GRACE: protocol for a UK, secondary care, multicentre, assessor-blinded randomised controlled trial with a non-inferiority comparison to evaluate graduated compression stockings as an adjunct to extended duration pharmacological thromboprophylaxis for venous thromboembolism prevention

Abstract

Introduction: Venous thromboembolism (VTE) occurs when a blood clot forms in a vein. It is comprised of deep vein thrombosis (DVT) and pulmonary embolism and can be potentially life-threatening. Patients undergoing surgery are at increased risk of developing VTE within hospital admission and 90 days after hospital discharge are collectively known as hospital-acquired thrombosis (HAT). Without the use of thromboprophylaxis, the untreated risk of VTE is reported to be as high as 40-60% in those undergoing major orthopaedic procedures and around 15-40% in the general surgical population.HAT accounts for around 12 000 deaths per year in the UK. For patients undergoing surgery, there is good evidence for the use of thromboprophylaxis to prevent VTE.Thromboprophylaxis is available in both pharmacological and mechanical forms. While there is a huge body of evidence demonstrating that pharmacological thromboprophylaxis significantly reduces VTE by 30-65%, the benefit of graduated compression stockings (GCS) has been called into question. The GRACE study (Graduated Compression stocking as an adjunct to Extended duration pharmacological thromboprophylaxis for venous thromboembolism prevention) aims to evaluate the adjuvant benefit of GCS in addition to extended duration pharmacological thromboprophylaxis (EDPTP) for elective surgical patients at highest risk of VTE.

Methods and analysis: GRACE is a pragmatic, multicentre randomised trial of adults undergoing surgery who are at high risk of VTE. Participants are randomised into a 1:1 ratio to either EDPTP and compression stockings (control arm) or EDPTP (intervention arm). Following randomisation, participants will undergo surgery and be followed up centrally at 7, 21-35 and 90 days after their procedure. All participants will be offered a bilateral full lower limb duplex scan at 21-35 days post procedure to capture any asymptomatic DVT.The trial aims to randomise 8608 participants from around 50 National Health Service (NHS) and non-NHS sites in the UK over a 24-month period. The primary endpoint is any imaging-confirmed incidence of VTE within 90 days of surgery.

Ethics and dissemination: On 20 December 2023, GRACE received favourable ethical approval from the Wales Research Ethics Committee 3 Cardiff (23/WA/0350) and the Health Research Authority (IRAS 333539). The results of the study will be disseminated via peer-reviewed publications, presentation at national and international conferences and to study participants via electronic newsletter and social media channels.

Trial registration number: ISRCTN11667770.

Keywords: HAEMATOLOGY; SURGERY; Thromboembolism.

Figure 1. The Consolidated Standards of Reporting Trials flow diagram of the GRACE trial population. DVT, deep vein thrombosis; GCS, graduated compression stockings; GRACE, Graduated Compression stocking as an adjunct to Extended duration pharmacological thromboprophylaxis for venous thromboembolism prevention; VTE, venous thromboembolism.