CRISTAL: protocol for a cluster randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study
Rachelle Buchbinder,
Ornella Clavisi,
Ian A Harris,
Nicole L Pratt,
Steve Webb,
Richard S de Steiger,
Sam Adie,
Verinder Singh Sidhu,
Steven E Graves,
Justine Maree Naylor,
Beng H Chong,
Ilana N Ackerman,
Anthony Harris,
Amber Hansen,
Maggie Cripps,
Michelle Lorimer,
Elizabeth C Griffith,
Durga Anandan,
Grace O'Donohue,
Thu-Lan Kelly
Affiliations
Rachelle Buchbinder
Musculoskeletal Health and Wiser Health Care Units, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
Ornella Clavisi
Musculoskeletal Australia, Melbourne, Victoria, Australia
Ian A Harris
Sydney Musculoskeletal Health, Institute for Musculoskeletal Health, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney and Sydney Local Health District, Sydney, NSW, Australia
Nicole L Pratt
Quality Use of Medicines and Pharmacy Research Centre, University of South Australia Clinical & Health Sciences Academic Unit, Adelaide, South Australia, Australia
Steve Webb
Department of Intensive Care, St John of God Hospital, Subiaco, Western Australia, Australia
Richard S de Steiger
Australian Orthopaedic Association National Joint Replacement Registry, Adelaide, South Australia, Australia
Sam Adie
St George and Sutherland Clinical Campuses, School of Clinical Medicine, UNSW Medicine & Health, Sydney, New South Wales, Australia
Verinder Singh Sidhu
CRISTAL Study Group, Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, University of New South Wales South Western Sydney Clinical School, Liverpool, New South Wales, Australia
Steven E Graves
Australian Orthopaedic Association National Joint Replacement Registry, Adelaide, South Australia, Australia
Justine Maree Naylor
CRISTAL Study Group, Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, University of New South Wales South Western Sydney Clinical School, Liverpool, New South Wales, Australia
Beng H Chong
Department of Haematology, Saint George and Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
Ilana N Ackerman
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
Anthony Harris
Centre for Health Economics, Monash University, Melbourne, Victoria, Australia
Amber Hansen
CRISTAL Study Group, Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, University of New South Wales South Western Sydney Clinical School, Liverpool, New South Wales, Australia
Maggie Cripps
CRISTAL Study Group, Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, University of New South Wales South Western Sydney Clinical School, Liverpool, New South Wales, Australia
Michelle Lorimer
Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), Adelaide, Australia
Elizabeth C Griffith
South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
Durga Anandan
Australian Orthopaedic Association National Joint Replacement Registry, Adelaide, South Australia, Australia
Grace O'Donohue
Australian Orthopaedic Association National Joint Replacement Registry, Adelaide, South Australia, Australia
Thu-Lan Kelly
Clinical and Health Sciences Academic Unit, University of South Australia, Adelaide, South Australia, Australia
Introduction Venous thromboembolism (VTE) is a serious complication following hip arthroplasty (HA) and knee arthroplasty (KA). This study aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic VTE following HA and KA.Methods and analysis This is a cluster randomised, crossover, non-inferiority, trial nested within the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). The clusters will consist of Australian hospitals performing at least 250 HA and/or KA procedures per annum. All adult patients undergoing HA or KA will be included. The intervention will be aspirin, orally, 85–150 mg daily. The comparator will be LMWH (enoxaparin) 40 mg, subcutaneously, daily. Both drugs will commence within 24 hours postoperatively and continue for 35 days after HA and 14 days after KA. Each hospital will be randomised to commence with aspirin or LMWH and then crossover to the alternative treatment after meeting the recruitment target. Data will be collected through the AOANJRR via patient-reported surveys. The primary outcome is symptomatic VTE within 90 days post surgery, verified by AOANJRR staff. The primary analysis will include only patients undergoing elective primary total hip arthroplasty and total knee arthroplasty for osteoarthritis. Secondary outcomes will include symptomatic VTE for all HA and KA (including partial and revision) within 90 days, readmission, reoperation, major bleeding and death within 90 days and reoperation, death and patient-reported pain, function and health status at 6 months. If aspirin is found to be inferior, a cost-effectiveness analysis will be conducted. The study will aim to recruit 15 562 patients from 31 hospitals.Ethics and dissemination Ethics approval has been granted. Trial results will be submitted for publication. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001879257, pre-results) and is endorsed by the Australia and New Zealand Musculoskeletal Clinical Trials Network.
