Comparative Efficacy of Remimazolam and Midazolam with Fentanyl for Sedation in Screening Colonoscopy: A Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of **Remimazolam** combined with **Fentanyl** compared to **Midazolam** combined with Fentanyl for sedation in screening colonoscopy. The primary outcome measure is the total time from the start of medication to the fulfillment of discharge criteria. This investigation aims to determine whether Remimazolam with Fentanyl can enhance procedural sedation by reducing both the procedure duration and recovery time, which is clinically relevant for improving patient throughput and comfort during colonoscopy screenings.

The clinical trial involves a study population comprising both **male** and **female** participants aged over 18 years, who are scheduled for elective colonoscopy screening for colon cancer. The trial does not include a vulnerable population. Participants must be able to provide informed written consent. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on their eligibility for colonoscopy screening, and no specific lifestyle considerations such as diet or physical activity are mentioned. The study aims to evaluate the efficacy of Remimazolam with Fentanyl compared to Midazolam with Fentanyl for sedation during screening colonoscopy, focusing on the total time from the start of medication to the fulfillment of discharge criteria.

The clinical trial is designed to evaluate the **efficacy** of **remimazolam** with **fentanyl** compared to **midazolam** with **fentanyl** for sedation in screening colonoscopy. This study is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to commence on March 1, 2023, and conclude by September 30, 2023, with the primary objective of assessing the total time from the start of medication to the fulfillment of discharge criteria. The trial will also evaluate secondary endpoints such as the need for postprocedural recovery, patient discomfort, time to reach the cecum, and satisfaction levels of both patients and endoscopists.

Participants will be involved in the study for a maximum treatment period of one day, with the inclusion visit serving as the initial screening to confirm eligibility based on criteria such as age over 18, scheduled elective colonoscopy screening for colon cancer, and the ability to provide informed consent. Follow-up visits will be conducted to monitor the sedation process and assess the primary and secondary endpoints. The end-of-study visit will occur upon the fulfillment of discharge criteria, marking the completion of the participant's involvement.

Participants may be terminated early from the study if they experience adverse reactions that compromise their safety or if they withdraw consent. The investigational medicinal products, including **midazolam hydrochloride**, **remimazolam**, and **fentanyl citrate**, will be administered intravenously, adhering to the authorized usage guidelines. The trial is categorized as low intervention, as the investigational products are authorized and used according to their marketing authorizations, posing minimal additional risk to participants compared to standard clinical practice.

The clinical trial involves the administration of **Midazolam hydrochloride** as part of the experimental treatment. The product used is "Midazolam hameln 5 mg/ml solution for injection/infusion," manufactured by Hameln Pharma GmbH. This pharmaceutical form is a solution intended for intravenous administration. The maximum daily dose is 7.5 mg, with the same amount being the maximum total dose allowed during the treatment period, which is limited to one day. The active substance, midazolam hydrochloride, is of chemical origin and is classified under the ATC code N05CD08. The administration of this medication is monitored to ensure compliance with the dosing schedule.

Another experimental medication used in the trial is **Remimazolam**, provided as "Byfavo 20 mg powder for solution for injection" by Paion Deutschland GmbH. This medication is also administered intravenously after reconstitution into a solution. The maximum daily and total dose is 25 mg, with a treatment period restricted to one day. Remimazolam is a chemically derived substance, and its use in the trial is to evaluate its efficacy in combination with fentanyl for sedation during screening colonoscopy. Compliance with the dosing regimen is closely monitored.

**Fentanyl citrate** is used as an auxiliary treatment in the trial, supplied as "Fentanyl 'Hameln'" by Hameln Pharma GmbH. This medication is available as a solution for injection and is administered intravenously. The dosing is calculated based on body weight, with a maximum daily and total dose of 4 µg/kg. Fentanyl citrate is a chemical substance classified under the ATC code N01AH01. Its role in the trial is to provide sedation in combination with either midazolam or remimazolam, and participant compliance with the dosing schedule is ensured through monitoring.

The efficacy of the investigational medicinal products in this clinical trial will be assessed by comparing **Remimazolam** with **Fentanyl** to **Midazolam** with **Fentanyl** for sedation in screening colonoscopy. The primary endpoint for evaluating efficacy is the total time from the start of medication to the fulfillment of discharge criteria. This will determine if Remimazolam with Fentanyl can lead to a shorter procedure and recovery time compared to Midazolam with Fentanyl.

Secondary endpoints include several parameters: the need for a postprocedural recovery room due to lack of fulfillment of discharge criteria, patient discomfort or pain rated using the NRS-11 scale, time to reach the coecum, the need for additional Fentanyl or sedatives, patient satisfaction, endoscopist satisfaction, and cognitive function at discharge. These endpoints will provide a comprehensive assessment of the sedation efficacy and overall procedural experience.