Multicentre, randomised, controlled, assessor-blinded

1:1 AIRCHILL plus standard EVT care versus standard EVT care without active AIRCHILL respiratory cooling.

Intubated LVO patients undergoing EVT

Adults with acute anterior-circulation large-vessel-occlusion stroke undergoing thrombectomy who require general anaesthesia / invasive ventilation for clinical reasons independent of study participation.

90-day ordinal mRS

Blinded analysis of the full modified Rankin Scale distribution, with mortality, dichotomised disability thresholds and health status as key secondary outcomes.

Working Phase-III target for a common odds ratio around 1.35. Final N should be simulated from AIRCHILL Phase-II mRS distributions and the final estimand.

Adults with acute ischaemic stroke due to protocol-defined anterior-circulation LVO, selected for EVT and requiring invasive ventilation/general anaesthesia as part of routine care.

AIRCHILL respiratory cooling initiated after airway control and as early as feasible before or during thrombectomy, then continued through a prespecified early reperfusion period.

Standard anaesthesia, ventilation, EVT and temperature management without active AIRCHILL respiratory cooling.

Treatment-policy estimand for the shift in 90-day mRS attributable to assignment to AIRCHILL strategy, with death retained at the worst disability category and crossover/interruption handled explicitly.

Parallel, not sequential, workflow

Device setup occurs in parallel with anaesthesia and EVT preparation. A prespecified maximum allowed workflow delay should trigger protocol deviation or omission rather than delaying groin puncture/reperfusion.

Reconstruct every exposure

Patient-side gas temperature, absolute humidity, FiO₂, flow, airway pressure, minute ventilation, exposure duration, systemic temperature and rewarming are captured to support dose-response analysis.

Standardised core principles

Prespecify blood-pressure, oxygenation, ventilation and temperature targets and capture anaesthetic agents. Avoid protocol choices that materially differ between study arms except for AIRCHILL.

Protect the dominant treatment effect

Capture puncture-to-reperfusion time, final eTICI score, number of passes, rescue therapy and procedural complications. AIRCHILL benefit cannot be interpreted if EVT performance differs materially between groups.

Central concealed 1:1 randomisation with variable undisclosed blocks.

Site and one or two high-value baseline variables such as time window and baseline imaging severity; final set selected from ST-2 data without over-stratification.

90-day mRS assessor masked to allocation using standard structured interview methods. Imaging core laboratory fully blinded.

Anaesthesia/EVT team cannot be blinded to device assignment. Treatment deviations and reasons are logged contemporaneously.

One Phase-III interim near 50% information for overwhelming efficacy and non-binding futility, with alpha-spending fixed in the final SAP.

Permit nuisance-parameter/sample-size update based on the observed pooled mRS distribution and missingness if prospectively specified.

Current cooling trials such as FOCUS and COOLHEAD-2b are valuable design benchmarks but are powered for much larger effects or imaging endpoints. AIRCHILL should not transfer those effect sizes directly.

Minimum EVT volume, 24/7 research/randomisation capacity, anaesthesia participation, blinded 90-day outcome pathway, imaging-core transfer and AIRCHILL competency.

Screening volume, eligible fraction, randomisation rate, device-start delay, puncture/reperfusion times, protocol interruptions and completeness of core imaging/90-day mRS.

A site that repeatedly delays reperfusion or cannot deliver the planned thermal exposure should be retrained, paused or removed rather than compensated by additional low-quality enrolment.