Compression Hosiery to Avoid the Post-Thrombotic Syndrome: a synopsis of the CHAPS RCT.

Background: Approximately half of adults diagnosed with deep vein thrombosis will develop the post-thrombotic syndrome leading to chronic symptoms - including leg pain, oedema, venous ectasia and, in 5% of cases, venous ulceration. Risk factors include older age, obesity, a history of blood clots, cancer and heart failure. Despite adequate anticoagulation, post-thrombotic syndrome remains a chronic health condition with significant financial burden for patients and health services. The effectiveness of compression stockings in preventing post-thrombotic syndrome is unclear and whether the risks and costs associated with compression stockings are justified. Design: The Compression Hosiery to Avoid Post-Thrombotic Syndrome study was a multicentre, pragmatic, assessor-blind, randomised controlled trial of adults with a first proximal deep vein thrombosis. Setting: Secondary care National Health Service hospitals in the United Kingdom. Participants: Patients ≥ 18 years, with imaging-confirmed, symptomatic presentation of first deep vein thrombosis in the lower limb (popliteal, femoral, iliac or combination), ≤ 3 weeks from diagnosis. Interventions: Participants were randomised 1 : 1 to standard care (anticoagulation as per local guidelines) or intervention (anticoagulation as per local guidelines and regular use of a graduated compression stocking). Primary outcome: The primary outcome was any incidence of post-thrombotic syndrome using the Villalta criteria over a median of 18-month follow-up (range 6-30 months). This was planned to be assessed on up to three occasions (6 and 12 months post randomisation and at study end), depending on when an individual was randomised. Secondary outcomes: Planned secondary outcomes: incidence of venous ulceration (measured by the validated Villalta criteria) employment status (change in the number of days working from baseline) change in disease-specific and generic quality of life - Venous Insufficiency Epidemiological and Economic Study (VEINES-QOL/Sym) and EuroQol-5 Dimensions scales from baseline over 6 months, 12 months and end of study visit adherence to stockings and anticoagulants (patient self-report) cost-effectiveness of stocking prescription - incremental cost-effectiveness ratio from the EuroQol-5 Dimensions questionnaire, with appropriate sensitivity analysis. Results: The trial closed early due to poor recruitment during the COVID-19 pandemic; and, of the planned sample size of 864, 152 participants were randomised. Post-thrombotic syndrome occurred in 51% of the control arm and in 30% of the intervention arm at last follow-up. No serious adverse events relating to stockings were recorded. Stocking adherence was a mean of 6 days (standard deviation 2) per week. Conclusions: The sample size was not reached, which precluded any formal statistical analysis. Although a difference in the incidence of post-thrombotic syndrome was demonstrated, the effect size could not be determined. There is interest in understanding optimal strategies for the prevention of post-thrombotic syndrome in these patients and a re-run of this trial should occur. Limitations: The main limitation was its early termination. As a result, it did not reach the required sample size to draw any adequately powered conclusions. The analyses are descriptive and therefore we cannot determine whether there were any differences between trial arms. Future work: Answering the question of whether graduated compression stockings help prevent the post-thrombotic syndrome is important to both patients and clinicians. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/147/47.