Post-Operative Prevention of Venous Thromboembolism in Hip and Knee Arthroplasty Surgery: A Study of the Combined Use of Low Molecular Weight Heparin and Rivaroxaban

IntroductionVenous 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 analysisThis 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 disseminationEthics 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.

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Role of Low Molecular Weight Heparin in Thromboprophylaxis for Hip and Knee Arthroplasty

Indian Journal of Public Health Research & Development ◽

10.5958/0976-5506.2019.00685.5 ◽

2019 ◽

Vol 10 (4) ◽

pp. 174

Author(s):

Deepinder Chaudhary ◽

Mahipat Singh ◽

Manrattan Bhathal ◽

Neha Baiswar ◽

Jayant Randhawa ◽

...

Keyword(s):

Molecular Weight ◽

Knee Arthroplasty ◽

Low Molecular Weight Heparin ◽

Low Molecular Weight ◽

Hip And Knee Arthroplasty

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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): statistical analysis plan

Trials ◽

10.1186/s13063-021-05486-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Verinder Singh Sidhu ◽

Thu-Lan Kelly ◽

Nicole Pratt ◽

Steven Graves ◽

Rachelle Buchbinder ◽

...

Keyword(s):

Molecular Weight ◽

Statistical Analysis ◽

Venous Thromboembolism ◽

Knee Arthroplasty ◽

Low Molecular Weight Heparin ◽

Statistical Analysis Plan ◽

Low Molecular Weight ◽

Thromboembolism Prophylaxis ◽

Cluster Randomised ◽

Secondary Outcomes

Abstract 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.

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