Chronic obstruction of the iliac veins or inferior vena cava can occur as a result of deep vein thrombosis (DVT), or due to extrinsic compression in non-thrombotic iliac vein lesions (NIVLs). This obstruction can manifest as post-thrombotic syndrome (PTS) after DVT or as chronic venous disease (CVD) in NIVL. Little evidence exists to support the use of deep venous stents in established PTS or NIVLs, and the evidence for its use in the prevention of PTS is inconclusive. This lack of evidence is reflected in the European Society for Vascular Surgery 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of the Lower Limbs providing a class 2a, level B recommendation for endovascular treatment in those with iliac vein outflow obstruction. Furthermore, a provisional health economic analysis over 5 years found that the incremental cost-effectiveness ratio of stenting versus no stenting over a 5 year period was between €9,000 and €62,000 per quality-adjusted life year (QALY) for treatment of established PTS. Despite sparse evidence, significant costs, and a re-intervention rate of up to 43% in the first year, rates of venous stenting for PTS and NIVLs are increasing. Aims of the trial: 1. Does undertaking deep venous procedures, including venoplasty and deep venous stenting, in those suffering from PTS or CVD secondary to NIVL improve clinical measures of chronic venous disease and quality of life? 2. Is undertaking deep venous procedures, including venoplasty and deep venous stenting, safe? 3. Is undertaking deep venous procedures, including venoplasty and deep venous stenting, cost-effective?

We present a pragmatic, observer-blind, multi-centre, randomised-controlled trial for adults with CVD secondary to either PTS or NIVLs randomised to either best endovenous therapy (including venoplasty and deep venous stenting) or standard therapy (compression +/- anticoagulation) funded by The British Heart Foundation, UK. Included participants will have chronic venous disease (CEAP classification 3 - 6) secondary to proximal deep venous disease. Endovenous reconstruction will be undertaken in dedicated venous centres aligning to a technical protocol highlighting best practice, including dedicated venous stents and the use of intravascular ultrasound. Ultrasound surveillance will be mirrored in the control arm to minimise bias. The primary outcome is severity of venous disease at 6 months as ascertained by the Venous Clinical Severity Score (VCSS). Secondary outcomes include mean change in Villalta score, VEINES-QoL, stent patency and cost-effectiveness. An intention-to-treat analysis will be undertaken for the primary outcome, this will capture failed interventions. Crossover from best medical therapy to the intervention arm will be recorded and a subsequent per protocol analysis will be undertaken. At 90% power and a 5% level of significance on the primary outcome of change over baseline VCSS at 6 months, the study will detect the minimally important clinically significant mean change of 4 units, assuming a standard deviation of 8 units, by recruiting 328 participants. This participant number accounts for varied disease severity (i.e. a large standard deviation), clustering of surgical intervention and standard care, loss to follow-up, and crossover of participants. The analysis will be powered for both pathology types: PTS and CVD secondary to NIVLs. The study will have a vanguard phase in which we will (a) assess the feasibility of recruitment and (b) check the assumptions behind the sample size, in particular the assumed standard deviation and aggregated mean score for primary outcome of change over baseline VCSS at 6 months.

We anticipate the results from this trial will guide international European guidelines on the management of chronic venous disease secondary to proximal outflow disease.

This trial will provide level A evidence to guide the practice of deep venous stenting in the treatment of chronic venous disease.