CIP · development draft v0.1

AIRCHILL-CA Clinical Investigation Plan

Operational development CIP for a staged multicentre randomised investigation of very early respiratory cooling after OHCA. Final regulatory use requires sponsor approval, jurisdiction-specific consent language, locked device configuration and authority/ethics feedback.

1. Administrative information

Sponsor: to be designated. Protocol: AIRCHILL-CA. Device: AIRCHILL investigational transport-ventilation and respiratory-cooling system. Version: development v0.1. Clinical phase: staged feasibility → signal finding → confirmatory efficacy.

2. Rationale and objective

The programme is designed to test whether a substantially earlier respiratory cooling route, added to guideline-based post-resuscitation care, improves neurological outcome without compromising ventilation or cardiovascular stability. It is distinct from trials of delayed systemic hypothermia.

3. Design

Prospective, multicentre, randomised, controlled, open-treatment, blinded-endpoint investigation. Central 1:1 allocation. Phase CA-1 and CA-2 inform the final CA-3 population, dose, timing and sample size.

4. Population

Adults with OHCA who achieve sustained ROSC, remain unconscious and require invasive ventilation. Initial shockable rhythm is the leading pivotal enrichment candidate, subject to CA-2 data.

Draft inclusion

• Age ≥18 years.
• OHCA with sustained ROSC.
• Unable to follow commands after ROSC and clinically requiring invasive ventilation.
• Randomisation/device initiation within the protocol-defined early window.
• Emergency/deferred consent pathway available.

Draft exclusion

• Obvious non-survivable condition or terminal illness with short life expectancy.
• Severe pre-arrest dependency incompatible with the final efficacy claim.
• Uncontrollable major bleeding or respiratory/hemodynamic instability incompatible with study gas delivery.
• Device-specific contraindication from the current risk-management file.
• Pregnancy where required by risk assessment and local law.

5. Intervention

AIRCHILL is initiated as early as feasible after the airway is secured. The treatment dose is defined by patient-side gas temperature, absolute humidity, FiO₂, flow/minute ventilation, airway pressures and exposure duration. Final operating envelope is selected from bench, animal, airway-safety and early clinical data.

6. Comparator

Guideline-based ventilation, post-resuscitation care and temperature management without active AIRCHILL respiratory cooling. Fever prevention, neuroprognostication and withdrawal-of-life-support procedures must be standardised or tightly documented.

7. Schedule of assessments

Screening; randomisation; device start; every critical treatment timestamp; continuous device/ventilation data; arterial blood gases and haemodynamics at prespecified early windows; hospital arrival; 24 h; 48 h; 72 h; discharge; 30 d; ~90 d primary neurological assessment; optional 6/12-month health-economic follow-up. The shared detailed matrix is maintained in the SoA/CRF package.

8. Outcomes

Primary CA-3: blinded favourable neurological outcome at ~90 days using the final locked mRS/CPC definition. Key secondary: mortality, full mRS, CPC, EQ-5D-5L, ventilator-free days, ICU/hospital stay, cognitive/participation outcome where feasible. Safety: device-related SAE, arrhythmia, hypotension/vasopressor escalation, bronchospasm, ventilation compromise, gas-exchange deterioration, pneumonia, seizures and airway injury signals.

9. Randomisation and blinding

Central concealed 1:1 randomisation with variable undisclosed blocks. Stratification limited to site/network and a small number of high-value prognostic variables. Treating clinicians are unblinded; 90-day assessors, adjudicators and central analysts remain blinded whenever feasible.

10. Sample size

Working CA-3 planning target: approximately 2,300 randomised participants for a +7 percentage-point absolute benefit with 90% power, two-sided α=0.05 and 5% primary-outcome loss. Approximately 1,400 may suffice for +9 pp; ~4,400 may be required for +5 pp. Final N must be recalculated from CA-2 AIRCHILL data and the locked estimand.

11. Statistical principles

Primary analysis is intention-to-treat. The final SAP defines the estimand, adjusted primary model, multiplicity, missing-data handling, intercurrent events, subgroup interactions, blinded nuisance-parameter re-estimation and one formal interim analysis. See AIRCHILL SAP.

12. Safety oversight

An independent DSMB reviews unblinded safety and, for CA-3, the formal interim. Predefined domains include mortality imbalance, unexpected device-related serious harm, ventilation compromise, clinically meaningful excess arrhythmia/hypotension and airway injury. See DSMB Charter.

13. Monitoring and data quality

Risk-based monitoring prioritises eligibility, consent, randomisation, critical treatment timestamps, device configuration, primary outcome, SAE/device deficiencies and protocol deviations. Central monitoring identifies delay, missingness, implausible device data and site drift. See screening & monitoring plan.

14. Safety reporting

AE, SAE, device adverse effects, serious adverse device effects, device deficiencies and unanticipated serious adverse device effects are captured and escalated according to ISO 14155, MDR and applicable national/FDA requirements. See safety reporting plan.

15. Ethics and consent

Because enrolment is time-critical and patients lack capacity, the final CIP must use the legally permitted emergency/deferred-consent or representative-consent pathway for each jurisdiction, with survivor consent when capacity returns.

16. Device accountability

Each site records device serial/configuration, software version, consumables, maintenance status, calibration, deviations, deficiencies and return/disposition. Any design change affecting essential performance requires documented impact assessment before continued enrolment.

17. Go/no-go

CA-2 must show acceptable safety, reproducible early delivery, meaningful thermal separation, no material ventilation compromise and a neurological effect estimate supporting a feasible confirmatory N before CA-3 proceeds.

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