Inpatient GRAduated Compression stocking use as an adjunct to Extended duration pharmacoprophylaxis for venous thromboembolism prevention – the GRACE multi-centre randomised controlled trial

Research question: Is it beneficial to provide graduated compression stockings (GCS) in addition to extended duration pharmacological thromboprophylaxis (EDPTP) for surgical patients at highest risk of venous thromboembolism (VTE)? Background: Hospital-acquired thrombosis (HAT) is defined as any VTE within 90 days of hospital admission, encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE). HAT represents a significant cause of preventable mortality, with over 12,000 people dying each year from hospital-associated VTE in the UK, 10-fold higher than the number dying from road traffic accidents. Previous studies report that the risk of untreated high-risk surgical patients developing HAT is as high as 40-60% in orthopaedic patients and 15-40% in general surgery patients. For these patients at highest risk of VTE, key prevention strategies include extended pharmacological thromboprophylaxis (EDPTP) prescribed beyond hospital discharge and provision of graduated compression stockings (GCS). There is compelling evidence to support the use of pharmacological thromboprophylaxis, however, there is little evidence to support the use of additional GCS alongside causing complications in as many as 5% of patients. The cost of providing GCS equates to a minimum of £31.05 per patient episode, with as many as 270,000 relevant procedures conferring a high-risk of VTE, it could be costing the NHS £8.3 million per annum. Aims and objectives: The GRACE trial aims to establish whether:- 1. patients undergoing surgical procedures requiring EDPTP benefit from additional GCS to prevent VTE 2. patients receiving GCS experience an increased rate of adverse events Methods: Assessor-blinded randomised controlled trial with a non-inferiority comparison using an intention-to-treat analysis. 8,554 participants will be randomised in a 1:1 fashion to one of two thromboprophylaxis strategies: 1. EDPTP* in addition to GCS, or 2. EDPTP alone *EDPTP includes any anti-thrombotic agent prescribed at a prophylactic dose for prevention of VTE, including low-molecular weight heparin, directly acting oral anticoagulants, or antiplatelet therapy. Included participants will be those undergoing surgical intervention who are deemed to require extended duration thromboprophylaxis. Exclusion criteria includes those with a known thrombophilia, prescribed therapeutic anticoagulation or have a contraindication to EDTPT or GCS. Primary outcome is imaging confirmed lower limb DVT with or without symptoms, or PE with symptoms <90 days from treatment. Timelines for delivery: 39-month study duration – 6m set-up, 24m recruitment, 3m follow-up, 6m close-down. Anticipated impact and dissemination: Findings will guide international clinical practice and stimulate updates to international guidelines, including NICE [NG89]. Results will be published in high-impact journals alongside presentation at international surgery and haematology societies. This trial is supported by organisations who will play a key role in dissemination: Association of Surgeons of Great Britain & Ireland, British Association of Urological Surgeons, British Orthopaedic Association, British Society for Haematology, British Urology Researchers in Surgical Training, Circulation Foundation, UK Perioperative Medicine Clinical Trials Network, Royal College of Surgeons, Royal Society of Medicine, Thrombosis UK, Vascular All Party Parliamentary Group, Vascular Society, VERN, Venous SIG and the Venous Forum.