CRISTAL: Cluster Randomised Trial of Apsirin versus Low molecular weight heparin for venous thromboembolism

Hip and knee replacement surgery represent the two most costly medical procedures performed in Australia (over $2 billion in direct costs annually). Venous thromboembolism is an uncommon but serious complication of joint replacement surgery and although chemoprophylaxis is routinely recommended, there is uncertainty and controversy regarding which drugs should be used. Low molecular weight heparin (LMWH) given by injection for several weeks is most
commonly recommended and used but many surgeons use aspirin as standalone chemoprophylaxis as it is a low cost, safe, and easy to use alternative that is
preferred by patients. Systematic reviews have highlighted the lack of high quality evidence and the need for large high quality trials comparing aspirin to
other drugs. The population under study is people undergoing elective hip or knee replacement at hospitals contributing to the National Joint Replacement Registry (NJRR) PROMs (patient reported outcome measures) program. The intervention is aspirin given orally (daily) for 28-35 days post-operatively. The
comparator is LMWH injections (daily) for 28-35 days post-operatively. The primary outcome is image-confirmed symptomatic venous thromboembolism
(DVT or PE) within 90 days. This study will use the NJRR PROMs program to perform a nested, cluster randomised crossover trial. This design will embed the trial as standard practice at each site resulting in high compliance and generalisability, and will allow a large sample size to be collected over a relatively short time. The crossover design, where each site (cluster) contributes to both arms of the study, will reduce confounding from between-site variation.
By developing the study simultaneously with the PROMs program, the study will lay the groundwork (experience and software) for future large efficient
registry-nested trials within the NJRR. The trial will address practice variation and lead to uniform best practice in VTE prevention for these common procedures.