Clinical trial NCT05622500: Best Endovenous Treatment, Including STenting, Versus Non-endovenous Treatment in Chronic Proximal Deep Venous Disease
Official title: Best Endovenous Treatment, Including STenting, Versus Non-endovenous Treatment in Chronic Proximal Deep Venous Disease - the BEST Multi-centre Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Venous Insufficiency
Chronic Venous Thrombosis
Iliac Vein Stenosis
Iliac Vein Obstruction
Post Thrombotic Syndrome
Keywords: Deep venous stenting
Intravascular ultrasound
Post thrombotic syndrome
Non-thrombotic iliac vein lesions
Proximal venous outflow obstruction
Chronic venous disease
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
name: University of Edinburgh
First posted: 2022-11-18
Enrollment: 328
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Superiority comparison using intention to treat analysis
Primary purpose: TREATMENT

Brief summary: 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. Despite sparse evidence, rates of venous stenting for PTS and NIVLs are increasing.

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). Included participants will have chronic venous disease (CEAP classification 3 - 6) secondary to proximal deep venous disease. The primary outcome is severity of venous disease at 6 months as ascertained by the Venous Clinical Severity Score (VCSS).

Detailed description: Symptomatic chronic obstructive lesions of the iliac veins and inferior vein cava can be secondary to post-thrombotic lesions caused by a deep vein thrombosis (DVT) or due to non-thrombotic iliac vein lesions (NIVLs). DVT has an annual incidence of 148 per 100,000 person years in Europe. Following a DVT, up to 50% of patients develop post thrombotic syndrome (PTS), defined as "chronic venous symptoms or signs secondary to DVT" i.e. lifelong leg pain, oedema and skin changes. Furthermore, the subsequent rate of venous ulceration is high with up to 29% of those with PTS suffering from active or healed venous ulcers. The pathophysiology of PTS is thought to be sustained venous hypertension from a combination of venous outflow obstruction and valvular incompetence. NIVLs are due to external compression or intrinsic lesions that reduce the venous drainage through the iliac venous system. This, in turn, can lead to chronic venous insufficiency and also increase the risk of DVT. NIVLs contribute to the significant morbidity and cost associated with CVD. NIVLs can be demonstrated on imaging as a stenosed iliac vein or in an iliac vein of normal diameter with intrinsic lesions.

Rates of venous stenting for PTS and NIVLs are rapidly increasing. However, sparse evidence exists to support the use of venous stenting and clinical guidelines reflect this. Endovenous stenting is being increasingly used as a treatment option for individuals with complications relating to chronic venous disease such as skin changes, ulceration, debilitating symptoms, and functional impairment. However, a recent systematic review of sixteen eligible studies, none of which were RCTs, concluded that: "The quality of evidence to support the use of deep venous stenting to treat chronic obstructive disease is currently weak. The treatment does however appear promising and is safe and should therefore be considered as a treatment option while the evidence base is improved". Many of the studies employed stents which were not primarily designed for use in the venous system. The role of endovenous reconstruction in the context of patients with PTS and NIVLs, including deep venous stenting using modern stents designed specifically for use in the venous system, remains to be elucidated in a well-designed RCT.

The rational for the proposed study is supported by both haemodynamic and clinical evidence. Retrospective cohorts of deep venous stenting in PTS and NIVLs have yielded promising results. Pre-clinical research suggests that common femoral vein pressure is increased in post thrombotic venous obstruction. It has been demonstrated that deep venous stenting improves mean ambulatory venous pressures and therefore should reduce the symptomology experienced by the individual. Furthermore, venous stents are specifically designed to be uncovered and rigid, aiming to keep the aspect ratio of the stent at a 1:1 ratio, to minimise outflow obstruction and increase venous return.

Eligibility criteria: Inclusion Criteria:

1. Adult patients with chronic venous disease secondary to chronic proximal thrombotic or nonthrombotic stenosis or occlusion
2. Disease in iliac and/or caval deep venous system(s)
3. CEAP clinical C3, C4, C5, C6 or symptoms of venous claudication
4. Anatomically suitable for endovenous reconstruction

Exclusion Criteria:

1. Contraindications to stenting (e.g. anatomically unsuitable, contrast allergy)
2. Contraindications to prolonged anticoagulation
3. Existing diagnosis of profound pro-thrombotic states (Beh et's, anti-phospholipid syndrome)
4. Caval occlusion at or proximal to the level of the renal veins
5. Open / hybrid open-endovascular deep venous intervention
6. Pregnancy
7. Inability to provide consent
8. Need to intervene caudal to common femoral vein confluence to achieve inflow
9. Participants that have tested positive for coronavirus within the last 3 months

Primary outcomes:
measure: Venous Clinical Severity Score (VCSS) at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Re-intervention, number of participants requiring an additional procedure.
timeFrame: 6 weeks, 3 months, 6 months, 12 months
measure: Stent patency, dichotomous outcome, number of participants with a patent stent at last follow-up.
timeFrame: 6 weeks, 3 months, 6 months, 12 months
measure: Cost-effectiveness of deep venous reconstruction
timeFrame: 12 months
measure: VEINES-QoL/Sym
timeFrame: 6 weeks, 6 months, 12 months
measure: Villalta score
timeFrame: 6 weeks, 6 months, 12 months
measure: Ginsberg score, dichotomous outcome (Yes / No)
timeFrame: 6 weeks, 6 months, 12 months
measure: Venous ulceration, dichotomous outcome
timeFrame: 6 weeks, 6 months, 12 months
measure: SF-36
timeFrame: 6 weeks, 6 months, 12 months
measure: EQ-5D-5L
timeFrame: 6 weeks, 6 months, 12 months
measure: Walking distance
timeFrame: 6 weeks, 6 months, 12 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
state: UK
Study officials:
affiliation: Imperial College London
name: Alun Davies, PhD
role: STUDY_CHAIR
References: