Evaluation of Pre-Emptive Noradrenaline Tartrate Infusion to Mitigate Cardiovascular Collapse in Critically Ill Adults Undergoing Endotracheal Intubation

The primary objective of the PREVENTION Randomized Controlled Trial is to evaluate the efficacy of pre-emptive **vasopressor** therapy in reducing the incidence of cardiovascular collapse, a composite endpoint, in critically ill adults undergoing endotracheal intubation. This is clinically relevant as cardiovascular collapse during intubation can lead to significant morbidity and mortality, and identifying effective preventive strategies is crucial for improving patient outcomes in critical care settings.

The clinical trial involves a study population of **critically ill** adults aged 18 years or older, encompassing both male and female participants. The trial focuses on individuals undergoing in-hospital urgent tracheal intubation due to life-threatening conditions requiring intubation for cardiorespiratory failure or neurological impairment. Participants are expected to receive sedation, with or without neuromuscular blockade, as part of their treatment protocol. The trial population includes a vulnerable group, given the severity of their medical conditions. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria emphasize the necessity for intubation and the involvement of healthcare providers experienced in performing endotracheal intubation within the participating unit.

The clinical trial is designed to evaluate the efficacy of pre-emptive vasopressor therapy in reducing the incidence of cardiovascular collapse among critically ill adults undergoing endotracheal intubation. This study employs a **randomized**, **controlled** trial design, ensuring that participants are randomly assigned to either the intervention group receiving noradrenaline tartrate or a control group. The trial is conducted in a **double-blind** manner, meaning neither the participants nor the healthcare providers are aware of the group assignments, to minimize bias. The trial is expected to span approximately two years, with an estimated recruitment start date of July 1, 2023, and an anticipated end date of July 10, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 years or older), the necessity for urgent tracheal intubation due to **critical illness**, and planned administration of sedation. Follow-up visits will be scheduled to monitor the primary endpoints, which include mean arterial pressure (MAP) below 60 mmHg and cardiac arrest, as well as secondary endpoints like cardiac arrest within 30 minutes from induction and severe hypertension. The end-of-study visit will conclude the participant's involvement, assessing the overall outcomes and any adverse events.

The expected length of participant involvement is determined by the duration of the intervention and follow-up period, which is aligned with the trial's primary and secondary endpoints. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial's methodology and design are structured to ensure robust data collection and analysis, contributing valuable insights into the management of cardiovascular stability during critical care interventions.

The clinical trial involves the administration of **noradrenaline tartrate**, marketed under the name "NORADRENALINA TARTRATO MONICO 2 mg/ml Concentrato per soluzione per infusione." This experimental medication is provided in the form of a **solution for infusion**. The active substance, **noradrenaline tartrate**, is of chemical origin and is classified under the ATC code C01CA03, which corresponds to norepinephrine. The medication is administered via **intravenous infusion**. The dosing regimen specifies a maximum daily dose of 1 mg/kg and a maximum total dose of 10 mg/kg, with a treatment period not exceeding one day. The pharmaceutical product is not a pediatric formulation and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of the experimental medication to evaluate its efficacy in preventing cardiovascular collapse during tracheal intubation in critically ill adults. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol. The trial aims to assess the potential benefits of pre-emptive vasopressor therapy in this clinical setting.

The efficacy of the clinical trial titled "Preventing caRdiovascular collapsE with VasoprEssors duriNg Tracheal IntubatiON: The PREVENTION Randomized Controlled Trial" will be assessed using both primary and secondary endpoints. The primary endpoints include the occurrence of **mean arterial pressure (MAP)** less than 60 mmHg and cardiac arrest. These parameters are critical in evaluating the effectiveness of pre-emptive vasopressor therapy in reducing cardiovascular collapse among critically ill adults undergoing endotracheal intubation.

Secondary endpoints will provide additional insights into the efficacy of the intervention. These include cardiac arrest within 30 minutes from induction, MAP less than 60 mmHg, the lowest systolic blood pressure within 30 minutes from induction, the need for a rescue vasopressor, changes in systolic blood pressure from the last value before induction to the lowest value up to 30 minutes from induction, and severe hypertension defined as MAP greater than 120 mmHg by 30 minutes from induction. The collection and analysis of these endpoints will be conducted at specified time points to ensure comprehensive assessment of the intervention's impact.