Periodic Reporting for period 6 - CUCUMBER (Bringing to market the world’s first integrated medical cooling system for minimizing brain damage in stroke patients.)
Période du rapport: 2023-06-01 au 2023-11-30
COTTIS-1 shows that combining intra-ischemic hypothermia by RhinoChill during and after recanalization with mechanical thrombectomy and subsequent surface cooling was feasible in sedated and ventilated patents without symptomatic complications. This hypothermia approach was associated with a substantial salvation of tissue at-risk before recanalization and a very good short- and long-term outcome after three months, with good or complete neurological function. Manuscript reporting the results has now been submitted to the journal STROKE in 1/2023.
The project is now entering the final phase, in which the effect of this procedure will be evaluated in the randomized COTTIS-2 trial. At the Congress NeuroRad on October 13, 2022, very convincing results from an initial study called COTTIS-1 were presented. The clinical study was stopped after 22 patients in consultation with the German Medicines Agency as the primary objectives of the study had already been met.
An ethics application to be able to carry out a more comprehensive study (COTTIS-2) based on the results of the COTTIS-1 trial has now been submitted in 1/2023 and will be likely received by end of Q1. COTTIS-2 will enroll 400 patients, aiming to show a statistically significant difference of 14% or more in survival with good neurological function. In the study, cooling treatment with BrainCool's products combined with thrombectomy will be compared with today's standard treatment. A first interim review of the results will take place already after the inclusion of 100 patients, when the input from the first study shows a significantly greater improvement than 14%. A positive outcome of the study will be the basis for market registration of cooling treatment as a medical indication, i.e. an improved stroke survival with preserved neurological function.
The project is now entering the final phase, in which the effect of this procedure will be evaluated in the randomized COTTIS-2 trial. At the Congress NeuroRad on October 13, 2022, very convincing results from an initial study called COTTIS-1 were presented. The clinical study was stopped after 22 patients in consultation with the German Medicines Agency as the primary objectives of the study had already been met.
An ethics application to be able to carry out a more comprehensive study (COTTIS-2) based on the results of the COTTIS-1 trial has now been submitted in 1/2023 and will be likely received by end of Q1. COTTIS-2 will enroll 400 patients, aiming to show a statistically significant difference of 14% or more in survival with good neurological function. In the study, cooling treatment with BrainCool's products combined with thrombectomy will be compared with today's standard treatment. A first interim review of the results will take place already after the inclusion of 100 patients, when the input from the first study shows a significantly greater improvement than 14%. A positive outcome of the study will be the basis for market registration of cooling treatment as a medical indication, i.e. an improved stroke survival with preserved neurological function.
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.