dose of heparin given. Blood products may be used intra‐operatively in the presence of excessive blood loss. Cell salvage will be used in all patients All patients have the new aortic valve assessed at the end of surgery using a transoesophageal echocardiogram (TOE)
Notes	16 patients crossed over from limited sternotomy to conventional median sternotomy. Data analysed as intention‐to‐treat Funded by National Institute for Health and Care Research (NIHR) (United Kingdom). 1 author declared competing interests with funding from the British Heart Foundation and NIHR, and grant funding from Zimmer Biomet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised by designated and trained members of the research team using a 24‐hour, central, secure, web‐based randomization system with concealed allocation, managed by Durham Clinical Trials Unit. Eligible patients were randomised in a 1:1 ratio between the intervention under study and usual care. Randomisation stratified by baseline logistic EuroSCORE and preoperative Haemoglobin (Hb).
Allocation concealment (selection bias)	Low risk	Web‐based randomisation with concealed allocation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All patients were blinded to the type of sternotomy they received until after they completed their day 2 quality of life and pain assessments. All patients had trial‐specific opaque dressings applied to their sternal wound, and to their groin. Clinical teams were informed of surgical allocation.
Blinding of outcome assessment (detection bias) Low risk from non‐blinding (objective measures)	Low risk	Blinding used for some outcomes up to 2 days
Blinding of outcome assessment (detection bias) At risk from non‐blinding (subjective measures)	Low risk	Other outcomes unlikely to be influenced by blinding (e.g. bleeding)
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomised participants reported
Selective reporting (reporting bias)	Low risk	All relevant outcomes reported
Other bias	Low risk	No other risks identified