Combination of Hypothermia and Thrombectomy in Acute Stroke

NCT06301412 | Recruiting Phase 3 DMC

• 1 other identifier: COTTIS-2_Version4.0-13Nov23
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test the combination of hypothermia and endovascular treatment in acute stroke patients with large vessel occlusion. The main question it aims to answer is: does an additional cooling to 35°C result in a benefit on clinical outcome ? Participants receive immediate cooling using a noninvasive transnasal cooling technique (RhonoChill) and are maintained at 35°C for 6 hours after reopening of the vessel using surface cooling, and then slowly rewarmed. Researchers will compare the intervention group (hypothermia and endovascular treatment and best medical treatment including iv thrombolysis) and control group (only endovascular treatment and best medical treatment including iv thrombolysis) to see if additional hypothermia leads to a better outcome after 3 months without relevant complications.

Conditions

Ischemic Stroke; Large Vessel Occlusion; Endovascular Treatment

Keywords

hypothermia; neuroprotection

Outcome Measures

Primary Outcomes (1)

• functional outcome

  The presence of patients with good neurological outcome after 3 months as defined by modified Rankin Scale (mRS; on which scores range from 0 to 6, with 0 means no symptoms and 6 means death) of 0-2 or back to baseline before stroke

  3 months

Secondary Outcomes (13)

• infarction volume

  24 hours

• increase in infarction

  24 hours

• recanalization result

  after thrombectomy and 24 hours

• neurological improvement

  48 hours

• outcome at discharge

  up to 3 months

Other Outcomes (2)

• Occurrence of intracerebral haemorrhage (ICH)

  24 hours

• Complications associated with hypothermia

  24hours

Study Arms (2)

EVT group

NO INTERVENTION

standard endovascular treatment (EVT) for large vessel occlusion (LVO) without hypothermia

EVT group plus hypothermia group

ACTIVE COMPARATOR

standard endovascular treatment (EVT) for large vessel occlusion (LVO) combined with hypothermia

Device: hypothermia

Interventions

hypothermia DEVICE

hypothermia is started after intubation for endovascular treatment and induced by transnasal cooling (RhinoChill) to a target temperature of 35°C and hypothermia is then maintained at 35°C for 6 hours after recanalisation by surface cooling followed by slow rewarming by 0.2°C per hour to 36.5°C

EVT group plus hypothermia group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pre-stroke modified Rankin Scale (mRS) 0-2 \[7-point scale rating from 0 (no symptoms) to 6 (dead)\]
• Acute ischemic stroke with NIHSS \>5
• Intracranial occlusion of the M1 or M2 segment of the middle cerebral artery (MCA) or internal carotid artery (ICA) or tandem occlusion on CT-angiography or MR-angiography with indication for endovascular treatment:
• Time window 0-24h:
• Last seen normal to groin puncture \< 6h: native CT or MRI-DWI with ASPECTS \>5
• Last seen normal to groin puncture 6-24h or unknown time window: significant mismatch imaging according to the eligibility criteria of the DEFUSE-3 trial
• Infarct core \<70ml (DWI oder CBF\<30%)
• Penumbra \> 15ml (Tmax \>6sec)
• Ratio penumbra/core \>1.8
• with or without iv thrombolysis with rtPA

You may not qualify if:

• Patients with an intranasal obstruction that prevents complete insertion of the nasal cannula should not be treated with the RhinoChill system.
• Known severe hemorrhagic diathesis (International Normalized Ratio (INR) \>3.0, partial thromboplastin time (PTT) \> 70s, platelet count \< 50.000/μl)
• Brain trauma or neurovascular surgery/intervention \<3 months
• Severe infection
• Pregnant women or women of childbearing potential (women of childbearing potential with negative pregnancy test may be included)
• Known cerebral vasculitis
• Proof of bleeding in cerebral CT or MRI (cerebral microbleeds in MRI \[hypertensive or in the context of cerebral amyloid angiopathy\] is permitted).
• Known life expectancy \< 6 months

Sponsors & Collaborators

• University of Freiburg: lead
• European Union: collaborator
• E+E CRO consulting, Vienna, Austria: collaborator
• Center for Medical data science, University of Vienna, Austria: collaborator

Study Sites (1)

University of Freiburg, Department of Neurology

Freiburg im Breisgau, 79106, Germany

RECRUITING

Related Links

• Results of the pilot study COTTIS-1 on feasibility and safety

MeSH Terms

Conditions

Ischemic Stroke; Hypothermia

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Juergen Bardutzky, Prof.

  University of Freiburg, Department of Neurology, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juergen Bardutzky, Prof.

CONTACT

+49-15237729739; juergen.bardutzky@uniklinik-freiburg.de

Wolf-Dirk Niesen, PD Dr.

CONTACT

0049-761-270-53050; wolf-dirk.niesen@uniklinik-freiburg.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. Juergen Bardutzky

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: March 8, 2024
• Study Start: July 7, 2024
• Primary Completion: March 18, 2026
• Study Completion (Estimated): June 18, 2026
• Last Updated: January 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 6 months to 36 months after publication of the study
• Access Criteria: upon request of scientists with methodologically meaningful evaluation proposal approved by a committee specifically appointed for this evaluation proposal

Locations

DE (1)