Acute Ischemic Stroke, Brain Ischemia, Cooling, Endovascular Procedures, Ischaemic Stroke, Large Vessel Occlusion, Reperfusion Injury, Stroke, Thrombectomy
Conditions
Keywords
Head cooling, Selective brain cooling, Endovascular thrombectomy, Therapeutic hypothermia, Penumbra, Neuroprotection
Brief summary
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.
Detailed description
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.
Interventions
DEVICENon-invasive convective head cooling
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.
OTHERStandard of Care (SOC)
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.
Sponsors
Auckland City Hospital
Neurological Foundation of New Zealand
Health New Zealand
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Intervention model description
This is a randomized, controlled trial evaluating a non-pharmacological device intervention (non-invasive convective head cooling) as an adjunct to standard endovascular thrombectomy care."
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Final Infarct Volume | 24 hours after endovascular thrombectomy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infarct growth | Baseline imaging to 24 hours after endovascular thrombectomy | 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%). |
| Penumbral salvage index | Baseline imaging to 24 hours after endovascular thrombectomy | 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. |
| Early neurological improvement | Baseline to 24 hours after endovascular thrombectomy | 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 |
| Modified Rankin Scale (mRS) score | 90 days after endovascular thrombectomy | 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. |
| Proportion of Participants with Functional Independence | 90 days after endovascular thrombectomy | Proportion of participants achieving functional independence, defined as a modified Rankin Scale (mRS) score of 0 to 2, where lower scores indicate less disability. |
| Proportion of Participants with Excellent Functional Outcome | 90 Days post endovascular thrombectomy | 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. |
| Days Alive and Out of Hospital (DAOH-90) | First 90 days after endovascular thrombectomy | Number of days participants are alive and not admitted to hospital during the first 90 days after endovascular thrombectomy. |
Countries
New Zealand
Contacts
CONTACTDavina J McAllister, DipNursing
PRINCIPAL_INVESTIGATORWilliam Diprose, MBChB
University of Auckland, New Zealand
PRINCIPAL_INVESTIGATORAlan Barber, PhD
University of Auckland, New Zealand
PRINCIPAL_INVESTIGATORDoug Campbell, MBChB
Auckland City Hospital
Outcome results
None listed