Last updated: 13-01-2019

252 patients randomized!

On behalf of the BASICS trial executive committee we wish you a very happy 2019!

As can be seen in the tables below, randomization rates have been further increasing. With the

help of all participating centers we should be able to reach the final target of 300 randomizations

before the end of summer 2019.

To date we have a reassuringly low number of cross-overs in our trial (BMM to IAT 2, IAT to BMM 3) and a high rate of randomized eligible patients of close to 80%. After the 9th interim analysis at the end of September on 200 patients with 3 months follow-up data, the DSMB encouraged us to continue.

As you know, the Chinese BEST trial (Basilar artery occlusion Endovascular intervention versus Standard medical Treatment), with a similar protocol as BASICS, was terminated prematurely after the enrollment of 131 patients due to an excessive number of crossovers. Fourteen out of 65 patients in the control group (22%) received endovascular treatment, and in the intervention arm, 3 patients received only best medical management. Based on its pre-specified intention-to-treat analysis, the BEST trial failed to demonstrate a benefit of endovascular therapy (EVT) over best medical management. However, the as-treated-analysis (i.e. all patients who really received EVT vs. all who did not) showed statistically significant better outcomes of patients treated with EVT.

The outcome of the BEST trial has revived the discussion among stroke physicians on the need of further proof of efficacy of EVT in patients with basilar artery occlusion.

The BASICS executive committee has decided, after thorough discussion, to continue the trial and to recommend to all centers who agree that there is still equipoise to continue randomization.

This decision was based on the following arguments:

1)The reasons why we started our trial, and continued the trail despite clear evidence of efficacy of EVT in the anterior circulation, remain valid. The BASICS Registry and several meta-analyses thereafter, have failed to show efficacy of endovascular treatment in patients with basilar artery occlusion. BEST has not reached its predefined endpoint, so there is still the scientific need to establish EVT as the treatment of choice for basilar artery occlusion.

2)Although the as-treated-analysis in BEST shows statistical significance, BEST and BASICS have, like all major phase III randomized clinical trials, used the intention-to-treat results as primary outcome. The intention-to-treat approach provides an unbiased comparison among the treatment groups. Intention-to-treat analyses are done to avoid the effects of crossover and dropout, which may lead to incomparability between the treatment groups in a study. An as-treated-analysis is good for phase II trials to show “principle of proof”, but insufficient to proof efficacy in every day clinical practice.

3)If there was overwhelming efficacy of EVT over BMM, the BASICS interim analysis would have shown it, and the trial would already have been halted; this is not the case according to the DSMB, despite the fact that the last interim analysis of BASICS was based on far more patients than randomized in BEST. Therefore, scientific equipoise persists.

4)We need not only to know whether this treatment works, but also to which extent, and for which subgroups (minor/major stroke, earlier vs. later treatment etc.). Therefore, BASICS is likely to add substantially more information about the best treatment strategy in patients with basilar artery occlusion.

In summary, the executive committee believes that after the presentation of the BEST results, sufficient equipoise remains to continue the BASICS trial in its current form. BASICS has been a challenging trial from the very start and remains so, and we are grateful to your efforts to keep randomizing every eligible patient.

The next interim analysis on 225 patients with 3 months follow-up data is due in January 2019.

We hope to be able to complete our trial, within the near future, with you active participation

Kind regards,

Wouter Schonewille

On behalf of the BASICS executive committee