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Abstract Background Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. Discussion In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

Background Current cardiac arrest guidelines have limited high‐quality scientific evidence to support recommendations for care. The quality of scientific evidence on which guidelines are based may correlate with improved patient outcomes and meaningful survival. We sought to develop a prioritized list of knowledge gaps in resuscitation to assist researchers, policy makers, and funding agencies in their decision‐making process. Methods and Results A 4‐stage modified Delphi method was used with a panel of cardiac arrest experts. Experts addressed the prompt: “What are the top 3 gaps in knowledge involving cardiac arrest care that should be research priorities for National Institutes of Health/American Heart Association funding to have the greatest impact on public health?” Knowledge gaps were identified in the initial round, rated in a second round, and rank ordered in the third round, and they underwent final review and consensus (final round). The outcome was 10 knowledge gaps, with prioritization of the top 3 gaps. A total of 61 gaps, with 19 distinct themes, were identified by participants. The 10 knowledge gaps most likely to affect public health identified by the expert panel included, in order, the following: telecommunicator cardiopulmonary resuscitation, hemodynamic monitoring for goal‐directed resuscitation, reasons why bystanders fail to respond, optimization of postarrest care, out‐of‐hospital cardiac arrest identification and response, individualizing resuscitation strategies, predicting patients at risk, tools for neuroprognostication, optimal airway management, and optimizing educational strategies. Conclusions Ten priorities for cardiac arrest research were identified, but consensus was not reached on the prioritized top 3. Future research should address these gaps to potentially improve resuscitation guideline evidence quality.