Head Cooling in Ischaemic Stroke Patients Undergoing Endovascular Thrombectomy (COOLHEAD-2b)

Head Cooling in Ischaemic Stroke Patients Undergoing Endovascular Thrombectomy: A Phase 2 Randomised Controlled Trial (COOLHEAD-2b)

COOLHEAD-2b is a multicentre, phase 2, prospective, randomised, controlled, open-label, blinded-endpoint trial evaluating the safety and efficacy of non-invasive convective head cooling as an adjunct to endovascular thrombectomy (EVT) in patients with acute anterior circulation ischaemic stroke. Head cooling is initiated as early as possible, including during inter-hospital transfer, and continued until one hour after reperfusion. The primary efficacy endpoint is final infarct volume at 24 hours.

Despite advances in reperfusion therapy, a substantial proportion of patients undergoing EVT for acute ischaemic stroke experience poor functional outcomes, particularly those with delayed reperfusion due to interhospital transfer. Therapeutic hypothermia is a potent neuroprotective intervention in preclinical stroke models but has not been successfully translated into clinical practice due to delayed initiation and systemic complications.

Convective head cooling is a non-invasive, portable method capable of selectively reducing brain temperature while minimizing systemic hypothermia. Phase 1 and feasibility studies (COOLHEAD-1 and COOLHEAD-2a) demonstrated that this approach is safe, well-tolerated, and feasible in patients undergoing EVT.

COOLHEAD-2b will test whether convective head cooling reduces infarct volume and improves clinical outcomes when applied early and continued throughout the EVT workflow, including interhospital transfer. Participants will be randomised 1:1 to head cooling plus standard care or standard care alone. Outcome assessors and imaging core laboratory staff will be blinded to treatment allocation.

All outcome measures are derived from prospectively collected clinical, imaging, and procedural data. Imaging outcomes are assessed by a blinded core laboratory using standardized methods. Functional outcome assessments are performed by trained assessors blinded to treatment allocation. Safety outcomes are actively monitored throughout the peri-procedural and post-procedural periods.

Inclusion Criteria:

• Acute anterior circulation ischaemic stroke planned for endovascular thrombectomy
• Age ≥18 years

Exclusion Criteria:

• Pre-stroke modified Rankin Scale score >2
• Core body temperature <35°C at admission
• Uncontrolled hypertension (≥185/110 mmHg despite treatment in IVT-eligible patients)
• Known contraindications to hypothermia (e.g., haemodynamic instability, symptomatic bradyarrhythmia, cryoglobulinaemia, sickle cell disease, cold agglutinins)
• Vasospastic disorders (e.g., Raynaud's phenomenon)
• Skin lesions preventing secure application of the cooling cap
• Inability to participate in 90-day follow-up