News

The CRISTAL Trial - A/Prof. Sam Adie

Sep 27, 2022

The CRISTAL trial1 was recently published in August 2022, comparing two commonly used thromboprophylaxis agents (aspirin vs. enoxaparin) to prevent symptomatic venous thromboembolism within 90 days of primary total hip and knee replacement.

The trial found that enoxaparin was superior to aspirin, with an absolute reduction of just under 2% in symptomatic venous thromboembolism (95% confidence interval 0.54% - 3.41%). The results were similar when different subgroups were examined - knees vs. hips, unilateral vs. bilateral, but there appeared to be a larger benefit to using enoxaparin in those with a history of thromboembolism. Although designed to be a non-inferiority trial, the trial was actually stopped early when aspirin (blinded at the time) was found to be clearly superior by our data safety monitoring committee.

CRISTAL is superlative in many ways. Firstly, it provides accurate information on a clinical controversy that has persisted for decades. But it also represents the best of Australian scientific collaboration. With just under 10,000 patients and 31 centres involved, it is easily the largest orthopaedic trial ever conducted. It received ~$1million in funding from the NHMRC Medical Research Future Fund. CRISTAL also exhibits an innovative, efficient research design, where centres were cluster randomised, and data was nested and managed by the AOA National Joint Replacement Registry. For comparison, similar sized “traditional” trials with individual randomisation would easily cost several million dollars. No surprise then that several orthopaedic trials are in the pipeline that are using a similar efficient design. Ramsay hospitals were strongly represented, and St. George Private was one of the largest contributors of patients to the trial, a testament to the dedication of the entire team to patient care and scientific advancement.

CRISTAL was published in JAMA- one of the world’s top journals – with evidence of an immediate global impact and media interest. It was a true privilege to be involved with the core team of the CRISTAL trial- but true credit goes to Professor Ian Harris and our PhD student Dr. Verinder “Vinny” Sidhu who led CRISTAL to it’s well-deserved success.

A/Prof. Sam Adie
BSc(Med) MBBS(Hons) MSpMed MPH PhD FRACS(Ortho) FAOA
Conjoint Associate Professor - Orthopaedic Surgeon
School of Clinical Medicine, UNSW Medicine & Health

Level 2, Suite 201

St George Private Specialist Consulting Suites, 131 Princes Highway (Access via South Street)

Kogarah, NSW, 2217

Ph: 02 9587 4720

Fax: 02 9587 6927 

Reference

1. CRISTAL Study Group. Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial. JAMA. 2022;328(8):719–727.