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| ID | Type | Description | Link |
|---|---|---|---|
| A+10418 | Other Identifier | Health New Zealand - Auckland |
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| Name | Class |
|---|---|
| Neurological Foundation of New Zealand | UNKNOWN |
| Health New Zealand | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Non-invasive Convective Head Cooling + Standard of Care | Experimental | 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. |
|
| Standard of Care (SOC) Alone | Active Comparator | Participants receive standard clinical care for acute anterior circulation ischaemic stroke undergoing endovascular thrombectomy, without head cooling. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Non-invasive convective head cooling | Device | 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. |
| 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 |
| 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 |
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Davina J McAllister, DipNursing | Contact | +64274891940 | davina.mcallister@tewhatuora.govt.nz |
| Name | Affiliation | Role |
|---|---|---|
| William Diprose, MBChB | University of Auckland, New Zealand | Principal Investigator |
| Alan Barber, PhD | University of Auckland, New Zealand | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Health New Zealand - Auckland | Grafton | Auckland | 1023 | New Zealand |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38440891 | Background | 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. | |
| 4161451 |
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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.
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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."
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| 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. |
|
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 |
| 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 |
| Doug Campbell, MBChB |
| Auckland City Hospital |
| Principal Investigator |
| Background |
| 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. |
| 15086235 | Background | 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. |
| 31453877 | Background | 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. |
| 2783474 | Background | 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. |
| 17478443 | Background | 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. |
| 26898852 | Background | 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. |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D000083242 | Ischemic Stroke |
| D002545 | Brain Ischemia |
| D015427 | Reperfusion Injury |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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