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

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Brain Ischemia; Reperfusion Injury; Acute Ischemic Stroke; Large Vessel Occlusion; Endovascular Procedures; Thrombectomy; Ischaemic Stroke; Cooling
• Intervention / Treatment: Device: Non-invasive convective head cooling; Other: Standard of Care (SOC)

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.

• Study Type: Interventional
• Enrollment (Estimated): 182
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Davina J McAllister, DipNursing; Phone Number: +64274891940; Email: davina.mcallister@tewhatuora.govt.nz

Study Locations

• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1023
      • Health New Zealand - Auckland
      • Contact: Davina J McAllister, DipNursing; Phone Number: 0274891940; Email: davina.mcallister@tewhatuora.govt.nz
      • Contact: Jessica Wiles, BHSc - Nursing; Email: jessica.wiles@TeWhatuOra.govt.nz
      • Principal Investigator: Doug Campbell, MBChB
      • Sub-Investigator: Brandon Lucke-Wold, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-invasive Convective Head Cooling + Standard of Care; Participants receive non-invasive convective head cooling in addition to standard clinical care for acute anterior circulation ischaemic stroke undergoing endovascular thrombectomy. Head cooling is initiated as early as possible following randomisation and continued throughout interhospital transfer (if applicable), endovascular thrombectomy, and for one hour after reperfusion.	Device: Non-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.
Active Comparator: Standard of Care (SOC) Alone; Participants receive standard clinical care for acute anterior circulation ischaemic stroke undergoing endovascular thrombectomy, without head cooling.	Other: Standard 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 hours after endovascular thrombectomy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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%).	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.	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	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.	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.	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.	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.	First 90 days after endovascular thrombectomy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality	Death from any cause.	90 days after endovascular thrombectomy
Number of Participants with Symptomatic Intracranial Haemorrhage	Symptomatic intracranial haemorrhage defined according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria as a parenchymal haemorrhage type 2 associated with neurological deterioration (increase in NIHSS score ≥4 points) or death.	Within 36 hours after endovascular thrombectomy
Number of Participants with New Arrhythmia and Haemodynamic Compromise	Occurrence of a new cardiac arrhythmia associated with haemodynamic instability requiring clinical intervention.	During the head cooling intervention period, from initiation of cooling to one hour after reperfusion.
Number of Participants with Uncontrolled Hypertension During Head Cooling	Blood pressure >185/110 mmHg or an absolute increase in systolic blood pressure ≥30 mmHg from baseline on two consecutive measurements despite standard pharmacological treatment.	During the head cooling intervention period, from initiation of cooling to one hour after reperfusion.
Number of Participants with Cold-Related Shivering	Clinically significant shivering attributed to head cooling that persists despite systemic warming measures.	During the head cooling intervention period, from initiation of cooling to one hour after reperfusion.
Number of Participants with Pneumonia	Pneumonia diagnosed according to Centers for Disease Control and Prevention criteria.	Within 7 days after stroke or hospital discharge, whichever occurs first
Number of Participants with Local Pressure or Cold-Related Skin Injury	Any local skin injury attributed to pressure or cold exposure from the head cooling device.	From initiation of head cooling through hospital discharge, up to a maximum of 7 days
Number of Participants with Angiographic Vasospasm Requiring Treatment	Angiographic vasospasm occurring during endovascular thrombectomy requiring administration of intra-arterial vasodilators.	During endovascular thrombectomy procedure
Intra-Procedural Complications	Composite outcome including target vessel dissection, vessel perforation, intracranial haemorrhage, or access site haematoma occurring during or immediately following the EVT procedure.	During endovascular thrombectomy procedure

Collaborators and Investigators

• Sponsor: Auckland City Hospital
• Collaborators: Health New Zealand; Neurological Foundation of New Zealand
• Investigators: Principal Investigator: William Diprose, MBChB, University of Auckland, New Zealand; Principal Investigator: Alan Barber, PhD, University of Auckland, New Zealand; Principal Investigator: Doug Campbell, MBChB, Auckland City Hospital

Publications and helpful links

General Publications

• Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18.
• van der Worp HB, Sena ES, Donnan GA, Howells DW, Macleod MR. Hypothermia in animal models of acute ischaemic stroke: a systematic review and meta-analysis. Brain. 2007 Dec;130(Pt 12):3063-74. doi: 10.1093/brain/awm083. Epub 2007 May 3.
• Wang H, Olivero W, Lanzino G, Elkins W, Rose J, Honings D, Rodde M, Burnham J, Wang D. Rapid and selective cerebral hypothermia achieved using a cooling helmet. J Neurosurg. 2004 Feb;100(2):272-7. doi: 10.3171/jns.2004.100.2.0272.
• Rinkel LA, Ospel JM, Brown SB, Campbell BCV, Dippel DWJ, Demchuk AM, Majoie CBLM, Mitchell PJ, Bracard S, Guillemin F, Jovin TG, Muir KW, White P, Saver JL, Hill MD, Goyal M; HERMES Collaborators. What Is a Meaningful Difference When Using Infarct Volume as the Primary Outcome?: Results From the HERMES Database. Stroke. 2024 Apr;55(4):866-873. doi: 10.1161/STROKEAHA.123.044353. Epub 2024 Mar 5.
• Jabonero V, Martinez R, Marin Giron F, Jabonero RM. [Studies on synapses of the peripheral vegetative nervous system. V. Additional observations on the ending systems of postganglionic nerve fibers]. Z Mikrosk Anat Forsch. 1965;73(1):96-116. No abstract available. German.
• Diprose WK, Wang MTM, Campbell D, Sutcliffe JA, McFetridge A, Chiou D, Lai J, Barber PA. Intravenous Propofol Versus Volatile Anesthetics For Stroke Endovascular Thrombectomy. J Neurosurg Anesthesiol. 2021 Jan;33(1):39-43. doi: 10.1097/ANA.0000000000000639.
• Svensson B. [The prevalence of rheumatoid arthritis is lower than previously known]. Lakartidningen. 1989 Jan 4;86(1-2):45-6. No abstract available. Swedish.

Study record dates

Study Major Dates

• Study Start (Estimated): April 10, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: March 29, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Therapeutic hypothermia; Neuroprotection; Endovascular thrombectomy; Penumbra; Head cooling; Selective brain cooling
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemic Stroke; Stroke; Brain Ischemia; Reperfusion Injury; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: COOLHEAD-2B; A+10418 (Other Identifier: Health New Zealand - Auckland)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared outside the study team. This trial involves detailed clinical, imaging, and procedural data collected within a relatively small and geographically defined population, which increases the risk of participant re-identification despite de-identification. In addition, no consent for broader data sharing beyond the study investigators was obtained from participants or their representatives. Access to the final dataset will therefore be restricted to the study investigators for the purposes of scientific analysis and publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No