Title: CHAPS: Compression Hosiery to Avoid Post-Thrombotic Syndrome
Funder: Department of Health and Social Care

Abstract: Every year 1 in 1000 persons in the UK are diagnosed with a blood clot in the leg veins (deep vein thrombosis). In just under half of those with deep vein thrombosis, leg pain, swelling and skin breakdown (ulcers) can occur, a lifelong condition called post-thrombotic syndrome. This impacts upon a person’s ability to work, their confidence and independence. In most patients there is no effective treatment and they lose income from unemployment. Ulcers, if they occur, require bandaging that needs to be changed twice weekly._x000D_ _x000D_ Treatment guidelines for deep vein thrombosis do not currently include the use of a compression stockings. They can sometimes be difficult to put on for those who cannot bend down, the stockings can slip or roll down, or become uncomfortable in hot weather. Stockings cost the NHS approximately £50 every 6 months._x000D_ _x000D_ The evidence for stockings comes from two early trials comparing patients wearing a stocking to those who did not. There was a large benefit in both these trials for wearing a stocking, with no major side effects. In 2014, a Canadian group published a trial comparing wearing a compression stocking to wearing a non-compressive stocking. The rates of post-thrombotic syndrome were identical. The Canadian trial also suggested that only half of patients actually wear stockings, one reason the trial may have shown no difference. The Canadian trial suggested that stockings did not prevent future thrombosis or help leg pain. Whilst UK NICE recommendations are to avoid stockings after DVT, European recommendations are to still wear them. Both cannot be true._x000D_ _x000D_ The contradictory results of these trials have led us to design the CHAPS trial._x000D_ _x000D_ The aim of CHAPS is to confirm whether there is a real benefit of wearing stockings in addition to the standard treatment for deep vein thrombosis, which is blood thinning medication._x000D_ _x000D_ Adults with a first deep vein thrombosis can join the trial. They will be randomly allocated to receive either blood thinning medication, or blood thinning medication and an additional compression stocking. This is a tight, custom fitted stocking that they will be asked to wear whilst they are awake as much as possible for between 6-30 months. Patients will be aware of which group they are in, but will be asked not to wear the stocking when they come for their assessment. This keeps the researchers impartial._x000D_ _x000D_ To help participants remember to wear stockings they have access to an educational video, a Facebook support group, a diary and weekly SMS reminders._x000D_ _x000D_ After the trial, patients do not need to wear their stockings. As some patients find putting on a stocking tricky, we have a variety of free aids to help people use them as well as training on how to put them on. In addition we have cotton stockings to wear in summer months, more elegant stockings that can be worn out for women and stockings that resemble socks for men._x000D_ _x000D_ Patients and relatives have been involved in the design of the research, drafting this summary and will sit on our trial committees. This will mean that patients have a voice during the running of the trial. For example, this allows the voice of participants to be heard on the trial steering committee. We are working with the charity Thrombosis UK and the results of the trial will be made available on their website. Thrombosis UK will also help promote the trial on their website and help provide educational information about PTS to patients.

Lay abstract: Background_x000D_ Deep venous thrombosis (DVT) occurs in approximately 1-2 per 1000 adults worldwide and half go on to develop lifelong disability from post-thrombotic syndrome (PTS). In the recent SOX trial, 70% of patients developing DVT were of working age, potentially affecting their chances of continuing in employment. Following the unexpected failure of the ATTRACT trial to show a benefit for DVT thrombolysis, NICE have asked:_x000D_ _x000D_ “What is the effectiveness of stockings, when adherence is adequate, for preventing post thrombotic syndrome in people with confirmed deep vein thrombosis?”_x000D_ _x000D_ Aim_x000D_ To measure the difference in cumulative incidence of post-thrombotic syndrome at a median of 18 months follow up after first, acute DVT between standard clinical care (anticoagulation) and the intervention arm (a graduated compression stocking and anticoagulation)._x000D_ _x000D_ Methods_x000D_ A pragmatic, observer blind, multi-centre, randomised controlled trial for adults with first, acute lower limb DVT. Participants will undergo web based randomisation to either standard care (anticoagulation) or the intervention (anticoagulation and regular use of a graduated compression stocking). A number of low cost behavioural aids will be made available to patients in the intervention arm to aid adherence._x000D_ _x000D_ The study has an internal pilot study with the endpoint of adherence at 1 year. If adherence in the first 100 patients at 1 year is 70% of patients wearing stockings for more than half the time they are awake, with a documented reorder of stockings within 6 months, the trial will continue._x000D_ _x000D_ At a median of 18 months (range 6-30 months) patients will be followed up by an independent, blinded observer to assess their degree of post-thrombotic syndrome using the validated semi-quantitative Villalta scoring system. Quantitative analysis and oversight will via be performed through the Edinburgh CTU using a primary intention to treat analysis and a secondary analysis (causal model using instrumental variables e.g. Complier Average Causal Effect (CACE)) to explore the effect of compliance_x000D_ _x000D_ Timeline_x000D_ CHAPS is a 45-month trial with a median patient follow up of 18 months (range 6-30 months)._x000D_ _x000D_ Setup phase 6 months_x000D_ Recruitment phase 24 months_x000D_ Follow up phase further 6 months_x000D_ Endpoint adjudication 3 months_x000D_ Analysis 6 months_x000D_ _x000D_ Anticipated impact and dissemination_x000D_ The final results of CHAPS, the adherence pilot study and the cost-effectiveness analysis will be published in a high impact journal and presented at international and national vascular and haematology conferences._x000D_ _x000D_ Dissemination will be via the Thrombosis UK Facebook group to patients, Imperial College London website to the public, via peer reviewed publication for health professionals, and an email summary will be sent to participants._x000D_ _x000D_ Behavioural interventions which are shown to improve adherence will be made available to the NHS, e.g. patient education video and Facebook group for patients.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: BLOOD;CARDIOVASCULAR;SKIN