Translation from animal studies of novel pharmacological therapies to clinical trials in cardiac arrest: A systematic review

Lind, P. C. and Johannsen, C. M. and Vammen, L. and Magnussen, A. and Andersen, L. W. and Granfeldt, A.

Resuscitation (2021) 158: 258–269

DOI: 10.1016/j.resuscitation.2020.10.028

Abstract

BACKGROUND: There is a lack of new promising therapies to improve the dismal outcomes from cardiac arrest. The objectives of this study were: (1) To identify novel pharmacological therapies investigated in experimental animal studies and (2) to identify pharmacological therapies translated from experimental animal studies to clinical trials. METHODS: PubMed was searched to first identify relevant experimental cardiac arrest animal models published within the last 20 years. Based on this, a list of interventions was created and a second search was performed to identify clinical trials testing one of these interventions. Data extraction was performed using standardised data extraction forms. RESULTS: We identified 415 animal studies testing 190 different pharmacological interventions. The most commonly tested interventions were classified as vasopressors, anaesthetics/gases, or interventions aimed at molecular targets. We found 43 clinical trials testing 26 different interventions identified in the animal studies. Of these, 13 trials reported positive findings and 30 trials reported neutral findings with regards to the primary endpoint. No study showed harm of the intervention. Some interventions tested in human clinical trials, had previously been tested in animal studies without a positive effect on outcomes. A large number of animal studies was performed after publication of a clinical trial. CONCLUSION: Numerous different pharmacological interventions have been tested in experimental animal models. Despite this only a limited number of these interventions have advanced to clinical trials, however several of the clinical trials tested interventions that were first tested in experimental animal models.

Citation

Lind, P. C., Johannsen, C. M., Vammen, L., Magnussen, A., Andersen, L. W., & Granfeldt, A. (2021). Translation from animal studies of novel pharmacological therapies to clinical trials in cardiac arrest: A systematic review. Resuscitation, 158, 258–269. https://doi.org/10.1016/j.resuscitation.2020.10.028 Animal models, Clinical trials, Review, Drugs, Cardiac arrest, Interventions

Keywords

• Animal models
• Clinical trials
• Review
• Drugs
• Cardiac arrest
• Interventions