A Randomized Controlled Trial Comparing Remimazolam and Midazolam for Sedation in Diagnostic Upper Gastrointestinal Endoscopy

The primary objective of this study is to evaluate the **duration** required for complete patient recovery following the administration of **midazolam** and **remimazolam** for procedural sedation during diagnostic upper gastrointestinal (GI) endoscopies. This is clinically relevant as it may influence the choice of sedative agents, impacting patient throughput and resource utilization in endoscopy units.

Secondary objectives include:

• Evaluating the duration between arrival in the recovery room and complete patient recovery.
• Assessing the duration required for patients to reach readiness for discharge.
• Evaluating the satisfaction of patients and endoscopists.
• Assessing the duration of post-procedural amnesia.
• Evaluating procedural sedation success rates.
• Assessing adverse events.

The clinical trial involves a study population comprising both **male** and **female** participants aged 18 years and older. The trial does not include a vulnerable population. Participants are required to be scheduled for a diagnostic upper gastrointestinal endoscopy with procedural sedation. The ability to provide written informed consent and comprehend the responsibilities of trial participation is mandatory. The sponsor has not provided information regarding the total number of participants. The selection criteria focus on adults who are undergoing specific medical procedures, without additional lifestyle considerations such as diet or physical activity being specified. Key inclusion criteria include the age requirement and the necessity for procedural sedation during the endoscopy. The trial aims to evaluate the duration required for complete patient recovery following the administration of midazolam and remimazolam.

The clinical trial is designed as a **randomized controlled trial** to evaluate the duration required for complete patient recovery following the administration of **midazolam** and **remimazolam** for procedural sedation during diagnostic upper gastrointestinal (GI) endoscopies. The trial will involve adult patients aged 18 years and older who are scheduled for a diagnostic upper GI endoscopy with procedural sedation and are capable of providing written informed consent. The study will employ a double-blind methodology to ensure unbiased results, with participants randomly assigned to receive either midazolam or remimazolam. The trial is expected to commence recruitment on September 1, 2024, and conclude by September 1, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the inclusion criteria. During this visit, informed consent will be obtained, and baseline assessments will be conducted. The primary endpoint of the study is the time to full alertness, defined as the interval from the last dosage of the sedative to achieving full alertness, evaluated using the MOAA/S score. Secondary endpoints include the time to readiness for discharge, patient and endoscopist satisfaction, post-sedation amnesia, the success rate of sedation, and the incidence of adverse events related to the sedatives.

Follow-up visits will be scheduled to monitor recovery and assess the secondary endpoints. The end-of-study visit will mark the completion of the participant's involvement, where final assessments will be conducted, and any remaining queries addressed. The expected length of participant involvement is approximately one day, corresponding to the duration of the endoscopy procedure and immediate recovery period. Conditions that may lead to early termination from the study include withdrawal of consent, occurrence of significant adverse events, or any protocol deviations that compromise the integrity of the trial data.

The clinical trial involves the administration of two experimental medications for sedation during upper gastrointestinal (GI) endoscopy. The first medication is **Midazolam**, marketed under the name "Midazolam Viatris 1 mg/ml oplossing voor injectie." This medication is provided in the form of a **solution for injection** and is administered via **intravenous bolus injection or IV infusion**. The maximum daily dose is 20 mg, with a total maximum dose of 100 mg allowed over the course of the treatment period, which is limited to one day. Midazolam is a chemical substance classified under the ATC code N05CD08 and is not a pediatric formulation. The product is manufactured by VIATRIS GX and holds the marketing authorization number BE339376 in Belgium.

The second medication used in the trial is **Remimazolam**, marketed as "Byfavo 20 mg powder for solution for injection." This medication is initially provided as a **powder** that is reconstituted into a solution for injection, also administered via **intravenous bolus injection or IV infusion**. The maximum daily dose for Remimazolam is 25 mg, with a total maximum dose of 100 mg over a one-day treatment period. Remimazolam is a chemical substance with the ATC code N05CD14 and is also not formulated for pediatric use. The product is manufactured by PAION DEUTSCHLAND GMBH and holds the marketing authorization number EU/1/20/1505/001 in Liechtenstein.

Both medications are used in the trial to evaluate the duration required for complete patient recovery following procedural sedation during diagnostic upper GI endoscopies. The trial is designed as a randomized controlled study to compare the efficacy and safety of Remimazolam versus Midazolam. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the specified administration protocols.

Efficacy in this clinical trial will be assessed by evaluating the duration required for complete patient recovery following the administration of **midazolam** and **remimazolam** for procedural sedation during diagnostic upper gastrointestinal (GI) endoscopies. The primary endpoint is the time to full alertness, defined as the time interval from the last dosage of the sedative to full alertness. Full alertness is measured using the validated MOAA/S score, with full alertness defined as the first of three consecutive MOAA/S scores of at least 5.

Secondary endpoints include the time interval between patient arrival in the recovery room and full alertness, and the time to readiness for discharge, which is evaluated using the Aldrete score. Readiness for discharge is defined as the first Aldrete score of at least 9. Patient satisfaction will be assessed using a modified version of the Patient Satisfaction with Sedation Instrument (PSSI), focusing on global satisfaction and procedural recall. Endoscopist satisfaction will be scored directly after the procedure on a scale from 0 to 10. Post-sedation amnesia will be evaluated using a self-developed amnesia test. The success rate of sedation is defined as the percentage of procedures completed as intended without requiring more than five boluses of the sedatives or an alternative sedative. Additionally, the incidence of adverse events related to midazolam and remimazolam will be recorded.