BEST

• Research type

  Research Study

• Full title

  Best Endovenous treatment, including STenting, versus best non-endovenous treatment in chronic proximal deep venous disease – the BEST multi-centre randomised controlled trial

• IRAS ID

  308755

• Contact name

  Alun Huw Davies

• Contact email

  a.h.davies@imperial.ac.uk

• Sponsor organisation

  Imperial College London

• Clinicaltrials.gov Identifier

  NCT05622500

• Duration of Study in the UK

  3 years, 11 months, 31 days

• Research summary

  Research Summary: THE PROBLEM
  Venous disease is a term used to describe problems that patients may have with the veins in their legs, including blockages in the veins or blood travelling the wrong way in the veins. Chronic obstruction of the iliac veins and inferior vein cava can be secondary to a clot in vein known as post-thrombotic syndrome (PTS) or due to a narrowing known as non-thrombotic iliac vein lesions (NIVLs). Clots in the lower limb veins, known as deep vein thrombosis (DVT) are common. Following a DVT, up to 50% of patients develop PTS. Venous disease can cause heaviness, swelling, itching, aching and problems with doing everyday tasks. Sometimes, when the blood rests near the ankles for a long time, this can cause the skin to break down and a wound (ulcer) to develop.

  THE STUDY
  The main treatments for chronic venous disease are: wearing tight elastic stockings and/or thinning the blood with medicines, or trying to open the narrowed or blocked vein with a stent.
  A deep venous stent is one that is made to be placed high-up in the leg veins. This can help the flow of blood from the leg back to the heart. Placing a stent in the veins is generally a safe procedure but it is unclear if they improve the problems that people with venous disease have. This study will investigate adults with venous disease secondary to either PTS or NIVLs. The study will randomise them to either best endovenous therapy (including venoplasty and deep venous stenting) or standard therapy (compression +/- anticoagulation). The main study outcome will be the severity of venous disease at 6 months, measured using the Venous Clinical Severity Score (VCSS). Participants will be monitored closely will clinical assessment and ultrasound scans at 6 weeks, 6 months and 1 year.

  Summary of Results: Why was this study done?

  The BEST trial was designed to find out whether iliac vein stenting helps people with chronic venous disease more than standard medical treatment alone. Iliac vein stenting is a procedure that places a small metal tube (a stent) in a vein to help improve blood flow.

  Although this procedure is increasingly used in clinical practice, there is little high-quality research comparing it directly with non-surgical treatment. The aim of the trial was to provide reliable evidence to help doctors and patients make informed treatment decisions.

  The study was designed together with patients, vascular specialists, and research experts.

  The study was originally planned to run for four years, including:

  1. Setting up the trial and gaining approvals
  2. Recruiting participants from hospitals across the UK and potentially Europe
  3. Following participants for 12 months after treatment

  Early review of recruitment

  After the first six months of recruitment, the trial team carried out a planned review to assess whether the study was progressing as expected. This is referred to as an internal pilot, where there is the opportunity to close the trial early if it looks unlikely to succeed in reaching its objectives.

  At that time:
  • 6 out of the 10 hospitals had started recruiting participants (this was on track)
  • 36 potential participants had been assessed for eligibility (this was lower than expected)
  • 10 participants had joined the trial (this was far lower than expected)

  Recruitment was lower than expected, meaning the trial was unlikely to reach the number of participants needed within the planned timeline.

  Several reasons contributed to this:
  • Some hospitals took longer than expected to complete local research approvals;
  • Some patients preferred to choose their treatment rather than be randomly allocated;
  • Delays occurred in arranging diagnostic tests needed before enrolment; and
  • The number of eligible patients seen in clinics was lower than anticipated.
  Changes made to improve the study

  To try to improve recruitment and make the trial more feasible, the research team, under the guidance of expert patients and key stakeholders, redesigned the study.

  Key changes included:
  • Focusing our efforts only on patients with post-thrombotic syndrome;
  • Reducing the number of participants required while still being able to answer the question reliably (this was based on new data from similar research recently undertaken in parallel to the trial);
  • Removing some study visits and scans to reduce the burden on participants and hospitals; and
  • Exploring opening recruitment at ‘high volume’ treatment sites in across Europe.

  Unfortunately, after negotiations with European sites, this was deemed too costly to proceed with. The other changes and the redesigned study was approved by ethics panel and relaunched in February 2024.

  What happened after the relaunch

  Despite the changes:
  • Recruitment remained very low; and
  • Some hospitals withdrew as the trial costs were too high when compared to the financial reimbursements received.

  Because it was unlikely that the study could recruit enough participants to answer the research question, the trial team made the decision to close the study in March 2025.

  Results from participants who took part
  We were able to collect lots of information and learned a number of lessons in relation to delivering a trial in this area of research, however, the number of participants was too small to provide any reliable conclusions on the effectiveness of venous stenting.

  Key lessons included:
  • Patients often have strong preferences for treatment, which can make randomisation difficult – there are a number of steps we can take to overcome this but most of them involve identifying participants earlier on in the referral pathway (such as at the GP or local hospital);
  • Research approvals and study setup in hospitals are taking an increasingly long period of time to undertake and trial set-up schedules should be increased (with a corresponding increase in funding for this step);
  • The research design process has its limitations; there is an increasing need for pilot studies;
  • Some eligible patients may not be referred to specialist centres where trials take place, there is a need for haematology-based identification centres in future trials of this nature; and
  • Research studies that are not commercially funded can struggle to compete for resources.
  These lessons will help improve the design of future studies in this area.

  What happens next?

  There is still a clear need for high-quality research to determine whether venous stenting provides additional benefit compared with medical treatment alone. There is an ongoing study in the USA which has also struggled to recruit. We are hopeful that the data from this study, and study for other trials that have closed earlier, will be able to contribute to that dataset.

  Future studies in this area will need to consider new approaches to recruitment and study design to help answer this important question. A scientific paper will be published discussing these difficulties in order to facilitate this.
  

• REC name

  West Midlands - South Birmingham Research Ethics Committee

• REC reference

  22/WM/0067

• Date of REC Opinion

  4 Apr 2022

• REC opinion

  Further Information Favourable Opinion