Evaluation of Rocuronium Bromide, Sugammadex, and Suxamethonium Chloride in Reducing Post-Intubation Morbidity in Adult Respiratory Distress

The primary objective of this study is to estimate the effect of a combined strategy integrating **rocuronium**, bag face-mask ventilation before intubation, and GEB as an aid for tracheal intubation on early post-intubation related complications in adult patients requiring out-of-hospital emergency tracheal intubation. This is clinically relevant as it aims to improve the safety and effectiveness of emergency tracheal intubation, potentially reducing complications associated with this critical procedure in patients experiencing **respiratory distress**.

Secondary objectives include estimating the effect of the combined strategy on:

• Intubation difficulty
• Out-of-hospital care and mortality
• 28-day mortality

The clinical trial focuses on adult patients experiencing **respiratory distress** who require emergency endotracheal intubation outside of a hospital setting. The study population includes both male and female participants aged 18 years and older. Participants are selected based on the presence of vital distress necessitating emergency intubation, excluding those in cardiac arrest. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the trial data. The selection criteria ensure that the study population is representative of adults in critical need of emergency airway management, with conditions such as trauma, dyspnea, coma, overdoses, and shock being included.

The clinical trial is designed as a **superiority cluster randomized controlled trial** to evaluate the effectiveness of an optimization strategy for emergency tracheal intubation on post-intubation morbidity in adult patients experiencing **respiratory distress**. The trial will involve the administration of **rocuronium bromide**, **sugammadex**, and **suxamethonium chloride**, all delivered via intravenous use. The trial is expected to commence on January 14, 2023, and conclude by October 14, 2025, with a maximum treatment period of one day for each participant.

Participants will be screened based on specific inclusion criteria, which require them to be adults (≥18 years) presenting with vital distress necessitating emergency endotracheal intubation, excluding those in cardiac arrest. The primary endpoint is the proportion of patients experiencing severe intubation-related complications within the first hour post-intubation, including cardiac arrest, arterial hypotension, hypoxemia, severe cardiac arrhythmia, pulmonary aspiration, esophageal intubation, and unintentional extubation. Secondary endpoints focus on the difficulty of the intubation process, out-of-hospital care metrics, and mortality at 28 days.

The trial will include an initial screening visit to confirm eligibility, followed by the intervention phase where the optimization strategy is applied. Follow-up visits will be conducted to monitor for any complications and assess the primary and secondary endpoints. The end-of-study visit will occur at the conclusion of the participant's involvement, which is anticipated to last no more than one day. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or withdrawal of consent by the participant.

The clinical trial involves the administration of **Rocuronium Viatris 10 mg/mL**, a solution for injection/infusion. The active substance in this experimental medication is **rocuronium bromide**, a chemical compound classified under the ATC code M03AC09. The pharmaceutical form is a solution for injection or infusion, and it is administered intravenously. The maximum daily and total dose is 10 mg/mL, with a treatment period limited to one day. This medication is not a pediatric formulation and is not classified as an orphan drug. The product is manufactured by Viatris Sante and is authorized for use in France.

Another experimental medication used in the trial is **Sugammadex Juta Pharma 100 mg/mL**, a solution for injection. The active substance is **sugammadex**, also a chemical compound, with an ATC classification of V03AB35. This medication is administered intravenously, with a maximum daily and total dose of 100 mg/mL, and a treatment period of one day. It is not formulated for pediatric use and is not designated as an orphan drug. The manufacturer is Juta Pharma GmbH, and the product is authorized in France.

The trial also includes the use of **Celocurine 50 mg/mL**, a solution for injection, containing the active substance **suxamethonium chloride**. This chemical compound is classified under the ATC code M03AB01. The medication is administered intravenously, with a maximum daily and total dose of 1 mg/kg, and a treatment period of one day. It is not a pediatric formulation and is not classified as an orphan drug. The product is manufactured by Neuraxpharm France and is authorized for use in France.

All medications are administered intravenously, and participant compliance is monitored throughout the trial. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The focus is on evaluating the effectiveness of these medications in optimizing emergency tracheal intubation and reducing post-intubation morbidity.

Efficacy in the clinical trial titled "Effectiveness of an Optimisation Strategy for Emergency Tracheal Intubation on postintubation Morbidity: A superiority cluster randomised controlled trial - OSETIM" will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the proportion of patients experiencing severe intubation-related complications within the first hour post-intubation. These complications include **cardiac arrest**, arterial hypotension (systolic blood pressure <90 mmHg), hypoxemia (oxygen saturation <90%), severe cardiac arrhythmia such as ventricular tachycardia, pulmonary aspiration, esophageal intubation, and unintentional extubation.

Secondary endpoints will evaluate the difficulty of the intubation process and out-of-hospital care. The Intubation Difficulty Score will be used, with a score >5 indicating difficult intubation. The Copenhagen score will assess intubation conditions as poor, good, or excellent. The trial will also measure the proportion of patients intubated using alternative techniques, the mean number of intubation attempts and failures under direct laryngoscopy, and the mean time of out-of-hospital care. Additionally, the mean total amounts of sedative drugs and vasopressors used post-intubation will be recorded, along with out-of-hospital mortality rates. Mortality at 28 days will be tracked using the French Register of deceased persons.