Assessment of remifentanil for rapid sequence induction and intubation in patients at risk of pulmonary aspiration of gastric contents compared to rapid-onset paralytic agents: study protocol for a non-inferiority simple blind randomized controlled trial (the REMICRUSH study)

International audienceAbstract Background Rapid-onset paralytic agents are recommended to achieve muscle relaxation and facilitate tracheal intubation during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents. However, opioids are frequently used in this setting. The study’s objective is to demonstrate the non-inferiority of remifentanil compared to rapid-onset paralytic agents, in association with an hypnotic drug, for tracheal intubation in patients undergoing procedure under general anesthesia and at risk of pulmonary aspiration of gastric contents. Methods The REMICRUSH (Remifentanil for Rapid Sequence Induction of Anaesthesia) study is a multicenter, single-blinded, non-inferiority randomized controlled trial comparing remifentanil (3 to 4 μg/kg) with rapid-onset paralytic agents (succinylcholine or rocuronium 1 mg/kg) for rapid sequence induction in 1150 adult surgical patients requiring tracheal intubation during general anesthesia. Enrolment started in October 2019 in 15 French anesthesia units. The expected date of the final follow-up is October 2021. The primary outcome is the proportion of successful tracheal intubation without major complications. A non-inferiority margin of 7% was chosen. Analyses of the intent-to-treat and per-protocol populations are planned. Discussion The REMICRUSH trial protocol has been approved by the ethics committee of The Comité de Protection des Personnes Sud-Ouest et Outre-Mer II and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The REMICRUSH trial is the first randomized controlled trial powered to investigate whether remifentanil with hypnotics is non-inferior to rapid-onset paralytic agents with hypnotic in rapid sequence induction of anesthesia for full stomach patients considering successful tracheal intubation without major complication. Trial registration ClinicalTrials.gov NCT03960801. Registered on May 23, 2019

Interféron gamma-1b pour la prévention de la pneumonie nosocomiale chez les patients en état critique : essai clinique randomisé de phase 2, contrôlé par placebo

International audienceAbstractPurpose: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanicallyventilated patients.Methods: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomlyassigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferongamma-1b (100 μg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome wasa composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 withinterim safety analyses after enrolling 50 and 100 patients.Results: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b,and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41–66) years; 37(33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquiredpneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94–3.29; P = 0.08). Serious adverseevents were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in theplacebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroupof patients with decreased CCL17 response to interferon-gamma treatment.Conclusions: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death onday 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment