BASIL-3 Pause to Recruitment

Statement issued Friday 06 June 2019

We are writing to you to inform you of an update regarding the BASIL-3 trial which, you’ll be aware was suspended to recruitment in December 2018 following a meta-analysis published in JAHA which indicated a trend to increased mortality for PAD patients receiving paclitaxel coated devices (89% of the patients in the meta-analysis had intermittent claudication, not CLTI). 

As of the 4th June 2019, the independent Expert Advisory Group (EAG) established by the MHRA released a report stating that the use of paclitaxel coated balloons and paclitaxel eluting stents should still be considered in patients with limb threatening ischaemia and specifically states the BASIL-3 trial should consider resuming recruitment. 

“BASIL 3 and other suspended randomised controlled trials involving patients with critical limb ischaemia, should consider resumption in recruitment” page 10, MHRA Paclitaxel EAG Recommendations June 2019

 This report can be viewed here.

The MHRA have agreed with the EAG, as per the Medical Device Alert (MDA) (MDA/2019/023) released on 4th June 2019 confirming the use of these devices is still an appropriate option in accordance with NICE guidance for patients with critical limb ischemia.  .

Global Vascular Guidelines (GVG) have released new guidelines on the management of chronic limb threatening ischaemia.   This includes a statement on the safety of paclitaxel-eluting devices which states:

“…the risks and benefits of treatment for CLTI, including drug-eluting devices, need to be examined with appropriately controlled prospective studies that are specific to the CLTI population, the execution of randomised controlled-trials involving PTX-eluting devices in CLTI, with appropriate safety monitoring and regulatory oversight are important to the vascular community.” Page 104S, Conte et al, GVG on management of CLTI June 2019

The GVG is endorsed by the VSGBI and BSIR.   

 The BASIL-3 team and the HTA met on the 4th June to discuss the future of the trial and the new statement from the MHRA.  The Trial Steering Committee, patients and the HTA have all expressed support in re-opening BASIL-3 to recruitment.  

In light of this, we are planning to re-open BASIL-3 to recruitment following ethics approval by mid to late September of this year.  We will keep you informed of all new information and actions as to how we will progress with the trial.

Global vascular guidelines on the management of chronic limb-threatening ischemia. Journal of Vascular Surgery, 69(6), pp.3S-125S.e40.

DOI:  https://doi.org/10.1016/j.jvs.2019.02.016

Statement issued Tuesday 22 January 2019

The independent BASIL-3 Trial Steering Committee (TSC) met again on Friday 19January 2019 to review further the information and opinions, including from the BASIL-3 Data Monitoring Committee (DMC), that it has received since it recommended that recruitment to BASIL-3 be paused in the light of the publication of the Katsanos meta-analysis.

The TSC and DMC have agreed that the pause should not be lifted at the present time and that the existing 411 participants should continue to be followed up as per the existing protocol.

The TSC is continuing to work with a multi-disciplinary group of clinicians based in the UK and overseas, the funding body (NIHR HTA), the ethics committee, regulatory authorities, and industry to determine if and when it would be appropriate to resume recruitment.

The TSC has carefully considered the question of whether it would be appropriate to contact trial participants.

The TSC have decided not to do so at this time as no safety signal has been identified specifically within the BASIL-3 Trial or the wider population with chronic limb threatening ischaemia and there is currently no reason to alter the management of existing participants in the trial.

The TSC is keeping this matter under close review and will inform all concerned of any changes in the situation.

 

Statement issued Friday 14 December 2018

Dear Participating Centre,

Following our email communication of the 13th December, 2018, informing you that recruitment to BASIL-3 is currently paused, we can further inform you that the Trial Management Committee, with the attendance of the Chair of the Trial Steering Committee (TSC) and the Director of BCTU (on behalf of the Sponsor) met earlier today.

We would like to inform you that recruitment will remain paused whilst the TSC reviews the trial data within the recent JAHA meta-analysis. This is anticipated to occur by January 2019. We will shortly be issuing a questionnaire to ascertain your views pertaining to the use of drug-eluting technologies locally.

We are currently considering whether this new information should alter our follow-up regime and whether we should inform patients. At the moment we do not recommend that you contact BASIL-3 patients until we have completed our investigations. Please let us know if this conflicts with any local policies and procedures.

The BASIL-3 Trial Statisticians are currently working on a report to the DMC to urgently review the BASIL-3 data for any early indications of increased mortality in any of the treatment groups or combination of treatment groups. Therefore, please ensure your trial data are up to date and sent to the Trials Office as soon as possible.

These processes are necessary steps before a definitive view on the future of BASIL-3 can be formed. Any such view will also require ratification by both the TSC and the funder before any implications can then be appropriately incorporated into amended trial documentation.

We will inform you of progress as appropriate throughout, and thank you for your commitment to BASIL-3 thus far and your patience during this time.

 

Statement issued Thursday 13 December 2018

A recently published systematic review and meta-analysis of randomised controlled trials of patients undergoing treatment of femoro-popliteal disease with paclitaxel drug coated balloons (DCB) and drug eluting stents (DES) has reported a higher all-cause mortality at 2 and 5 years when compared to those not receiving paclitaxel DCB and DES (https://www.ahajournals.org/doi/10.1161/JAHA.118.011245).

Whilst the population of the reviewed trials differs from those in the BASIL-3 trial, it is clearly important new information that may cause concerns for the BASIL-3 trial in relation to patient safety.  As such, it raises the need to consider whether changes to the trial protocol and patient information are required.  We have therefore decided to suspend recruitment to the trial, pending further discussions.

This decision has been communicated to the Ethics Committee and NIHR HTA.  We are collecting further information and consulting with the Data Monitoring Committee and other parties, following which the Trial Steering Committee (TSC) will meet to consider the next steps.

Pending a further decision by the TSC, we would be grateful if centres would continue to follow-up BASIL-3 participants in-line with the current protocol but not attempt to recruit new patients into the trial (the randomisation service has been suspended).

We will update this page regularly to keep you fully informed of developments as they occur.