CIP · development draft v0.1

AIRCHILL-STROKE Clinical Investigation Plan

Operational CIP for peri-EVT AIRCHILL in adults with anterior-circulation LVO who already require general anaesthesia and invasive ventilation. The protocol explicitly prohibits delaying arterial puncture or reperfusion for study treatment.

1. Administrative information

Sponsor: to be designated. Protocol: AIRCHILL-STROKE. Device: AIRCHILL investigational ventilation/cooling system. Version: development v0.1. Stages: ST-1 feasibility → ST-2 signal finding → ST-3 confirmatory.

2. Objective

Determine whether very early respiratory cooling delivered around thrombectomy improves 90-day functional outcome while preserving anaesthesia, haemodynamics and EVT speed/quality.

3. Design

Prospective multicentre randomised controlled open-treatment, blinded-endpoint investigation. Central 1:1 allocation before arterial puncture or at the earliest feasible peri-EVT point.

4. Population

Adults with acute anterior-circulation LVO selected for EVT who require general anaesthesia and invasive ventilation for clinical reasons independent of research participation.

Draft inclusion

• Age ≥18 years.
• Protocol-defined anterior-circulation LVO eligible for EVT.
• General anaesthesia/invasive ventilation clinically indicated.
• Imaging profile within final ASPECTS/core/penumbra criteria.
• Randomisation within the final early/extended time window.
• Permitted consent pathway available.

Draft exclusion

• Primary intracranial haemorrhage.
• Severe pre-stroke disability above the final locked threshold.
• Refractory haemodynamic or respiratory instability incompatible with study gas delivery.
• Terminal illness or clear non-survivable condition.
• Device-specific contraindication.
• Any circumstance in which study procedures would delay reperfusion.

5. Intervention

AIRCHILL begins after airway security and is integrated in parallel with anaesthesia and EVT preparation. Device setup must not extend door-to-puncture or puncture-to-reperfusion intervals. The final dose is defined by patient-side temperature, humidity, FiO₂, flow/minute ventilation, pressures and duration.

6. Comparator

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

7. Schedule of assessments

Screening/imaging; pre-randomisation baseline; randomisation/device start; continuous peri-procedural device and physiological data; puncture; reperfusion; immediate post-EVT; 2–6 h; 24 h imaging/NIHSS; 48–72 h; discharge; 30 d; 90 d blinded mRS/EQ-5D. Shared detailed matrix: SoA / CRF.

8. Endpoints

Primary ST-3: blinded ordinal 90-day mRS shift. Key secondary: mortality, mRS 0–2 and 0–1, NIHSS, EQ-5D-5L, symptomatic ICH, malignant oedema/decompressive surgery, ICU/hospital stay. ST-2 imaging: final infarct volume, infarct growth, penumbral salvage where available, oedema metrics. Procedural: puncture-to-reperfusion, eTICI, passes, rescue treatment. Safety: device-related SAE, ventilation/gas-exchange compromise, haemodynamic events, arrhythmia, pneumonia and any study-attributable EVT delay.

9. Randomisation/blinding

Central concealed 1:1 randomisation, variable blocks, limited stratification by site and key baseline severity/time-window variables. Treating team unblinded; 90-day mRS assessor and imaging core laboratory blinded.

10. Sample size

Working ST-3 anchor: ~1,600 participants for common OR ~1.35. ~1,300 for OR ~1.40; >2,000 may be required for OR ~1.30. Final simulation uses ST-2 AIRCHILL mRS distributions, the final covariates/estimand, missingness and interim design.

11. Statistics

ITT primary analysis using proportional-odds ordinal logistic regression, with prespecified assumption checks and robust sensitivity analysis. Imaging analyses use blinded core-lab continuous endpoints with strategies preventing survivorship bias. See SAP.

12. DSMB and stopping

Independent DSMB reviews respiratory/device safety, haemodynamics, symptomatic ICH, mortality, malignant oedema and any treatment-attributable delay in puncture/reperfusion. Formal ST-3 efficacy/futility interim near 50% information is planned subject to final statistical design. See DSMB Charter.

13. Monitoring

Critical data include eligibility, baseline imaging, consent, randomisation, device configuration/start, arterial puncture/reperfusion timestamps, eTICI, 24-h imaging, SAE/device deficiency and 90-day mRS. Central monitoring flags treatment delays and site-specific workflow drift. See operations plan.

14. Ethics

No participant is intubated solely for AIRCHILL. Consent follows local prospective representative or emergency/deferred pathways, with participant consent if capacity returns.

15. Go/no-go

ST-2 must show acceptable safety, no material EVT delay, reproducible thermal separation, coherent imaging/early neurological signal and a 90-day mRS distribution supporting a feasible pivotal trial.

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