A Comparison of Remimazolam Besylate and Propofol Sedation in Patients Undergoing Colonoscopic Polypectomy (Bypro)

The goal of this prospective, randomized, controlled study is to compare remimazolam besilat/sufentanyl and propofol/sufentanyl in patients during colonoscopic polypectomies procedures.

Patients undergoing colonoscopic polypectomies in procedural sedation using remimazolam besylate/sufentanyl are circulatory and respiratory as or more stable when compared with propofol/sufentanyl sedation.

Study Overview

• Status: Recruiting
• Conditions: Colonic Polyp; Sedation Complication
• Intervention / Treatment: Drug: Remimazolam besylate; Drug: Propofol

Detailed Description

Following the approval for the research by the Ethics Committee (Clinical Hospital Center, Zagreb, Croatia), a total of ninety (90) patients will be included in the research. Forty five (45) patients will be assigned to the study group (SG) and forty five (45) patients to the control group (CG).

Research Goals:

Primary goals

1. Observe and compare circulatory and respiratory stability in patients undergoing procedural sedation with either remimazolam besylate or propofol during colonoscopic polypectomies
2. Define and compare the incidence of hypotension between the study grou and the control group.
3. Define and compare the incidence of respiratory depression between the study group and the control group.

Secondary goals

1. Define and compare the success of remimazolam besylate sedation compared with propofol.
2. Define and compare the time required to achieve adequate sedation between the two observed groups.
3. Define and compare the time to achieve full consciousness between the two observed groups.
4. Define and compare the time to complete recovery between the two groups.

Patients from both groups, upon arrival to the gastroenterology ward will have a peripheral venous line installed by puncturing one of the veins on the dorsum of the hand or forearm. The veins of choice include the rete venosum dorsale manus, vena cephalica and vena basilica, and an 18 G or 20 G intravenous cannula will be placed. After confirming the functionality of the venous line, the intravenous administration of Fifty will follow. The infusion rate will depend on the patient's BMI and circulatory status.

Study Group (SG):

A total of 45 patients are included in this group. After non-invasive monitoring, positioning the patient in the left lateral position and placing a nasal catheter with a continuous oxygen flow of 3 l/min, the patient will receive the intravenous opioid analgesic Sufentanyl 0.2 mcg/kg over a period of 30 seconds.

After 1 to 2 minutes the patient will receive remimazolam besylate intravenously in a dose of 5.0 mg over a period of 1 minute. After two minutes, a maintenance dose of 2.5 mg will be administered using the titration method over a period of 15 seconds until the desired sedation effect is achieved.The maximum intravenous dose of administered remimazolam besylate will be 33 mg.BIS monitoring and a modified MOAA/S (Modified Observers Assessment of Alertness and Sedation Scale) scale will be used to assess the depth of sedation. The first measurement of the depth of sedation will be initially following the complete administration of the sedative remimazolam besylate and will serve as the initial/starting point. Afterwards, a measurement of the MOAA/S scale will be performed every 30 seconds for a total of 3 minutes. The most desirable level of sedation for the planned procedure is defined as a MOAA/S measurement of <3.

Control group (CG)

A total of 45 patients will be included in this group.

Firstly, non-invasive monitoring will be applied to the patient, then they will be placed in the left lateral position and through a nasal catheter a continuous oxygen flow of 3l/min will be administered. The patient will be given intravenous opioid analgesia Sufentanyl 0.2 mg/kg. within 30 seconds. After approximately 1-2 minutes the patient will receive the titrated anesthetic propofol intravenously at a dose of 1.5 to 2.5 mg/kg, (20.0 to 30.0 mg propofol every 10 seconds). In elderly patients and patients with ASA grade III, the total dose of propofol will be at least 1 mg/kg with an administration rate of 10.0 to 20.0 mg every 10 seconds.

Sedation will be maintained using propofol in a continuous intravenous infusion. The maintenance dose given will be 0.5 to 1.0 mg propofol/kg/hour.

BIS monitoring and a modified MOAA/S (Modified Observers Assessment of Alertness and Sedation Scale) scale will be used to assess the depth of sedation. The first measurement of the MOAA/S score will be conducted after the total intravenous propofol dose was administered and this first measurement will be considered the starting/zero measurement. MOAA/S scale point will be measured every 30 seconds for a total of 3 minutes. A measurement of <3 points will be considered the most desirable level of sedation for the planned procedure.

In both study groups the following parameters will continuously be measured:

1. Pulse oxymetry (SpO2), respiratory rate (RR), EKG, heart rate (HR) and rhythm, systolic, diastolic and mean arterial pressure.
2. Circulatory parameters including systolic, diastolic and mean arterial pressure will be measured:

Primary measurement:

Upon patients' arrival to the pre-op room (first measurement) and 5 minutes before proceeding to the operating theater.

During the procedure:

Before administering the sedative remimazolam besylate or propofol and at 3, 5, 10, and 15 minutes. (every 5 minutes during the procedure) until the patient is consciousness, followed by the first of five sets of MOAAS/S measurements upon completion of the procedure or when the last dose of medication is given.

Frequency of hypotension in both groups of patients and comparing the results between the SG and CG.

Hypotension during the procedure using sedation or propofol is defined as:

a decrease in systolic systemic pressure of 20% or more compared with the first measurement before the administration of remimazolam besylata or propofol.

A mean arterial pressure of ≤60 mmHg during while the patient is under sedation.

4. Sinus bradycardia is defined as a decreased cardiac rate. 5. The frequency of respiratory depression compared between the two groups, SG and CG.

Respiratory depression during sedation is defined as:

Respiratory rate of <8 breaths per minute and/or a peripheral blood oxygen percentage of (SpO2) <90.

6. BIS monitoring. 7. The success of procedural sedation using remimazolam besylate and sedation using propofol:

Will be shown as the percentage of successfully sedated patients defined as:

The completion of endoscopic polypectomy, without the need for rapid/fast acting emergency sedation or a maximum number of 5 additional doses given withing 15 minutes of the first dose to maintain adequate sedation.

8. The time to achieve adequate sedation is defined as the time from administering the first dose of medication until achieving <3 points on the MOAA/S scale and/ora BIS.

9. The time to achieve full consciousness is defined as the time since the administration of the last dose of medication until the patient is fully aware, or until the patients has 5 points on the MOAA/S scale.

10. The time needed for the patient to fully recover after the procedure in both groups is defined by the criteria for patient dismissal using the - Modified Aldrete score scale.

The total volume of the given crystalloid solution (Plasma-lyte) will be measured in both groups.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Željko Drvar, MD, PhD; Phone Number: 003851 2388 888; Email: zeljko.drvar@kbc-zagreb.hr

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • Recruiting
    • UHC Zagreb
    • Contact: Željko Drvar, MD, PhD; Phone Number: 003851 2388 888; Email: zeljko.drvar@kbc-zagreb.hr
    • Principal Investigator: Željko Drvar, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients both male and female
• ages 18 to 60 years,
• with one or more colonic polyps confirmed by colonoscopy and scheduled for a colonoscopy and polypectomy
• The duration of the colonoscopy ranges from 30 to 50 minutes.
• ASA status (American Society of Anaesthesiologists physical status) I-III.
• BMI (Body mass index) 18.5-29.9 kg/m2.
• Only patients who signed an informed consent waiver and consented to participate in the research study.

Exclusion Criteria:

• Patients aged >60 years
• ASA status IV-V,
• BMI >29.9 kg/m2,
• a high risk of vomiting, regurgitation and/or aspiration of gastric contents.
• Patients with:
• uncontrolled hypertension (systolic pressure >160 mmHg),
• heart disease (cardiomyopathy, cardiac-rhythm disorder, left ventricular ejection fraction <45%, stenosis or heart valve insufficiency and coronary heart disease)
• lung disease (pneumonia, chronic obstructive pulmonary disease, asthma and pulmonary tumors),
• kidney diseases (kidney failure, GF 30/59 ml/min/1.73m2),
• liver diseases,
• coagulation disorders
• lymphatic tissue diseases
• extended malignant disease.
• History of allergy on nutritional allergens including soy bean, benzodiazepines, propofol or opioids.
• Patients who currently use analgesic medications or other psycho-pharmaceuticals.
• History of illicit drug use.
• Children, pregnant and nursing women.
• Alcohol dependency.
• Patients involved in other clinical research studies,
• patients who refused to take part in the research or have not signed the written informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propofol	Drug: Propofol; The patient will be given intravenous opiod analgesia sufentanyl 0,2 mg/kg.within 30 seconds. After approximately 1-2 minutes the patient will receive the titrated anestetic propofol intravenously at a dose of 1,5 to 2,5 mg/kg (20,0 mg. propofol evry 10 seconds). In elderly patients and patients with ASA grade III, the total dose of propofol will be least 1 mg/kg with an administration rate of 10 every 10 seconds.
Experimental: Remimazolam besylat	Drug: Remimazolam besylate; The patient will receive the intravenous opioid analgesic sufentanyl 0.2 mcg/kg over a period of 30 seconds. After 1 to 2 minutes the patient will receive remimazolam besylate intravenously in a dose of 5.0 mg over a period of 1 minute. After two minutes, a maintenance dose of 2.5 mg will be administered using the titration method over a period of 15 seconds until the desired sedation effect is achieved.The maximum intravenous dose of administered remimazolam besylate will be 33 mg.BIS monitoring and a modified MOAA/S scale will be used to assess the depth of sedation. The first measurement of the depth of sedation will be initially following the complete administration of the sedative remimazolam besylate and will serve as the initial/starting point. Afterwards, a measurement of the MOAA/S scale will be performed every 30 seconds for a total of 3 minutes. The most desirable level of sedation for the planned procedure is defined as a MOAA/S measurement of <3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic Stability - Mean Arterial Pressure (MAP)	Mean arterial pressure (mmHg) measured at multiple timepoints to assess overall circulatory stability. Comparison of MAP values between remimazolam and propofol groups.	from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant.
Hemodynamic Stability - Systolic and Diastolic Blood Pressure	Systolic and diastolic blood pressure (mmHg) measured at multiple timepoints to assess circulatory stability. Comparison between remimazolam and propofol groups.	from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant.
Hemodynamic Stability - Heart Rate	Heart rate (beats per minute) measured continuously via ECG monitoring. Comparison of heart rate values between study groups.	from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant.
Incidence of Hypotension	Percentage of participants experiencing hypotension defined as either: Decrease in systolic blood pressure ≥20% from baseline value (measured before remimazolam or propofol administration), OR Mean arterial pressure (MAP) ≤60 mmHg during procedural sedation	from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant.
Incidence of Bradycardia	Bradycardia is defined as a heart rate (HR) below 50 beats per minute (bpm), or a clinically significant decrease in HR of ≥20% from the pre-induction baseline, sustained for ≥1 minute and/or requiring pharmacological or non-pharmacological intervention (e.g., atropine administration, reduction or discontinuation of the study drug). HR will be continuously monitored via standard intraoperative ECG monitoring and recorded at predefined time points: baseline (pre-induction), immediately post-induction (T1), at 5-minute intervals intraoperatively, at emergence from anesthesia, and at 15 and 30 minutes postoperatively in the post-anesthesia care unit (PACU). The incidence of bradycardia will be expressed as the proportion of patients experiencing at least one episode meeting the above criteria within the defined observation window.	from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant.
Respiratory Stability - Oxygen Saturation (SpO₂)	Peripheral oxygen saturation (%) measured continuously via pulse oximetry. Comparison of SpO₂ values between study groups.	from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant.
Incidence of Respiratory Depression	Percentage of participants experiencing respiratory depression defined as: Respiratory rate <8 breaths per minute, AND/OR Peripheral oxygen saturation (SpO₂) <90%	from enrollment up to 2 hours after the procedure; approximately 2-4 hours per participant.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural Sedation Success Rate	Percentage of participants achieving successful sedation defined as: Completion of entire endoscopic polypectomy procedure, AND No need for rescue sedation (defined as propofol 1.5-2.5 mg/kg IV by titration for inadequate sedation level in either group), AND Maximum of 5 additional drug doses within 15 minutes of initial dose	During the endoscopic procedure (estimated 30-50 minutes
Time to Adequate Sedation Level	Time in minutes from first drug dose to achievement of adequate sedation level, defined as MOAA/S (Modified Observer's Assessment of Alertness/Sedation) score <3 AND/OR BIS (Bispectral Index) value 50-70	From first drug administration until adequate sedation achieved (estimated 1-5 minutes)
Time to Full Alertness	Time in minutes from last drug dose to full patient alertness, defined as achieving MOAA/S score of 5	From last drug administration until full alertness (estimated 10-20 minutes post-procedure)
Time to Recovery Room Discharge Readiness	Time in minutes from last drug dose to patient meeting discharge criteria from recovery room using Modified Aldrete Scoring System	From last drug administration until meeting discharge criteria (estimated 15-30 minutes post-procedure)
Depth of Sedation - BIS Values	Bispectral Index (BIS) values (0-100 scale) measured continuously to assess depth of sedation. Target range 50-70. Comparison of BIS values between study groups throughout procedure.	From baseline through procedure completion until full alertness (estimated 30-60 minutes)
Depth of Sedation - MOAA/S Scores	Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores (0-5 scale) measured at baseline, after total drug dose (time zero), then every 30 seconds for 3 minutes. Target score <3 for adequate sedation.	Baseline, immediately after drug administration, then every 30 seconds for 3 minutes, then as clinically indicated during procedure
Total Drug Dosage	Total dose of remimazolam besilate (mg) administered during procedure in the intervention group and total dose of propofol (mg) administered during procedure in the control group. Total dose of sufentanil (micrograms) administered in both groups (0.2 mcg/kg initial dose)	During procedure (estimated 30-50 minutes)
Procedure and sedation duration	Duration of sedation and colonoscopic polypectomy procedure in minutes	From first drug administration to full alertness (estimated 30-60 minutes) From procedure start to procedure completion (estimated 30-50 minutes)
Total Crystalloid Infusion Volume	Total volume (mL) of Plasma-Lyte crystalloid solution administered during procedure	During procedure and recovery (estimated 30-90 minutes)
Incidence of Post-Procedure Pain, nausea and vomiting	Percentage of participants experiencing pain, nausea or vomiting in the post-procedure period	ost-procedure assessment before recovery room discharge (estimated 30-60 minutes after last drug dose)
Satisfaction Score	Patient-reported satisfaction with sedation procedure (VAS from 0-10) Endoscopist-reported satisfaction with sedation quality for procedure performance (VAS from 0-10)	Post-procedure before recovery room discharge

Collaborators and Investigators

• Sponsor: Clinical Hospital Centre Zagreb

Publications and helpful links

General Publications

• Borkett KM, Riff DS, Schwartz HI, Winkle PJ, Pambianco DJ, Lees JP, Wilhelm-Ogunbiyi K. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg. 2015 Apr;120(4):771-80. doi: 10.1213/ANE.0000000000000548.
• Sahinovic MM, Struys MMRF, Absalom AR. Clinical Pharmacokinetics and Pharmacodynamics of Propofol. Clin Pharmacokinet. 2018 Dec;57(12):1539-1558. doi: 10.1007/s40262-018-0672-3.
• Hinkelbein J, Lamperti M, Akeson J, Santos J, Costa J, De Robertis E, Longrois D, Novak-Jankovic V, Petrini F, Struys MMRF, Veyckemans F, Fuchs-Buder T, Fitzgerald R. European Society of Anaesthesiology and European Board of Anaesthesiology guidelines for procedural sedation and analgesia in adults. Eur J Anaesthesiol. 2018 Jan;35(1):6-24. doi: 10.1097/EJA.0000000000000683.
• Rex DK, Bhandari R, Desta T, DeMicco MP, Schaeffer C, Etzkorn K, Barish CF, Pruitt R, Cash BD, Quirk D, Tiongco F, Sullivan S, Bernstein D. A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2018 Sep;88(3):427-437.e6. doi: 10.1016/j.gie.2018.04.2351. Epub 2018 Apr 30.
• Zhu X, Wang H, Yuan S, Li Y, Jia Y, Zhang Z, Yan F, Wang Z. Efficacy and Safety of Remimazolam in Endoscopic Sedation-A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021 Jul 26;8:655042. doi: 10.3389/fmed.2021.655042. eCollection 2021.
• Qiu Y, Gu W, Zhao M, Zhang Y, Wu J. The hemodynamic stability of remimazolam compared with propofol in patients undergoing endoscopic submucosal dissection: A randomized trial. Front Med (Lausanne). 2022 Aug 8;9:938940. doi: 10.3389/fmed.2022.938940. eCollection 2022.
• Guo J, Qian Y, Zhang X, Han S, Shi Q, Xu J. Remimazolam tosilate compared with propofol for gastrointestinal endoscopy in elderly patients: a prospective, randomized and controlled study. BMC Anesthesiol. 2022 Jun 10;22(1):180. doi: 10.1186/s12871-022-01713-6.
• Xin Y, Chu T, Wang J, Xu A. Sedative effect of remimazolam combined with alfentanil in colonoscopic polypectomy: a prospective, randomized, controlled clinical trial. BMC Anesthesiol. 2022 Aug 16;22(1):262. doi: 10.1186/s12871-022-01805-3.
• Chen SH, Yuan TM, Zhang J, Bai H, Tian M, Pan CX, Bao HG, Jin XJ, Ji FH, Zhong TD, Wang Q, Lv JR, Wang S, Li YJ, Yu YH, Luo AL, Li XK, Min S, Li L, Zou XH, Huang YG. Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial. J Gastroenterol Hepatol. 2021 Feb;36(2):474-481. doi: 10.1111/jgh.15188. Epub 2020 Jul 24.
• Dossa F, Megetto O, Yakubu M, Zhang DDQ, Baxter NN. Sedation practices for routine gastrointestinal endoscopy: a systematic review of recommendations. BMC Gastroenterol. 2021 Jan 7;21(1):22. doi: 10.1186/s12876-020-01561-z.
• Kim KM. Remimazolam: pharmacological characteristics and clinical applications in anesthesiology. Anesth Pain Med (Seoul). 2022 Jan;17(1):1-11. doi: 10.17085/apm.21115. Epub 2022 Jan 20.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: January 12, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Polypectomy; Propofol; Procedural sedation; Respiratory depression; Remimazolam besylate; Circulatory stability; Respiratory stability
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Respiratory Tract Diseases; Respiration Disorders; Polyps; Intestinal Polyps; Pathological Conditions, Signs and Symptoms; Respiratory Insufficiency; Colonic Polyps; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Propofol
• Other Study ID Numbers: LOC-100018379

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Individual participant data will not be shared due to regulatory, ethical, and practical constraints. Croatian healthcare data protection law (NN 14/19) and GDPR regulations mandate strict safeguarding of personal health information. The informed consent obtained from participants explicitly limits data use to this specific study and does not authorize sharing of individual-level data with external parties. Given the relatively small sample size (n=100) and the specific clinical context at a single tertiary center, there is meaningful risk of participant re-identification even with standard de-identification procedures.

Additionally, our institution lacks the technical infrastructure for secure data repository management and controlled access mechanisms necessary for responsible IPD sharing. Resources for comprehensive data curation, security auditing, and long-term stewardship were not included in the study budget.

However, we are committed to research transparency.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No