Targeted Temperature Management in Acute Ischemic Stroke

Official title

Targeted Temperature Management for Neuroprotection in Acute Ischemic Stroke: A Randomized Controlled Pilot Trial

Overview

The goal of this interventional trial is to evaluate whether the CB240\_Aurora medical device is effective for targeted temperature management in adult patients with acute ischemic stroke. The main questions it aims to answer are: Is the CB240\_Aurora effective in maintaining normothermia in patients with acute ischemic stroke? Does the medical device improve clinical and radiological outcomes? Is the medical device well tolerated by patients? Researchers will compare an interventional arm, in which the CB240\_Aurora measures and treats body temperature to maintain normothermia, with a control arm, in which the CB240\_Aurora only measures but does not treat body temperature. Participants will wear the medical device for 72 consecutive hours in the Stroke Unit. Outcome assessments will be performed at 72 hours, 7 days, and 3 months.

Detailed description

Neuroprotection is a potential therapeutic strategy to complement reperfusion and prevent the progression of cerebral ischemia in patients with acute ischemic stroke. One of the most promising approaches is Targeted Temperature Management (TTM), which involves controlling body temperature to prevent fever, maintain normothermia, or induce hypothermia in order to reduce brain injury and improve clinical outcomes. While hypothermia has demonstrated clinical benefits in patients with cardiac arrest and hypoxic- schemic encephalopathy, no significant evidence currently supports its efficacy in acute stroke. Maintaining normothermia through TTM may offer similar neuroprotective benefits with fewer complications. Current guidelines for patients with intracerebral hemorrhage, subarachnoid hemorrhage, and ischemic stroke recommend maintaining body temperature between 36°C and 37.5°C, ideally using automated control systems.

In this context, Neuron Guard has developed the CB240\_Aurora device, which targets cerebral temperature through the vascular anatomy of the neck to enhance heat exchange. This system has shown potential in stabilizing brain temperature while maintaining systemic normothermia and reducing systemic side effects. Its use could be extended beyond intensive care settings to broader patient populations, both for managing fever episodes and for enhancing neuroprotection.

The experimental treatment with the CB240\_Aurora device is designed as a complementary approach to standard therapies, aiming to improve their effectiveness. The device will continuously monitor body temperature and deliver treatment to maintain normothermia, defined as a temperature ≥36°C and \<37°C at the time of study inclusion.

In the control group, patients will receive care according to the latest ischemic stroke treatment guidelines, including standard temperature management. In this group, the CB240\_Aurora device will be used exclusively for temperature monitoring without providing active treatment.

Interventions

• Device Targeted Temperature Management with CB240_Aurora
  The proposed experimental treatment with the CB240\_Aurora device will serve as a complementary approach to standard therapies, aiming to enhance their effectiveness. The device will continuously monitor body temperature and deliver treatment to maintain normothermia, defined as a temperature ≥36°C and \<37°C at the time of study inclusion.
• Device Standard of care Temperature treatment
  In the control group, patients will receive treatment according to the latest guidelines for the management of ischemic stroke, including standard body temperature management. The CB240\_Aurora device will be used exclusively in monitoring mode, without delivering any active treatment, and will be maintained for 72 consecutive hours from the time of enrollment

Primary outcome measures

• Duration of normothermia maintenance during the first 72 hours [Time frame: T0 (0 hour)T1; ( 72 hours)]

Secondary outcome measures (7)

• Modified Rankin Scale (mRS) [Time frame: T2 (day 7); T3 (day 90)]
• National Institutes of Health Stroke Scale (NIHSS) [Time frame: T2 (day 7); T3 (day 90)]
• Change in the volume of the ischemic lesion measured by MRI [Time frame: T2 (day 7)]
• hemorrhagic transformation of the ischemic lesion at MRI [Time frame: T2 (day 7)]
• Incidence of adverse events (AEs) and severe AEs (SAEs) that are related to treatment. [Time frame: T0 (day 0); T1 (day 3); T2 (day 7); T3( day 90)]
• Number of patients requiring to stop treatment sessions [Time frame: from T0 (day 0); T3 (day 90)]
• Qualitative assessment of device tollerability (QADT) [Time frame: T2 (day 7); T3 (day 90)]

Eligibility criteria

Inclusion criteria

• Age >18 years;
• Both sexes;
• Diagnosis of acute ischemic stroke confirmed by clinical evaluation by a neurologist and neuroimaging (CT or brain MRI);
• Acute ischemic stroke with symptom onset within 48 hours;
• Anterior circulation stroke with evidence on neuroimaging (CT angiography) of occlusion of the middle cerebral artery in segments M1, M2, or M3;
• NIHSS score between 6 and 25;
• First clinical stroke;
• Axillary temperature ≥36°C and <37°C;
• Informed consent obtained for study participation.

Exclusion criteria

• Stroke involving multiple vascular territories;
• Presence of intracerebral hemorrhage;
• Pregnancy;
• Moderate-to-severe or severe pre-stroke disability defined as mRS >3;
• Presence of a cardiac pacemaker or any other conditions contraindicating brain MRI.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• IRCCS Istituto delle Scienze Neurologiche di Bologna - AUSL of Bologna — Bologna

Publications

• Lavinio A, Beqiri E, Kataria K. A Novel Technology for Targeted Brain Temperature Management. Neurocrit Care. 2024 Apr;40(2):785-790. doi: 10.1007/s12028-023-01800-7. Epub 2023 Jul 27. No abstract available. PMID 37498461
• Lavinio A, Andrzejowski J, Antonopoulou I, Coles J, Geoghegan P, Gibson K, Gudibande S, Lopez-Soto C, Mullhi R, Nair P, Pauliah VP, Quinn A, Rasulo F, Ratcliffe A, Reddy U, Rhodes J, Robba C, Wiles M, Williams A. Targeted temperature management in patients with intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic stroke: updated consensus guideline recommendations by the Neuropr PMID 37225535
• Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, Levin H, Ullen S, Rylander C, Wise MP, Oddo M, Cariou A, Belohlavek J, Hovdenes J, Saxena M, Kirkegaard H, Young PJ, Pelosi P, Storm C, Taccone FS, Joannidis M, Callaway C, Eastwood GM, Morgan MPG, Nordberg P, Erlinge D, Nichol AD, Chew MS, Hollenberg J, Thomas M, Bewley J, Sweet K, Grejs AM, Christensen S, Haenggi M, Levis A, Lundin A, During J, Sch PMID 34133859
• 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. PMID 15086235
• Lyden P, Hemmen T, Grotta J, Rapp K, Ernstrom K, Rzesiewicz T, Parker S, Concha M, Hussain S, Agarwal S, Meyer B, Jurf J, Altafullah I, Raman R; Collaborators. Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2). Stroke. 2016 Dec;47(12):2888-2895. doi: 10.1161/STROKEAHA.116.014200. Epub 2016 Nov 10. PMID 27834742
• Lyden PD, Allgren RL, Ng K, Akins P, Meyer B, Al-Sanani F, Lutsep H, Dobak J, Matsubara BS, Zivin J. Intravascular Cooling in the Treatment of Stroke (ICTuS): early clinical experience. J Stroke Cerebrovasc Dis. 2005 May-Jun;14(3):107-14. doi: 10.1016/j.jstrokecerebrovasdis.2005.01.001. PMID 17904009
• You JS, Kim JY, Yenari MA. Therapeutic hypothermia for stroke: Unique challenges at the bedside. Front Neurol. 2022 Oct 3;13:951586. doi: 10.3389/fneur.2022.951586. eCollection 2022. PMID 36262833
• Yenari MA, Han HS. Neuroprotective mechanisms of hypothermia in brain ischaemia. Nat Rev Neurosci. 2012 Feb 22;13(4):267-78. doi: 10.1038/nrn3174. PMID 22353781

Identifiers

NCT: NCT07096687 · TTM-STROKE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗