TY - JOUR
T1 - CRISTAL (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)
T2 - statistical analysis plan
AU - Sidhu, Verinder Singh
AU - Kelly, Thu Lan
AU - Pratt, Nicole
AU - Graves, Steven
AU - Buchbinder, Rachelle
AU - Naylor, Justine
AU - de Steiger, Richard
AU - Ackerman, Ilana
AU - Adie, Sam
AU - Lorimer, Michelle
AU - Bastiras, Durga
AU - Cashman, Kara
AU - Harris, Ian
N1 - Funding Information:
The study is being funded by a four-year Medical Research Futures Fund (MRFF – Australian Federal Government) grant. The funding was not provided with any conditions and the MRFF has no authority over the design of the study or collection, management, analysis or interpretation of data or the writing of manuscripts for submission. No industry funding or other sources of funding are being used for this trial.
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/24
Y1 - 2021/8/24
N2 - Background: This a priori statistical analysis plan describes the analysis for CRISTAL. Methods: CRISTAL (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) aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic venous thromboembolism (VTE) following hip arthroplasty (HA) or knee arthroplasty (KA). The study is nested within the Australian Orthopaedic Association National Joint Replacement Registry. The trial was commenced in April 2019 and after an unplanned interim analysis, recruitment was stopped (December 2020), as the stopping rule was met for the primary outcome. The clusters comprised hospitals performing > 250 HA and/or KA procedures per annum, whereby all adults (> 18 years) undergoing HA or KA were recruited. Each hospital was randomised to commence with aspirin, orally, 85–150 mg daily or LMWH (enoxaparin), 40 mg, subcutaneously, daily within 24 h postoperatively, for 35 days after HA and 14 days after KA. Crossover was planned once the registration target was met for the first arm. The primary end point is symptomatic VTE within 90 days. Secondary outcomes include readmission, reoperation, major bleeding and death within 90 days, and reoperation and patient-reported pain, function and health status at 6 months. The main analyses will focus on the primary and secondary outcomes for patients undergoing elective primary total HA and KA for osteoarthritis. The analysis will use an intention-to-treat approach with cluster summary methods to compare treatment arms. As the trial stopped early, analyses will account for incomplete cluster crossover and unequal cluster sizes. Conclusions: This paper provides a detailed statistical analysis plan for CRISTAL. Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12618001879257. Registered on 19/11/2018.
AB - Background: This a priori statistical analysis plan describes the analysis for CRISTAL. Methods: CRISTAL (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) aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic venous thromboembolism (VTE) following hip arthroplasty (HA) or knee arthroplasty (KA). The study is nested within the Australian Orthopaedic Association National Joint Replacement Registry. The trial was commenced in April 2019 and after an unplanned interim analysis, recruitment was stopped (December 2020), as the stopping rule was met for the primary outcome. The clusters comprised hospitals performing > 250 HA and/or KA procedures per annum, whereby all adults (> 18 years) undergoing HA or KA were recruited. Each hospital was randomised to commence with aspirin, orally, 85–150 mg daily or LMWH (enoxaparin), 40 mg, subcutaneously, daily within 24 h postoperatively, for 35 days after HA and 14 days after KA. Crossover was planned once the registration target was met for the first arm. The primary end point is symptomatic VTE within 90 days. Secondary outcomes include readmission, reoperation, major bleeding and death within 90 days, and reoperation and patient-reported pain, function and health status at 6 months. The main analyses will focus on the primary and secondary outcomes for patients undergoing elective primary total HA and KA for osteoarthritis. The analysis will use an intention-to-treat approach with cluster summary methods to compare treatment arms. As the trial stopped early, analyses will account for incomplete cluster crossover and unequal cluster sizes. Conclusions: This paper provides a detailed statistical analysis plan for CRISTAL. Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12618001879257. Registered on 19/11/2018.
KW - Aspirin
KW - Hip arthroplasty
KW - Knee arthroplasty
KW - Low molecular weight heparin
KW - Statistical analysis plan
KW - Venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=85113811216&partnerID=8YFLogxK
U2 - 10.1186/s13063-021-05486-0
DO - 10.1186/s13063-021-05486-0
M3 - Article
C2 - 34429127
AN - SCOPUS:85113811216
SN - 1745-6215
VL - 22
JO - Trials
JF - Trials
IS - 1
M1 - 564
ER -