GRACE: Evaluating Compression Stockings in Patients That Require Extended Duration Pharmacological Thromboprophylaxis

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:-

• patients undergoing surgical procedures requiring EDPTP benefit from additional GCS to prevent VTE
• patients receiving GCS experience an increased rate of adverse events

Methods: Assessor-blinded randomised controlled trial with a non-inferiority comparison. 8,608 participants will be randomised in a 1:1 fashion to one of two thromboprophylaxis strategies:

• EDPTP* in addition to GCS, or
• 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.

Everyone in the study will get an ultrasound scan at 21 - 35 days after their operation to check if they have developed a blood clot. This is an additional scan, not routinely performed in the NHS, to make sure that all blood clots are detected at an early stage. Participants will receive a phone call at 7, 21-35 and 90 days after their treatment to see if they have developed a blood clot or had any problems with the treatment.

Inclusion criteria

• Adults (≥18 years of age)
• Participants undergoing elective surgery; risk assessed as requiring EDPTP

Exclusion criteria

• Contraindications to EDPTP or GCS
• Individuals requiring therapeutic anticoagulation e.g., anticoagulation for previous DVT
• Known thrombophilia or thrombogenic disorder