Trial Evaluating the Efficacy of Remimazolam in Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (REST)

A Prospective, Open-label, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Remimazolam in patienTs Undergoing Endobronchial Ultrasound-guided Transbronchial Needle Aspiration: REST Trial

Study to evaluate the efficacy and safety of remimazolam in patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration

Primary Outcome Evaluate and compare the success of the procedure in patients undergoing EBUS-TBNA (Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration) when administered with remimazolam in the experimental group, versus Real world midazolam (Control Group 1), and On label midazolam (Control Group 2).

Secondary Outcome In patients undergoing EBUS-TBNA, compare the following aspects when administered with remimazolam in the experimental group versus Real world midazolam (Control Group 1) and On label midazolam (Control Group 2): Procedure start time, Time taken to achieve full alertness, Need for flumazenil administration, Total dose of fentanyl used, Scale of coughing/discomfort/convenience, Changes in vital signs, Complications related to the procedure.

Study Overview

• Status: Not yet recruiting
• Conditions: Remimazolam; Midazolam
• Intervention / Treatment: Drug: Midazolam; Drug: Byfavo

• Study Type: Interventional
• Enrollment (Estimated): 330
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: June Hong Ahn; Phone Number: 821028562008; Email: fireajh@gmail.com

Study Locations

• Korea, Republic of
  • Namgu
    • Daegu, Namgu, Korea, Republic of, 42415
      • Yeungnam University Hospital
      • Contact: June Hong Ahn, M.D. PhD; Phone Number: 821028562008; Email: fireajh@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adult males and females aged 18 and above
2. ASA 1-3
3. BMI 18.5~30.0
4. Saturation pulse oximeter (SpO2) ≥ 90% in ambient air or with no more than 2 liters/min of O2 support
5. Patients who can comply with the procedures according to this clinical study protocol and who have voluntarily signed the consent form themselves

Exclusion Criteria:

1. Patients undergoing radial EBUS or electromagnetic navigation bronchoscopy (ENB) simultaneously
2. ASA 4 or higher
3. Mallampati score 4
4. BMI < 18.5, BMI >30.0
5. Known sensitivity to benzodiazepines, flumazenil, opioids, naloxone, or a medical condition in which these agents
6. Bronchoscopy outside the bronchoscopy unit
7. chronic kidney disease on dialysis
8. Patients with a current active acute infection or uncontrolled chronic inflammatory lung disease
9. Patients considered inappropriate for the study at the investigator's discretion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remimazolam; American Society of Anesthesiologists (ASA) I-II: initial dosing 5mg, maintenance dosing: 2.5mg, interval ≥2minutes ASA III: initial dosing 2.5mg, maintenance dosing: 1.25mg, interval ≥2minutes Remimazolam dose limitation: none Fentanyl: 25-50mcg, interval ≥5mintues, max: 200mcg	Drug: Byfavo; For induction and maintenance of sedation; Other Names: Remimazolam
Active Comparator: Real world Midazolam; Initial dosing 2-3mg, maintenance dosing: 0.5-1mg, interval ≥2minutes Remimazolam dose limitation: 7.5mg Fentanyl: 25-50mcg, interval ≥5mintues, max: 200mcg	Drug: Midazolam; For induction and maintenance of sedation
Active Comparator: On label Midazolam; <60years old and healthy: initial dosing 1.75mg, maintenance dosing: 1.0mg, interval ≥2minutes ≥60years old or debilitated/chronically ill: initial dosing 1.0mg, maintenance dosing: 0.5mg, interval v2minutes Remimazolam dose limitation: 7.5mg Fentanyl: 25-50mcg, interval ≥5mintues, max: 200mcg	Drug: Midazolam; For induction and maintenance of sedation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural success during EBUS-TBNA (composite outcome)	Success of the bronchoscopy procedure, Completion of the bronchoscopy procedure, No requirement for a rescue sedative medication, In the case of remimazolam and placebo, no requirement for more than 5 top-ups of study medication within any 15 minute period; in the case of midazolam, no requirement for more than 3 doses in any 12 minute window	Up to the end of the procedure (up to 1 hour)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to start of procedure after administration of the first dose of study medication	Modified Observer's Assessment of Alertness and Sedation (MOAA/S)≤3 MOAA/S scores: 5 = Responds readily to name spoken in normal tone [alert], 4 =Lethargic response to name spoken in normal tone, 3 = Responds only after name is called loudly and/or repeatedly, 2 = Responds only after mild prodding or shaking, 1 = Responds only after painful trapezius squeeze, 0 = Does not respond to painful trapezius squeeze. MOAA/S scores were assessed by the investigators.	Time from administration of the first dose of study medication to the start of procedure (MOAA/S ≤3) (up to 1 hour)
Time taken to achieve full alertness after the procedure	MOAA/S=5 MOAA/S scores: 5 = Responds readily to name spoken in normal tone [alert], 4 =Lethargic response to name spoken in normal tone, 3 = Responds only after name is called loudly and/or repeatedly, 2 = Responds only after mild prodding or shaking, 1 = Responds only after painful trapezius squeeze, 0 = Does not respond to painful trapezius squeeze. MOAA/S scores were assessed by the investigators.	Time from end of the procedure to first of three consecutive MOAA/S scores =5 (up to 1 hour)
Requirement for flumazenil dosage during the procedure	If MOAA/S score 5 is not reached after bronchoscopy, flumazenil will be administered. Total amount of flumazenil dosage during the procedure is measured. MOAA/S scores: 5 = Responds readily to name spoken in normal tone [alert], 4 =Lethargic response to name spoken in normal tone, 3 = Responds only after name is called loudly and/or repeatedly, 2 = Responds only after mild prodding or shaking, 1 = Responds only after painful trapezius squeeze, 0 = Does not respond to painful trapezius squeeze. MOAA/S scores were assessed by the investigators.	From the end of procedure to discharge of bronchoscopy room (up to 1 hour)
Total fentanyl dose	Total amount of fentanyl during the procedure	From the start of procedure to the end of procedure (up to 1 hour)
Scale of coughing/discomfort/inconvenience	Coughing/discomfort/convenience visual analogue scale (Patients mark a point on a straight line corresponding to their perception of the severity of the cough, discomfort, and inconvenience. VAS ranges 0-100, with 0 representing minimal severity and 100 representing maximal severity)	After the end of procedure (up to 1 hour)
Changes in blood pressure	Changes of blood pressure (mmHg) assessed by 5 minutes	From the start of procedure to the end of procedure (up to 1 hour)
Changes of heart rate	Changes of heart rate (rates/minutes) assessed by 5 minutes	From the start of procedure to the end of procedure (up to 1 hour)
Changes in respiration rate	Changes of respiration rate (rates/minutes) assessed by 5 minutes	From the start of procedure to the end of procedure (up to 1 hour)
Complications related to the procedure	Procedure related complications during 1 month follow up	Up to 1 month

Collaborators and Investigators

• Sponsor: Yeungnam University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Estimated): February 23, 2024

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Efficacy; EBUS-TBNA; Midazolam; Remimazolam
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: YUMC2023-12-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No