Chronic Venous InsufficiencyBESTNCT05622500
Best Endovenous Treatment, Including STenting, Versus Non-endovenous Treatment in Chronic Proximal Deep Venous Disease
A study testing Deep venous stenting and Best medical therapy in people with Chronic Venous Insufficiency and Chronic Venous Thrombosis, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Chronic Venous Insufficiency, Chronic Venous Thrombosis, Iliac Vein Stenosis
- What is being tested?
- Deep venous stenting and Best medical therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Sep 2022to 8 Apr 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, UK, W68RF
About this study
Official title: Best Endovenous Treatment, Including STenting, Versus Non-endovenous Treatment in Chronic Proximal Deep Venous Disease - the BEST Multi-centre Randomised Controlled Trial
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).
Read the 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.
- Conditions
- Chronic Venous Insufficiency, Chronic Venous Thrombosis, Iliac Vein Stenosis, Iliac Vein Obstruction, Post Thrombotic Syndrome
- Being tested
- Deep venous stenting, Best medical therapy
- Keywords
- Deep venous stenting, Intravascular ultrasound, Post thrombotic syndrome, Non-thrombotic iliac vein lesions, Proximal venous outflow obstruction, Chronic venous disease
- Medical subject headings
- Postthrombotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deep venous stentingProcedure or surgery
Also called Deep venous reconstruction, Iliac vein stenting
Endovascular reconstruction encompasses balloon venoplasty and venous stenting. A dedicated venous stent will be used, the brand of which the individual interventionist will decide.
Best medical therapyCombination product
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.
| Study group | Role | What they receive |
|---|---|---|
| Best endovenous reconstruction + best medical treatment (compression +/- anti-thrombotic therapy). | Experimental | 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). Receives: Procedure: Deep venous stenting; Combination Product: Best medical therapy |
| Best medical treatment alone (compression +/- anticoagulation). | Active comparator | The comparator arm will consist of participants receiving best medical treatment alone. Receives: Combination Product: Best medical therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (10)
Re-intervention, number of participants requiring an additional procedure.
Dichotomous outcome, defined as additional procedure undertaken to maintain or re-establish stent patency,
Measured: 6 weeks, 3 months, 6 months, 12 months
Stent patency, dichotomous outcome, number of participants with a patent stent at last follow-up.
Reported as primary, primary-assisted, secondary patency
Measured: 6 weeks, 3 months, 6 months, 12 months
Cost-effectiveness of deep venous reconstruction
ICER
Measured: 12 months
VEINES-QoL/Sym
Disease-specific quality of life measure. Standardised score, hence no meaningful min/max. High score = better quality of life.
Measured: 6 weeks, 6 months, 12 months
Villalta score
Disease severity score. Min score 0, Max score 33. High score = worse severity of disease.
Measured: 6 weeks, 6 months, 12 months
Ginsberg score, dichotomous outcome (Yes / No)
Diagnostic system for PTS (Yes /No).
Measured: 6 weeks, 6 months, 12 months
Venous ulceration, dichotomous outcome
Presence of venous ulceration on clinical examination.
Measured: 6 weeks, 6 months, 12 months
SF-36
Quality of life measure. Standardised score, 0 - 100 per section. High score = better quality of life.
Measured: 6 weeks, 6 months, 12 months
EQ-5D-5L
Quality of life measure. Scored 0 - 100 for VAS. High score = better quality of life.
Measured: 6 weeks, 6 months, 12 months
Walking distance
Walking distance, metres, self-reported.
Measured: 6 weeks, 6 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2022
- Study start3 Sep 2022
- Primary completion8 Apr 2025
- Study completion8 Apr 2025
Why it stopped: The trial failed to meet the milestones in the internal pilot of feasibility. The trial was redesigned to improve its deliverability and reduce burden to sites prior to being relaunched. Unfortunately, the trial failed to sufficiently recruit.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Venous InsufficiencyStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Superiority comparison using intention to treat analysis
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, University of Edinburgh
- Responsible party
- Sponsor
- Investigators
- Alun Davies, PhD, Study chair, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05622500
- Sponsor's protocol ID
- 22SM7477
- Acronym
- BEST
- Status last verified
- Jun 2025
- First submitted
- 7 Nov 2022
- Last updated
- 22 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Flumignan RL, Nakano LC, Flumignan CD, Baptista-Silva JC. Angioplasty or stenting for deep venous thrombosis. Cochrane Database Syst Rev. 2025 Feb 19;2(2):CD011468. doi: 10.1002/14651858.CD011468.pub2.
PubMed 39968829
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Best Endovenous Treatment, Including STenting, Versus Non-endovenous Treatment in Chronic Proximal Deep Venous Disease - the BEST Multi-centre Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT05622500
- Acronym / sponsor ID
- BEST / 22SM7477
- 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
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial failed to meet the milestones in the internal pilot of feasibility. The trial was redesigned to improve its deliverability and reduce burden to sites prior to being relaunched. Unfortunately, the trial failed to sufficiently recruit.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- British Heart Foundation, University of Edinburgh
- Study start
- 3 Sep 2022 (actual)
- Primary completion
- 8 Apr 2025 (actual)
- Study completion
- 8 Apr 2025 (actual)
- First posted
- 18 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Superiority comparison using intention to treat analysis
| Arm | Type | Receives |
|---|---|---|
| Best endovenous reconstruction + best medical treatment (compression +/- anti-thrombotic therapy). | Experimental | Procedure: Deep venous stenting, Combination Product: Best medical therapyThe 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). |
| Best medical treatment alone (compression +/- anticoagulation). | Active comparator | Combination Product: Best medical therapyThe comparator arm will consist of participants receiving best medical treatment alone. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Deep venous stentingAlso: Deep venous reconstruction, Iliac vein stentingEndovascular reconstruction encompasses balloon venoplasty and venous stenting. A dedicated venous stent will be used, the brand of which the individual interventionist will decide. | Procedure or surgery | Best endovenous reconstruction + best medical treatment (compression +/- anti-thrombotic therapy). |
| Best medical therapyCompression 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. | Combination product | Best endovenous reconstruction + best medical treatment (compression +/- anti-thrombotic therapy)., Best medical treatment alone (compression +/- anticoagulation). |
Primary outcome
Venous Clinical Severity Score (VCSS) at 6 months
Time frame: 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.
10 secondary outcomes
Re-intervention, number of participants requiring an additional procedure.
Time frame: 6 weeks, 3 months, 6 months, 12 months
Stent patency, dichotomous outcome, number of participants with a patent stent at last follow-up.
Time frame: 6 weeks, 3 months, 6 months, 12 months
Cost-effectiveness of deep venous reconstruction
Time frame: 12 months
VEINES-QoL/Sym
Time frame: 6 weeks, 6 months, 12 months
Villalta score
Time frame: 6 weeks, 6 months, 12 months
Ginsberg score, dichotomous outcome (Yes / No)
Time frame: 6 weeks, 6 months, 12 months
Venous ulceration, dichotomous outcome
Time frame: 6 weeks, 6 months, 12 months
SF-36
Time frame: 6 weeks, 6 months, 12 months
EQ-5D-5L
Time frame: 6 weeks, 6 months, 12 months
Walking distance
Time frame: 6 weeks, 6 months, 12 months
Results and safety
The study was stopped early (reason given: The trial failed to meet the milestones in the internal pilot of feasibility. The trial was redesigned to improve its deliverability and reduce burden to sites prior to being relaunched. Unfortunately, the trial failed to sufficiently recruit.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2025.
- Derived from this study: PubMed 39968829Flumignan RL, Nakano LC, Flumignan CD, Baptista-Silva JC. Angioplasty or stenting for deep venous thrombosis. Cochrane Database Syst Rev. 2025 Feb 19;2(2):CD011468. doi: 10.1002/14651858.CD011468.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alun Davies, PhD study chair
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Deep venous stenting and Best medical therapy in people with Chronic Venous Insufficiency and Chronic Venous Thrombosis, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The trial failed to meet the milestones in the internal pilot of feasibility. The trial was redesigned to improve its deliverability and reduce burden to sites prior to being relaunched. Unfortunately, the trial failed to sufficiently recruit.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venous Clinical Severity Score (VCSS) at 6 months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05622500, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.