The findings published by Konstantinos Katsanos and colleagues in JAHA quickly sparked wide-spread debate across the vascular community, as the meta-analysis’ implications and questions raised for use of paclitaxel-coated devices are discussed. The data had a near-immediate impact on practice, as the SWEDEPAD 1 and 2 trials stopped enrolment within days of the publication. Shortly thereafter, the BASIL-3 trial similarly paused recruitment, stating there were concerns about patient safety following the outcomes of the meta-analysis of randomised controlled trials using paclitaxel treatments.
The halted trials were aiming to evaluate various paclitaxel devices for patients with peripheral arterial disease. The SWEDEPAD (Swedish drug-elution trial in peripheral arterial disease) project is designed to test the hypothesis that drug-eluting technology is superior to conventional endovascular treatment in terms of important clinical outcomes, when applied on infrainguinal (femoropopliteal and/or infrapopliteal) obstructive vascular lesions. The SWEDEPAD project consists of two separate parallel studies, SWEDEPAD 1 and SWEDEPAD 2, each defined by the severity of peripheral arterial disease. As noted on clinicaltrials.gov, “patients with critical limb ischaemia are allocated to SWEDEPAD 1 and patients with intermittent claudication are allocated to SWEDEPAD 2.” SWEDEPAD 1 has a planned enrolment of 2,400 patients and SWEDEPAD 2 of 1,333 patients.
An update on the trial website states there is currently a “temporary haltof recruitement” to both trials. The statement reads: “Following the recent publication of a meta-analysis by Katsanos et al, the SWEDEPAD data safety and management committee (DSMC) did an interim safety analysis of SWEDEPADs prespecified safety variables. The results of the metaanalysis, and of our own interim safety analysis, prompted us to on December 10, 2018 temporarily halt recruitment of patients to SWEDEPAD 1 and 2.
“We are now conducting a thorough in-depth analysis of all patients randomised in SWEDEPAD 1 and 2 with respect to this safety warning. This will require additional data and it is therefore decided to prolong the temporary halt of inclusions at least until early February 2019.”
To date, SWEDEPAD 1 has randomised 1,480 patients and 810 have been randomised in SWEDEPAD 2.
Recruitment halt follows steady decline in BASIL-3 enrolment rates
BASIL-3 had already been experiencing difficulties with recruitment, and investigators struggled to reach their enrolment milestone targets throughout. At the Vascular Societies’ Annual Scientific Meeting 2018 (VSASM; 28–30 November, Glasgow, UK), BASIL lead investigator Andrew Bradbury (Heart of England NHS Foundation Trust in Birmingham, UK) warned of difficulties with enrolling patients to the study, saying he was “rather worried about BASIL-3”. Bradbury called on the community of vascular and endovascular surgeons to “explore why it has become difficult to recruit to a trial that actually should be pretty easy— three endo options in a very common procedure, and a very big patient population”.
The research is a joint initiative from University Hospitals Birmingham, the University of Birmingham Clinical Trials Unit (BCTU), and the National Institute for Health Research (NIHR).
“It should be an easy trial, really, because lots and lots of people have femoropop-endo for critical limb ischaemia and, from a patient experience point of view, the three arms are virtually identical,” he said. “We started at the beginning recruiting ahead of target, so why things have fallen off quite so badly in recent times is kind of difficult to understand.”
BASIL-2 is randomising patients with critical limb ischaemia who require infrapopliteal intervention either to vein bypass first or best endovascular treatment first. “Best endovascular treatment can be whatever it is you want to use,” said Bradbury.
Meanwhile, the BASIL-3 trial has no surgical arm. Participants are patients receiving femoropopliteal intervention for critical limb ischaemia and for whom it has already been decided that they will receive endovascular treatment rather than a bypass. They are randomised to either percutaneous transluminal angioplasty with a bailout bare metal stent (BMS), angioplasty with a paclitaxel drug-coated balloon (DCB) with or without a BMS, or to a paclitaxel drug-eluting stent with or without a BMS.
The original target for BASIL 3 was 861 patients. Three years after enrolment began investigators have now randomised 407 patients, less than 50% of the desired amount. Before the newly published data raised questions about paclitaxel treatments and caused the BASIL-3 enrolment to be put on hold, Bradbury acknowledged: “[Patient numbers were] quite a long way below what we had hoped for [for some months], but nevertheless pretty steady. But, since the summer, there has been a bit of a fall off. We have almost stopped recruiting to this trial, and I am not quite sure why that is. But it is quite a big problem, and I do not think any of us really want this to happen to the BASIL trial.”