Combination of Hypothermia and Thrombectomy in Acute Stroke — COTTIS-2  

Ischemic Stroke Clinical Trial

Official title: Combination of Targeted Temperature Management and Thrombectomy After Acute Ischemic Stroke (COTTIS-2) - a Randomised Controlled Study

Status Not yet recruiting

Clinical Trial 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.

Clinical Trial Description

Despite the well-established benefit of endovascular treatment (EVT) for acute ischemic stroke due to large vessel occlusion (LVO), more than half of patients treated with EVT remain functionally dependent despite high reperfusion rates. Thus, new strategies such as additional neuroprotection using hypothermia need to be explored, first to bridge time to reperfusion and second, to attenuate reperfusion injury.

Although therapeutic hypothermia has consistently demonstrated robust neuroprotection in animal ischemic-reperfusion models, randomized trials in acute stroke patients have failed to demonstrate the efficacy of induced hypothermia. The reasons for this treatment failure are diverse and include treatment delay, the unfeasibility of inducing and maintaining hypothermia due to intolerance and shivering in awake patients, the missing recanalization in a large proportion of patients, the heterogeneity of patients included, and too deep (32-34°C) hypothermia associated with an increase in side effects.

In the pilot study COTTIS-1, we could demonstrate the feasibility and safety of immediately induced intraischemic hypothermia to 35°C with non-invasive transnasal cooling by RhinoChill® (BrainCool) followed by surface cooling for 6h after recanalization in sedated and intubated patients with LVO undergoing EVT. By combining this cooling technique with thrombectomy we have tried to address the above mentioned reasons for hypothermia failure. In COTTIS-1, the target temperature of 35°C was reached within 30 min, corresponding to a cooling rate of 2.6°C/h. All patients reached the target temperature, and 86% of the patients had reached ≤35°C at recanalization by thrombectomy. 68% of patients had a good outcome (independency) after 3 months. There were only asymptomatic side effects during hypothermia.

As a consequence, the present COTTIS-2 study is planned to evaluate the efficiency of this cooling protocol in a multicentric, randomized, controlled, end-point-blinded study in Germany. ;

Related Conditions & MeSH terms

• Endovascular Treatment
• Ischemic Stroke
• Large Vessel Occlusion
• Stroke

• NCT number: NCT06301412
• Study type: Interventional
• Source: University of Freiburg
• Contact: Juergen Bardutzky, Prof.
• Phone: +49-15237729739
• Email: juergen.bardutzky@uniklinik-freiburg.de
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 18, 2024
• Completion date: June 18, 2026