Braincool (BRAIN) Study update summary

PRINCESS 2 study overview

• PRINCESS 2 is a multicenter RCT investigating early brain cooling in out-of-hospital cardiac arrest using the RhinoChill device, aiming for neuroprotection by starting cooling during CPR, before hospital arrival.

• The study targets a core temperature of 33°C, with patients randomized during ischemia, contrasting with previous studies that initiated cooling hours later.

• Prior PRINCESS 1 results showed a notable improvement in complete neurological recovery (CPC 1) at 90 days in a selected population, prompting the current trial to focus on early intervention in ventricular fibrillation cases.

• Recruitment is ongoing in six countries, with 245 patients enrolled and a goal to complete recruitment by 2028, maintaining strong protocol adherence and effective cooling in the intervention group.

• An interim analysis is planned for December, focusing on safety, harm, and intervention performance, with oversight by an independent data and safety monitoring board.

COTTIS 2 study overview

• COTTIS 2 evaluates early intra-ischemic hypothermia in severe ischemic stroke patients undergoing thrombectomy, using RhinoChill for rapid brain cooling before and during recanalization.

• The protocol involves cooling to 35°C before reperfusion, followed by surface cooling for six hours, aiming to maximize neuroprotection in salvageable brain tissue.

• Inclusion criteria focus on patients with large vessel occlusion and significant salvageable tissue, with primary outcome measured by the modified Rankin Scale at three months.

• Results from the COTTIS 1 feasibility trial showed 68% of cooled patients achieved good outcomes versus 30% in controls, supporting the potential of early hypothermia.

• Recruitment is ongoing at six sites in Germany, with 55 of 400 patients treated so far, and plans to expand to additional European centers and complete enrollment by end of 2027.

Study progress and site activation

• University Hospital Essen joined in Q2 2025, with first patient included after staff changes and training.

• Uni Klinik Osnabrück and University Hospital Tübingen activated in Q1 2026, with Tübingen already enrolling patients.

• Recruitment and training of new staff ongoing at University Hospital Freiburg, the main trial center.