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Best Endovenous Treatment, Including STenting, Versus Non-endovenous Treatment in Chronic Proximal Deep Venous Disease (BEST)

Primary Purpose

Chronic Venous Insufficiency, Chronic Venous Thrombosis, Iliac Vein Stenosis

Status
Recruiting
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Deep venous stenting
Best medical therapy
Sponsored by
Imperial College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Venous Insufficiency focused on measuring Deep venous stenting, Intravascular ultrasound, Post thrombotic syndrome, Non-thrombotic iliac vein lesions, Proximal venous outflow obstruction, Chronic venous disease

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Adult patients with chronic venous disease secondary to chronic proximal thrombotic or nonthrombotic stenosis or occlusion Disease in iliac and/or caval deep venous system(s) CEAP clinical C3, C4, C5, C6 or symptoms of venous claudication Anatomically suitable for endovenous reconstruction Exclusion Criteria: Contraindications to stenting (e.g. anatomically unsuitable, contrast allergy) Contraindications to prolonged anticoagulation Existing diagnosis of profound pro-thrombotic states (Beh et's, anti-phospholipid syndrome) Caval occlusion at or proximal to the level of the renal veins Open / hybrid open-endovascular deep venous intervention Pregnancy Inability to provide consent Need to intervene caudal to common femoral vein confluence to achieve inflow Participants that have tested positive for coronavirus within the last 3 months

Sites / Locations

  • Imperial College Healthcare NHS TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Best endovenous reconstruction + best medical treatment (compression +/- anti-thrombotic therapy).

Best medical treatment alone (compression +/- anticoagulation).

Arm Description

The intervention arm consists of participants undergoing best endovenous reconstruction under the guidance of intra-vascular ultrasound in addition to best medical treatment (compression +/- antithrombotic therapy).

The comparator arm will consist of participants receiving best medical treatment alone.

Outcomes

Primary Outcome Measures

Venous Clinical Severity Score (VCSS) at 6 months
Disease severity score. Venous clinical severity score (VCSS) encompasses nine hallmarks of chronic venous disease, each scored on a severity scale from 0 to 3. Min score 0, Max score 30. High score = worse severity of disease.

Secondary Outcome Measures

Re-intervention, number of participants requiring an additional procedure.
Dichotomous outcome, defined as additional procedure undertaken to maintain or re-establish stent patency,
Stent patency, dichotomous outcome, number of participants with a patent stent at last follow-up.
Reported as primary, primary-assisted, secondary patency
Cost-effectiveness of deep venous reconstruction
ICER
VEINES-QoL/Sym
Disease-specific quality of life measure. Standardised score, hence no meaningful min/max. High score = better quality of life.
Villalta score
Disease severity score. Min score 0, Max score 33. High score = worse severity of disease.
Ginsberg score, dichotomous outcome (Yes / No)
Diagnostic system for PTS (Yes /No).
Venous ulceration, dichotomous outcome
Presence of venous ulceration on clinical examination.
SF-36
Quality of life measure. Standardised score, 0 - 100 per section. High score = better quality of life.
EQ-5D-5L
Quality of life measure. Scored 0 - 100 for VAS. High score = better quality of life.
Walking distance
Walking distance, metres, self-reported.

Full Information

First Posted
November 7, 2022
Last Updated
April 17, 2023
Sponsor
Imperial College London
Collaborators
British Heart Foundation, University of Edinburgh
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1. Study Identification

Unique Protocol Identification Number
NCT05622500
Brief Title
Best Endovenous Treatment, Including STenting, Versus Non-endovenous Treatment in Chronic Proximal Deep Venous Disease
Acronym
BEST
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 3, 2022 (Actual)
Primary Completion Date
November 1, 2025 (Anticipated)
Study Completion Date
May 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
British Heart Foundation, University of Edinburgh

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Superiority comparison using intention to treat analysis
Masking
InvestigatorOutcomes Assessor
Masking Description
Assessor-blinded (single blind)
Allocation
Randomized
Enrollment
328 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Best endovenous reconstruction + best medical treatment (compression +/- anti-thrombotic therapy).
Arm Type
Experimental
Arm Description
The intervention arm consists of participants undergoing best endovenous reconstruction under the guidance of intra-vascular ultrasound in addition to best medical treatment (compression +/- antithrombotic therapy).
Arm Title
Best medical treatment alone (compression +/- anticoagulation).
Arm Type
Active Comparator
Arm Description
The comparator arm will consist of participants receiving best medical treatment alone.
Intervention Type
Procedure
Intervention Name(s)
Deep venous stenting
Other Intervention Name(s)
Deep venous reconstruction, Iliac vein stenting
Intervention Description
Endovascular reconstruction encompasses balloon venoplasty and venous stenting. A dedicated venous stent will be used, the brand of which the individual interventionist will decide.
Intervention Type
Combination Product
Intervention Name(s)
Best medical therapy
Intervention Description
Compression stockings encompass a range of therapies used to provide an externally applied graduated-pressure up the length of the limb aiming to improve venous function and decrease lower limb swelling. Compression stockings can be classified by size and grade, i.e. the pressure the stockings applies to the limb. For the purpose of this trial Class II and Class III graduated compression stockings should be used, with the aim of providing Class III if tolerated. Antithrombotic agents include, but are not limited to: warfarin (titrated to international normalised ratio, INR), apixaban, rivaroxaban, aspirin, and clopidogrel.
Primary Outcome Measure Information:
Title
Venous Clinical Severity Score (VCSS) at 6 months
Description
Disease severity score. Venous clinical severity score (VCSS) encompasses nine hallmarks of chronic venous disease, each scored on a severity scale from 0 to 3. Min score 0, Max score 30. High score = worse severity of disease.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Re-intervention, number of participants requiring an additional procedure.
Description
Dichotomous outcome, defined as additional procedure undertaken to maintain or re-establish stent patency,
Time Frame
6 weeks, 3 months, 6 months, 12 months
Title
Stent patency, dichotomous outcome, number of participants with a patent stent at last follow-up.
Description
Reported as primary, primary-assisted, secondary patency
Time Frame
6 weeks, 3 months, 6 months, 12 months
Title
Cost-effectiveness of deep venous reconstruction
Description
ICER
Time Frame
12 months
Title
VEINES-QoL/Sym
Description
Disease-specific quality of life measure. Standardised score, hence no meaningful min/max. High score = better quality of life.
Time Frame
6 weeks, 6 months, 12 months
Title
Villalta score
Description
Disease severity score. Min score 0, Max score 33. High score = worse severity of disease.
Time Frame
6 weeks, 6 months, 12 months
Title
Ginsberg score, dichotomous outcome (Yes / No)
Description
Diagnostic system for PTS (Yes /No).
Time Frame
6 weeks, 6 months, 12 months
Title
Venous ulceration, dichotomous outcome
Description
Presence of venous ulceration on clinical examination.
Time Frame
6 weeks, 6 months, 12 months
Title
SF-36
Description
Quality of life measure. Standardised score, 0 - 100 per section. High score = better quality of life.
Time Frame
6 weeks, 6 months, 12 months
Title
EQ-5D-5L
Description
Quality of life measure. Scored 0 - 100 for VAS. High score = better quality of life.
Time Frame
6 weeks, 6 months, 12 months
Title
Walking distance
Description
Walking distance, metres, self-reported.
Time Frame
6 weeks, 6 months, 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patients with chronic venous disease secondary to chronic proximal thrombotic or nonthrombotic stenosis or occlusion Disease in iliac and/or caval deep venous system(s) CEAP clinical C3, C4, C5, C6 or symptoms of venous claudication Anatomically suitable for endovenous reconstruction Exclusion Criteria: Contraindications to stenting (e.g. anatomically unsuitable, contrast allergy) Contraindications to prolonged anticoagulation Existing diagnosis of profound pro-thrombotic states (Beh et's, anti-phospholipid syndrome) Caval occlusion at or proximal to the level of the renal veins Open / hybrid open-endovascular deep venous intervention Pregnancy Inability to provide consent Need to intervene caudal to common femoral vein confluence to achieve inflow Participants that have tested positive for coronavirus within the last 3 months
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alun Davies, PhD
Phone
0208 3311 7320
Email
BESTtrial@imperial.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Matthew Machin, MBBS
Phone
(0) 208 3311 7320
Email
m-machin@live.co.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alun Davies, PhD
Organizational Affiliation
Imperial College London
Official's Role
Study Chair
Facility Information:
Facility Name
Imperial College Healthcare NHS Trust
City
London
State/Province
UK
ZIP/Postal Code
W68RF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Machin, MBBS
Phone
07414869227
Email
matthew.machin12@imperial.ac.uk
First Name & Middle Initial & Last Name & Degree
Alun Huw Davies, PhD

12. IPD Sharing Statement

Learn more about this trial

Best Endovenous Treatment, Including STenting, Versus Non-endovenous Treatment in Chronic Proximal Deep Venous Disease

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