Periodic Reporting for period 7 - CUCUMBER (Bringing to market the world’s first integrated medical cooling system for minimizing brain damage in stroke patients.)
Reporting period: 2023-12-01 to 2024-05-31
The feasibility of combining intra-ischemic hypothermia using RhinoChill during and after recanalization with mechanical thrombectomy, followed by surface cooling, was demonstrated in sedated and ventilated patients without symptomatic complications in the COTTIS-1 trial. This hypothermia approach significantly salvaged at-risk tissue before recanalization and resulted in excellent short- and long-term outcomes, with many patients achieving good or complete neurological recovery at three months. Results of this study have been submitted for publication to the journal STROKE in January 2023.
Building on the promising findings of COTTIS-1, the project now advances to its final phase with the initiation of the randomized COTTIS-2 trial. Presented at the NeuroRad Congress on October 13, 2022, initial findings from COTTIS-1 were compelling enough to halt the clinical study after 22 patients, following consultation with the German Medicines Agency, as primary objectives had been achieved. An ethics application for the more extensive COTTIS-2 study, based on COTTIS-1 results, was submitted in January 2023 and is expected to be approved by the end of Q1. COTTIS-2 aims to enroll 400 patients to demonstrate a statistically significant difference of at least 14% in survival with good neurological function compared to current standard treatments. The trial will evaluate BrainCool's cooling products combined with thrombectomy against standard treatments, with an interim analysis planned after the inclusion of 100 patients.
Recent milestones include transitioning sponsorship to BRAINCOOL as mandated by the University of Freiberg, protocol amendments submitted to national authorities and the ethics committee, finalization of case report forms, registration of Randomizer, equipment preparation, and presentations to radiologists and anesthetists for COTTIS-2. Additionally, updated EC-certification from TÜV now covers invasive hypothermia systems, the receipt of essential study materials, successful approval for sponsorship changes, and finalization of a manuscript detailing matched pair analysis using University of Freiberg patient data.
Building on the promising findings of COTTIS-1, the project now advances to its final phase with the initiation of the randomized COTTIS-2 trial. Presented at the NeuroRad Congress on October 13, 2022, initial findings from COTTIS-1 were compelling enough to halt the clinical study after 22 patients, following consultation with the German Medicines Agency, as primary objectives had been achieved. An ethics application for the more extensive COTTIS-2 study, based on COTTIS-1 results, was submitted in January 2023 and is expected to be approved by the end of Q1. COTTIS-2 aims to enroll 400 patients to demonstrate a statistically significant difference of at least 14% in survival with good neurological function compared to current standard treatments. The trial will evaluate BrainCool's cooling products combined with thrombectomy against standard treatments, with an interim analysis planned after the inclusion of 100 patients.
Recent milestones include transitioning sponsorship to BRAINCOOL as mandated by the University of Freiberg, protocol amendments submitted to national authorities and the ethics committee, finalization of case report forms, registration of Randomizer, equipment preparation, and presentations to radiologists and anesthetists for COTTIS-2. Additionally, updated EC-certification from TÜV now covers invasive hypothermia systems, the receipt of essential study materials, successful approval for sponsorship changes, and finalization of a manuscript detailing matched pair analysis using University of Freiberg patient data.
We have fulfilled the following objectives during this project so far, See status per WP below:
WP1 ETHICS REQUIREMENTS
• Ethical committee approval submitted for COTTIS-2 trial (a pivotal trial). BrainCool and University of Freiberg will be closely worked with EE CRO during the process.
WP2 FINALIZING TECHNICAL INTEGRATION
• Completed verification of the HW, SW of BrainCool system
• Update the technical documentation
• Completed all tests in notified body (Intertek) for the certification for BrainCool system
WP3 MANUFACTURING OF COOLCONNECT
• Finalizing all verification and validation activities.
• Finalizing all Work Instructions.
• Planning to manufacture additional 12 units following CB certificate
WP4 CLINICAL VALIDATION
• COTTIS-1: 3-months visit of all patients included in the study from 12/21-5/22. Analysis of all results (clinical and radiological parameters, temperature, outcome, complications, laboratory analyses). Writing the draft of the manuscript, review of the manuscript by all authors, submission to Journal STROKE 1/2023.
• An ethics application for the randomized-controlled COTTIS-2 trial to the ethics committee of the University of Freiburg has been prepared and submitted in 1/2023 (Study protocol; information and written informed consent for patient/relatives/independent physician; Case Report Form, financing plan; patient insurance)
WP5 MARKET ACCESS & REGULATORY AFFAIRS
• Finalize the technical file according MDR
• Working closely with NEMKO (3RD party testing house) for CB-certification
• Prepare a breakthrough designation request for the FDA.
WP6 COMMERCIALIZATION & MARKETING
• Up-dated COTTIS-trials-website on IGNITE/DGNI-homepage since 4/2022
• Workshop investigators at IGNITE meeting 6/2022 at the University of Gießen
• Personal visit by Prof. Bardutzky to the participating centers of COTTIS-2 on side
(29.9.-30.9.22: Hospital in Erlangen, Heidelberg, Darmstadt; 11.7.-15.7.22: Hospital in Bielefeld, Minden, Gießen)
• The results of the clinical study of COTTIS-1 were presented on October 13, 2022, at the NeuroRad 2022 scientific meeting in Kassel, German
• Workshop and presentation of the final COTTIS-1 results and of the protocol of the COTTIS-2 study at the IGNITE meeting in Munich on 18.11.2022
WP7 PROJECT MANAGEMENT
• According to plan - Monitor progress of the project towards the project’s objectives, milestones and deliverables have been performed. University of Freiberg and BrainCool organized meetings within the project group
WP1 ETHICS REQUIREMENTS
• Ethical committee approval submitted for COTTIS-2 trial (a pivotal trial). BrainCool and University of Freiberg will be closely worked with EE CRO during the process.
WP2 FINALIZING TECHNICAL INTEGRATION
• Completed verification of the HW, SW of BrainCool system
• Update the technical documentation
• Completed all tests in notified body (Intertek) for the certification for BrainCool system
WP3 MANUFACTURING OF COOLCONNECT
• Finalizing all verification and validation activities.
• Finalizing all Work Instructions.
• Planning to manufacture additional 12 units following CB certificate
WP4 CLINICAL VALIDATION
• COTTIS-1: 3-months visit of all patients included in the study from 12/21-5/22. Analysis of all results (clinical and radiological parameters, temperature, outcome, complications, laboratory analyses). Writing the draft of the manuscript, review of the manuscript by all authors, submission to Journal STROKE 1/2023.
• An ethics application for the randomized-controlled COTTIS-2 trial to the ethics committee of the University of Freiburg has been prepared and submitted in 1/2023 (Study protocol; information and written informed consent for patient/relatives/independent physician; Case Report Form, financing plan; patient insurance)
WP5 MARKET ACCESS & REGULATORY AFFAIRS
• Finalize the technical file according MDR
• Working closely with NEMKO (3RD party testing house) for CB-certification
• Prepare a breakthrough designation request for the FDA.
WP6 COMMERCIALIZATION & MARKETING
• Up-dated COTTIS-trials-website on IGNITE/DGNI-homepage since 4/2022
• Workshop investigators at IGNITE meeting 6/2022 at the University of Gießen
• Personal visit by Prof. Bardutzky to the participating centers of COTTIS-2 on side
(29.9.-30.9.22: Hospital in Erlangen, Heidelberg, Darmstadt; 11.7.-15.7.22: Hospital in Bielefeld, Minden, Gießen)
• The results of the clinical study of COTTIS-1 were presented on October 13, 2022, at the NeuroRad 2022 scientific meeting in Kassel, German
• Workshop and presentation of the final COTTIS-1 results and of the protocol of the COTTIS-2 study at the IGNITE meeting in Munich on 18.11.2022
WP7 PROJECT MANAGEMENT
• According to plan - Monitor progress of the project towards the project’s objectives, milestones and deliverables have been performed. University of Freiberg and BrainCool organized meetings within the project group
Stroke is the most common cause of disability in Europe and was estimated to cost healthcare over €45 billion in 2020, a cost that is expected to increase by nearly 44% until 2040, according to the European stroke organization Stroke Alliance for Europe (SAFE). The COTTIS-1 study confirms the neuroprotective properties of very early hypothermia combined with thrombectomy as 95% of the penumbra tissues were salvaged by this approach. 64% of patients are within 0-2 on the mRS scale already at discharge from the hospital (approx. 8-9 days after treatment), and 68% at 3 months. Retrospective studies of treated normothermic patients with thrombectomy at the University Hospital of Freiburg show a result of only 32-42% (mRS 0-2), and metaanalysis of randomized trials reported independency after 3 months (mRS 0-2) of 46%. Health economics data available show the influence of patient’s degree of neurological disability on the overall costs that will be incurred in the following years. Publications show that the mean 5-year cumulative costs differed significantly according to the 3-month mRS score; the costs for a 3-month mRS score of 0 or 5 were $53,578 and $257,486 USD, respectively. Three-month mRS score was an independent determinant of long-term costs after stroke. Therefore, it is expected that RhinoChill can significantly reduce the cost of stroke for patients and society.