Safety and efficacy of direct versus conventional transfer to angiography suite in patients with severe acute stroke treated with thrombectomy (DIRECT ANGIO) in France: a multicentre, open-label, blinded-endpoint, randomised controlled trial.

The trial was stopped early for safety reasons after interim analysis revealed increased symptomatic intracranial haemorrhage in the DTAS group.

• The trial steering committee permanently stopped the trial on Dec 1, 2023, following an interim analysis done on Sept 27, 2023.
• The trial enrolled 115 patients between July 9, 2020, and April 18, 2023, across ten comprehensive stroke centres in France.
• 57 patients were assigned to DTAS and 58 to the conventional pathway.
• Early stopping due to safety reasons limits the precision of effect estimates on the primary and secondary outcomes.

The risk of symptomatic intracranial haemorrhage was significantly increased in the DTAS group compared with the conventional group.

• Symptomatic intracranial haemorrhage occurred in five (15%) of 34 patients in the DTAS group versus zero (0%) of 42 in the conventional group.
• Adjusted odds ratio was 11.0 (95% CI 1.28–1406).
• This was one of the main safety outcomes of the trial.
• The wide confidence interval reflects the small sample size resulting from early trial termination.

All-cause mortality at 90 days did not differ significantly between the DTAS and conventional groups.

• Mortality occurred in ten (18%) of 56 patients in the DTAS group versus six (11%) of 53 in the conventional group.
• Adjusted odds ratio was 1.65 (95% CI 0.52–5.55).
• All-cause mortality at 90 days was a prespecified main safety outcome.

Functional independence at 90 days did not differ significantly between the DTAS and conventional pathway groups.

• Functional independence (modified Rankin Scale score 0–2) was reached in 20 (36%) of 56 participants in the DTAS group versus 22 (42%) of 53 in the conventional group.
• Adjusted odds ratio was 0.73 (95% CI 0.32–1.69).
• This was the primary efficacy outcome assessed in the intention-to-treat population.
• The intention-to-treat population included all randomly assigned patients regardless of diagnosis, imaging findings, or treatments received.

The study population consisted of adult patients with acute severe neurological deficit highly suggestive of large vessel occlusion admitted within 5 hours of symptom onset.

• Eligible patients had unilateral motor deficit with a score ≥5 plus a cortical symptom with a score ≥1 on the National Institutes of Health Stroke Scale.
• Patients were aged ≤85 years and primarily admitted to an endovascular-capable centre.
• Randomisation was 1:1 using a web-based system.
• The study was an open-label, multicentre, blinded-endpoint, randomised controlled trial conducted at ten comprehensive stroke centres in France.

Further clinical trials are considered necessary to firmly conclude on the safety and efficacy of DTAS for patients with suspected acute ischaemic stroke due to large vessel occlusion.

• The authors note that the small sample size from early stopping limits the precision of effect estimates.
• The conclusion that DTAS was associated with increased symptomatic intracranial haemorrhage without beneficial effect on functional outcome is tempered by the underpowered sample.
• The authors explicitly call for further clinical trials to resolve the question of DTAS safety and efficacy.