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

Lind, P; Johannsen, Cecilie Munch; Vammen, Lauge; Magnussen, Andreas; Andersen, Lars W.; Granfeldt, Asger

doi:10.1016/j.resuscitation.2020.10.028

Cited by 17 publications

(16 citation statements)

References 74 publications

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“… 9 Another recent systematic review reported the rate of translation from animal models to human trials for therapies targeted at cardiac arrest. 8 Though again, this review did not have a specific focus on functional neurologic outcome. While the review published by Lind et al identified the large number of experimental therapies targeted at postcardiac arrest physiology, the authors noted a relative dearth of clinical trials investigating those same therapies in humans.…”

Section: Introductionmentioning

confidence: 99%

“…9 Another recent systematic review reported the rate of translation from animal models to human trials for therapies targeted at cardiac arrest. 8 8 Additionally, the review published in 2021 did not compare the effects of different pharmacologic agents. 8 The review proposed here seeks to compile the best available evidence for pharmacologic interventions that will improve functional neurologic outcomes in humans following cardiac arrest and compare this directly to current practice guidelines.…”

Section: Introductionmentioning

confidence: 99%

“… 2 6 8 9 Several novel compounds have been investigated in animal studies, with some notation of effect on neurologic function, though only a small minority have made the transition from animal models into human trials. 8 The review proposed here will focus on identifying the best available data from human studies and report on therapies that may not have been explicitly mentioned in international guidelines to date.…”

Section: Introductionmentioning

confidence: 99%

“…While the review published by Lind et al identified the large number of experimental therapies targeted at postcardiac arrest physiology, the authors noted a relative dearth of clinical trials investigating those same therapies in humans. 8 Additionally, the review published in 2021 did not compare the effects of different pharmacologic agents. 8 The review proposed here seeks to compile the best available evidence for pharmacologic interventions that will improve functional neurologic outcomes in humans following cardiac arrest and compare this directly to current practice guidelines.…”

Section: Introductionmentioning

confidence: 99%

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Review of novel therapeutics in cardiac arrest (ReNTICA): systematic review protocol

et al. 2022

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IntroductionCardiac arrest remains a common and devastating cause of death and disability worldwide. While targeted temperature management has become standard of care to improve functional neurologic outcome, few pharmacologic interventions have shown similar promise.Methods/analysisThis systematic review will focus on prospective human studies from 2015 to 2020 available in PubMed, Web of Science and EMBASE with a primary focus on impact on functional neurologic outcome. Prospective studies that include pharmacologic agents given during or after cardiac arrest will be included. Study selection will be in keeping with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. If sufficient data involving a given agent are available, a meta-analysis will be conducted and compared with current evidence for therapies recommended in international practice guidelines.Ethics and disseminationFormal ethical approval will not be required as primary data will not be collected. The results will be disseminated through peer-reviewed publication, conference presentation and lay press.PROSPERO registration numberInternational Prospective Register for Systematic Reviews (CRD42021230216).

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Review of novel therapeutics in cardiac arrest (ReNTICA): systematic review protocol

et al. 2022

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“… 6 Despite this, only a minority of pre‐clinically tested pharmacological interventions actually advance to clinical testing and experimental positive results often translate unsuccesfully. 7 If the quality of results from preclinical studies could be improved, this could increase the likelihood of translation of positive results to clinical trials. Conducting high quality, clinically relevant experimental animal research is therefore of key importance.…”

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confidence: 99%

Cardiac Arrest in Pigs With 48 hours of Post‐Resuscitation Care Induced by 2 Methods of Myocardial Infarction: A Methodological Description

Vammen

Johannsen

Magnussen

et al. 2021

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Background Systematic reviews have disclosed a lack of clinically relevant cardiac arrest animal models. The aim of this study was to develop a cardiac arrest model in pigs encompassing relevant cardiac arrest characteristics and clinically relevant post‐resuscitation care. Methods and Results We used 2 methods of myocardial infarction in conjunction with cardiac arrest. One group (n=7) had a continuous coronary occlusion, while another group (n=11) underwent balloon‐deflation during arrest and resuscitation with re‐inflation after return of spontaneous circulation. A sham group was included (n=6). All groups underwent 48 hours of intensive care including 24 hours of targeted temperature management. Pigs underwent invasive hemodynamic monitoring. Left ventricular function was assessed by pressure‐volume measurements. The proportion of pigs with return of spontaneous circulation was 43% in the continuous infarction group and 64% in the deflation‐reinflation group. In the continuous infarction group 29% survived the entire protocol while 55% survived in the deflation‐reinflation group. Both cardiac arrest groups needed vasopressor and inotropic support and pressure‐volume measurements showed cardiac dysfunction. During rewarming, systemic vascular resistance decreased in both cardiac arrest groups. Median [25%;75%] troponin‐I 48 hours after return of spontaneous circulation, was 88 973 ng/L [53 124;99 740] in the continuous infarction group, 19 661 ng/L [10 871;23 209] in the deflation‐reinflation group, and 1973 ng/L [1117;1995] in the sham group. Conclusions This article describes a cardiac arrest pig model with myocardial infarction, targeted temperature management, and clinically relevant post‐cardiac arrest care. We demonstrate 2 methods of inducing myocardial ischemia with cardiac arrest resulting in post‐cardiac arrest organ injury including cardiac dysfunction and cerebral injury.

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Current animal models of extracorporeal cardiopulmonary resuscitation: A scoping review

et al. 2023

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

Cited by 17 publications

References 74 publications

Review of novel therapeutics in cardiac arrest (ReNTICA): systematic review protocol

Review of novel therapeutics in cardiac arrest (ReNTICA): systematic review protocol

Cardiac Arrest in Pigs With 48 hours of Post‐Resuscitation Care Induced by 2 Methods of Myocardial Infarction: A Methodological Description

Current animal models of extracorporeal cardiopulmonary resuscitation: A scoping review

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