Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac Arrest

Argaud, Laurent; Cour, Martin; Dubien, Pierre-Yves; Giraud, François; Jossan, Claire; Riche, Benjamin; Hernu, Romain; Darmon, Michaël; Poncelin, Yves; Tchénio, Xavier; Quenot, Jean‐Pierre; Freysz, M.; Kamga, Cyrille; Beuret, Pascal; Usseglio, Pascal; Badet, Michel; Anette, Bastien; Chaulier, Kevin; Alasan, Emel; Sadoune, Sonia; Bobbia, Xavier; Zéni, Fabrice; Gueugniaud, Pierre‐Yves; Robert, Dominique; Roy, Pascal; Ovize, Michel

doi:10.1001/jamacardio.2016.1701

Cited by 73 publications

(50 citation statements)

References 36 publications

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“…In experimental models of sepsis and/or inflammationinduced acute lung injury, CsA has been consistently reported to improve lung function via mitochondrial processes, including PTP inhibition [7,8]. Even though no clinical trial has been specifically designed to investigate the potential benefits of CsA in ARF, we reported, in a post hoc analysis of the CsA in cardiac arrest resuscitation (CYRUS) trial, that CsA may dramatically limit the severity of post-cardiac arrest ARF, corroborating the abovementioned pre-clinical findings [9,10]. Encouragingly, we also observed, in a predefined ancillary study of the CYRUS trial, significantly higher total and CD4+ lymphocyte counts at 24 h after cardiac arrest in patients treated with CsA than in controls [11].…”

supporting

confidence: 85%

“…Encouragingly, we also observed, in a predefined ancillary study of the CYRUS trial, significantly higher total and CD4+ lymphocyte counts at 24 h after cardiac arrest in patients treated with CsA than in controls [11]. Importantly, no safety concerns, including an increase in nosocomial infections, were reported in trials (in which thousands of patients were included) that have tested short-term off-label CsA use, as it would be the case for COVID-19 [3,[9][10][11][12][13]]. Yet, the toxicity of CsA cannot be excluded at concentrations that may be required to inhibit SARS-CoV-2 [3][4][5][6].…”

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confidence: 53%

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Cyclosporine A: a valid candidate to treat COVID-19 patients with acute respiratory failure?

2020

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented number of hypoxemic pneumoniae since the first cases were diagnosed in China in December 2019. In only a few weeks, tens of thousands of patients have died of acute respiratory failure (ARF) in Europe and then in North America, according to Johns Hopkins University and Medicine Coronavirus Resource Center (https://coronavirus.jhu.edu). Numerous promising antiviral therapies against SARS-CoV-2 are being investigated with the hope of preventing both interindividual transmission and severe complications of the disease [1]. COVID-19-induced ARF is thought to be related to both direct viral pathogenicity and dysregulated inflammatory host response. Unfortunately, current treatment remains only supportive and symptomatic [2]. Therefore, there is an urgent need for effective drugs targeting this life-threatening complication, in particular, for patients developing acute respiratory distress syndrome. The best candidate drug should (1) prevent hyperinflammation-induced lung injury; (2) inactivate viral replication; (3) be widely available; (4) be safe, including when administered with other antivirals; and (5) be affordable. We speculate that cyclosporine A (CsA) might fulfill all these criteria. CsA has been used for decades to prevent organ rejection and to treat T cell-associated autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or interstitial lung disease [3, 4]. CsA exerts its immunosuppressive and anti-inflammatory effects by

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confidence: 85%

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confidence: 53%

Cyclosporine A: a valid candidate to treat COVID-19 patients with acute respiratory failure?

2020

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“…Several studies have shown a significant therapeutic effect by focusing on a particular severity group among all patients if they had not been able to show for all patients [19]. Considering the diversity of the PCAS population, PCAS patients of particular subgroups may benefit more from any treatments such as mild therapeutic hypothermia [20], controlled reperfusion [21,22], and other treatments [23,24], which could not show a significant therapeutic effect for all PCAS patients. Previously, a few studies have attempted to evaluate the effects of therapies for PCAS patients according to the severity by using a single factor such as "time until ROSC" [25], but this may be insufficient for risk classification, because the severity could be influenced by a number of pre-hospital factors.…”

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External validation of a risk classification at the emergency department of post-cardiac arrest syndrome patients undergoing targeted temperature management

et al. 2019

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Introduction: There are no established risk classification for post-cardiac arrest syndrome (PCAS) patients at the Emergency Department (ED) undergoing targeted temperature management (TTM). The aim of this study was to externally validate a simplified version of our prognostic score, the "post-Cardiac Arrest Syndrome for Therapeutic hypothermia score" (revised CAST [rCAST]) and estimate the predictive accuracy of the risk classification based on it. Methods: For the external validation, we used data from an out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM), which is a multicenter, prospective registry of OHCA patients across Japan. Eligible patients were PCAS patients treated with TTM at 33ºC-36ºC between June 2014 and December 2015. We validated the accuracy of rCAST for predicting the neurological outcomes at 30 and 90 days. Results: Among the 12,024 OHCA patients, the data of 460 PCAS patients treated by TTM were eligible for the validation. The areas under the curve of rCAST for predicting the neurological outcomes at 30 and 90 days were 0.892 and 0.895, respectively. The estimated sensitivity and specificity of the risk categories for the outcomes were as follows: 0.95 (95% CI: 0.92-0.98) and 0.47 (0.40-0.55) for the low (rCAST: ≤5.5), 0.62 (0.56-0.68) and 0.48 (0.40-0.55) for the moderate (rCAST: 6.0-14.0), and 0.57 (0.51-0.63) and 0.95 2 (0.91-0.98) for the high severity category (rCAST: ≥14.5). Conclusions: The rCAST was useful for predicting the neurological outcomes with high accuracy in PCAS patients, and the three grades was developed for a risk classification based on the rCAST.

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“…Over the recent years, intense research aiming to limit this phenomenon was performed in order to decrease the risk of brain damage after CA. However, despite encouraging preclinical results, no drug was shown to be efficient in humans (3,4). To date, targeted temperature management (TTM) is the only treatment firmly recommended in comatose patients resuscitated from a CA (5).…”

mentioning

confidence: 99%

Hyperoxia in post-cardiac arrest: friend or foe?

Llitjos

Cariou

2018

J. Thorac. Dis

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Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac Arrest

Abstract: clinicaltrials.gov Identifier: NCT01595958; EudraCT Identifier: 2009-015725-37.

Cited by 73 publications

References 36 publications

Cyclosporine A: a valid candidate to treat COVID-19 patients with acute respiratory failure?

Cyclosporine A: a valid candidate to treat COVID-19 patients with acute respiratory failure?

External validation of a risk classification at the emergency department of post-cardiac arrest syndrome patients undergoing targeted temperature management

Hyperoxia in post-cardiac arrest: friend or foe?

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