Efficacy and Safety of Propofol/Pethidine Versus Midazolam/Pethidine for Analgosedation in Bronchoscopic Procedures: A Randomized Controlled Trial

The primary objective of this study is to assess and compare the **safety** and **efficacy** of two pharmacological regimens, Propofol + Pethidine versus Midazolam + Pethidine, administered independently by the medical staff of Pulmonology and RICU at San Donato Hospital in Arezzo. This evaluation is crucial for facilitating procedural sedation in patients undergoing bronchoscopic procedures, which are essential for the diagnosis and management of various respiratory diseases. The clinical relevance of this objective lies in optimizing sedation protocols to enhance patient safety and procedural outcomes.

Secondary objectives include evaluating and comparing peri- and post-procedural complications, such as cardiovascular and respiratory adverse events, as well as drug reactions. Additional metrics include procedural tolerance, procedure duration, average drug dosage, and final diagnostic outcomes of the procedures performed.

The clinical trial involves **patients** undergoing bronchoscopic procedures with **analgosedation** for the diagnosis and management of various respiratory diseases. The study population includes adults over the age of 18, comprising both male and female participants. These individuals are required to be capable of understanding and providing informed consent and are scheduled for elective bronchoscopy, with or without echoendoscopy, for diagnostic, staging, or therapeutic purposes. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' general health status, lifestyle considerations such as diet, physical activity, or habits, are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy** and safety of two pharmacological regimens, **Propofol** combined with **Pethidine** versus **Midazolam** combined with **Pethidine**, in facilitating procedural sedation during bronchoscopic procedures. This study is a single-centre, randomized, controlled trial, classified as a low-intervention clinical trial, as the investigational medicinal products are used in accordance with their marketing authorization, posing minimal risks compared to normal clinical practice. The trial is expected to commence on February 15, 2025, and conclude by February 15, 2027, with the primary endpoint being the comparison of the desaturation index (SpO2 < 90% for at least 30 seconds) between the two drug regimens. Secondary endpoints include the assessment of adverse events, procedural tolerance, serious adverse events, procedure time, and final diagnostic yield.

Participants will be involved in the study for a maximum treatment period of one day, with the inclusion visit serving as the screening phase to ensure eligibility criteria are met. Eligible participants are adults over 18 years, capable of providing informed consent, and scheduled for elective bronchoscopy. The study will exclude individuals who do not meet these criteria. The trial will involve a series of study visits, beginning with the inclusion visit, followed by the administration of the assigned drug regimen during the bronchoscopic procedure. Follow-up visits will be conducted to monitor safety and efficacy outcomes, with the end-of-study visit marking the conclusion of participant involvement. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or withdrawal of consent by the participant.

The clinical trial involves the administration of **Propofol**, a chemical substance with the active ingredient name **Propofol**. It is administered in the form of an infusion with a pharmaceutical form code PHF742. The dosage is measured in milligrams per kilogram per hour (mg/kg/h), with a maximum daily dose of 1.0 mg/kg/h and a total maximum dose of 4.0 mg/kg/h. The treatment period is limited to one day. Propofol is utilized as an anesthetic in this study.

**Midazolam** is another experimental medication used in this trial. It is administered via infusion, with a pharmaceutical form code PHF00230MIG. The active substance is **Dobutamine Hydrochloride**, although the product is referred to as Midazolam. The dosage is expressed in milligrams (mg), with a maximum daily dose of 2 mg and a total maximum dose of 5 mg. The treatment period is also restricted to one day.

**Pethidine Hydrochloride** is the third experimental medication, administered through infusion with a pharmaceutical form code PHF00231MIG. The dosage is calculated in milligrams per kilogram (mg/kg), with a maximum daily dose of 0.5 mg/kg and a total maximum dose of 600 mg. The treatment duration is limited to one day. Pethidine Hydrochloride is also known by the synonym Meperidine Hydrochloride.

In this study, the experimental treatments are compared against each other in two regimens: Propofol combined with Pethidine versus Midazolam combined with Pethidine. The trial aims to evaluate the safety and efficacy of these pharmacological regimens in facilitating procedural sedation during bronchoscopic procedures. Participant compliance and dosing schedules are monitored to ensure adherence to the study protocol.

The efficacy of the clinical trial titled "Efficacy and safety of Balanced Analgosedation in Bronchoscopy with Propofol/Pethidine versus Midazolam/Pethidine: a single-centre randomised controlled trial (ABroProMida Study)" will be assessed by evaluating and comparing the **desaturation index** (SpO2 < 90% for at least 30 seconds) between the two drug regimens: Propofol + Pethidine and Midazolam + Pethidine. This primary endpoint will provide a direct measure of the efficacy of the sedation regimens in maintaining adequate oxygenation during bronchoscopic procedures.

Secondary endpoints include the assessment of adverse events (AEs), procedural tolerance using scores such as the Aldrete score, serious adverse events (SAE), procedure time, and final diagnostic yield. These parameters will be collected and analyzed to provide a comprehensive evaluation of the safety and efficacy of the sedation regimens. The trial is designed as a low-intervention clinical trial, ensuring that the investigational medicinal products are used in accordance with their marketing authorization, with minimal additional risks or burdens compared to normal clinical practice.