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

N/ANot Yet RecruitingNCT07526649

Auckland City Hospital182 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

Interventions

Non-invasive convective head coolingDEVICE

Non-invasive convective head cooling delivered using a cooling cap system that circulates chilled fluid around the scalp and neck. Cooling is commenced in the emergency department following randomisation, with a target coolant temperature of -5 °C (adjustable for comfort). Cooling is continued during interhospital transfer (if applicable), during the endovascular thrombectomy procedure, and for one hour following reperfusion. Systemic rewarming measures may be used to maintain core body temperature above 35 °C if required.

Standard of Care (SOC)OTHER

Guideline-based management of acute ischaemic stroke, including endovascular thrombectomy, with supportive medical care as determined by the treating clinical team. No head cooling device is applied.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Final Infarct Volume

Final infarct volume (mL), defined as the manually segmented volume of infarcted brain tissue on 24-hour follow-up CT or MRI brain imaging. Segmentation will be performed by a blinded imaging core laboratory using de-identified imaging files.

Time frame: 24 hours after endovascular thrombectomy

Secondary Outcomes

Infarct growth

Infarct growth, defined as the difference between the final infarct volume on 24-hour follow-up imaging and the baseline infarct core volume estimated using automated CT perfusion software (relative cerebral blood flow \<30%).

Time frame: Baseline imaging to 24 hours after endovascular thrombectomy

Penumbral salvage index

Penumbral salvage index, defined as the proportion of baseline hypoperfused or penumbral brain tissue not progressing to infarction, calculated using baseline CT perfusion imaging and final infarct volume on 24-hour follow-up imaging.

Time frame: Baseline imaging to 24 hours after endovascular thrombectomy

Early neurological improvement

Early neurological improvement, defined as the percentage change in the National Institutes of Health Stroke Scale (NIHSS), a neurological deficit scale ranging from 0 to 42 where higher scores indicate worse neurological impairment, from baseline to 24 hours

Time frame: Baseline to 24 hours after endovascular thrombectomy

Modified Rankin Scale (mRS) score

Degree of disability or dependence in daily activities measured using the modified Rankin Scale (mRS), an ordinal scale ranging from 0 (no symptoms) to 6 (death), where higher scores indicate greater disability. Assessment is performed by a trained, blinded study team member using the Rankin Focused Assessment.

Time frame: 90 days after endovascular thrombectomy

Proportion of Participants with Functional Independence

Proportion of participants achieving functional independence, defined as a modified Rankin Scale (mRS) score of 0 to 2, where lower scores indicate less disability.

Time frame: 90 days after endovascular thrombectomy

Proportion of Participants with Excellent Functional Outcome

Proportion of participants achieving an excellent functional outcome defined as a modified Rankin Scale (mRS) score of 0 to 1, where lower scores indicate minimal or no disability.

Time frame: 90 Days post endovascular thrombectomy

Days Alive and Out of Hospital (DAOH-90)

Number of days participants are alive and not admitted to hospital during the first 90 days after endovascular thrombectomy.

Time frame: First 90 days after endovascular thrombectomy