A Randomized Single-blind Clinical Trial of the Efficacy and Safety of Remimazolam in Painless Bronchoscopy

Over the past decade, bronchoscopy technology has developed rapidly and has become an important part of the diagnosis and treatment of respiratory diseases. Bronchoscopy are usually carried out under monitored anesthesia care (MAC), which can relieve the anxiety of the patient, make the operation easier, and improve the completion rate of bronchoscopy. At present, bronchoscopy has widely used midazolam, propofol, short-acting opioids, and newer sedatives such as dexmedetomidine, but each drug has its limitations. Dexmedetomidine is widely used in non-intubation general anesthesia and sedation during short outpatient surgery. However, rapid and high-dose infusion of dexmedetomidine leads to dose-dependent hypotension, temporary hypertension, bradycardia, and excessive sedation, causing hemodynamic fluctuations. At the same time, it has slow onset and metabolism. This may be a potential risk for some elderly patients with many underlying diseases and unstable hemodynamics. Remimazolam is an ultra-short-acting benzodiazepine. It has the advantages of short action time, low accumulation, low risk of respiratory depression, and reversibility. We believe that remimazolam can improve the onset time and resuscitation time, to achieve sufficient sedation, improve the success rate of bronchoscopy, while reducing the patient's oxygen saturation drop during the operation, postoperative opioid-related nausea and vomiting, postoperative delirium and other related adverse events. This study is a randomized controlled trial to confirm the above hypothesis.

Study Overview

• Status: Recruiting
• Conditions: Sedation; Bronchoscopy
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Remimazolam

Detailed Description

All patients undergoing bronchoscopy under general anesthesia will be recruited and should complete relevant preoperative examinations. The patient fasted for 6-8 hours before the operation, and an indwelling trocar was placed in the vein. After entering the room, the patient will be monitored with electrocardiogram(ECG), pulse oximetry, non-invasive blood pressure, and underwent oxygen inhalation (5L/min) through a nasal cannula. All patients used 2% lidocaine glue to moisten the nasal cavity for local anesthesia before the operation, the bronchoscope was inserted through the nose. The subjects take a supine position. When the bronchoscope passes through the vocal cords and carina, 5 ml of 2% lidocaine is delivered through the channel to suppress the cough reflex. Then the patients were randomly divided into two groups:

1. one group use dexmedetomidine-remifentanil for anesthesia: the initial dose of dexmedetomidine is 0.1ml/kg, infused for 5 minutes, and then adjusted to 0.1-0.5ml/kg/h; the initial dose of remifentanil is 0.05ml/kg, infused for 5 minutes, and then adjusted to 0.1- 0.5 ml/kg/h.
2. the other group use remimazolam-remifentanil for anesthesia: the initial dose of remimazolam is 0.1ml/kg, infused for 5 minutes, and then adjusted to 0.1-0.5ml/kg/h; the initial dose of remifentanil is 0.05ml/kg, infused for 5 minutes, and then adjusted to 0.1- 0.5 ml/kg/h.

All patients started bronchoscopy when they reached TE sedation (modified observer's assessment of sedation,MOAA/S score 3 points). If the assessment of sedation after administration suggests that the sedation is insufficient, propofol 0.4-0.6 mg/kg is repeatedly administered every 5 minutes, with the maximum dose not exceeding 200 mg to maintain sedation. In the maintenance phase of sedation, appropriate sedation is pre-defined as a MOAA/S score of 4 or less. The drug was continuously infused until the end of the bronchoscopy, and all patients were transferred to the post-anaesthesia care unit (PACU) for further observation.

Data from the DoCare Clinic electronic anesthesia recording system was used in this experiment. Bronchoscopy was performed by the same bronchologist with more than 10 years of experience.

• Study Type: Interventional
• Enrollment (Anticipated): 364
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University Medical College
      • Contact: Min Yan, MD; Phone Number: 15888210247; Email: zryanmin@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 to 70 years old.
2. Need for bronchoscopy (for example, unexplained cough, hemoptysis, localized wheezing and hoarseness, chest X-ray and/or CT scans suggest abnormalities, examination and evaluation of lungs before surgery, chest trauma, lungs Or bronchial infectious disease).
3. ASA classification I-III level.
4. BMI≤30kg/m2.
5. Women of childbearing age have a negative pregnancy test.
6. Before the study, the patients voluntarily signed and dated the informed consent form approved by the institutional review board.

Exclusion Criteria:

1. Patients with known allergies to benzodiazepines, flumazenil, opioids, naloxone or certain drugs.
2. Patients with long-term use of benzodiazepines or opioids.
3. Patients with a history of drug abuse or alcohol abuse in the past two years.
4. Bradycardia (baseline HR <60bpm) or hypotension (baseline SAP<100mmHg).
5. Asthma or chronic obstructive pulmonary disease(COPD) or FEV1<1.0L.
6. SpO2 <90% before bronchoscopy.
7. Patients who received any study drug within 30 days before screening or less than 7 half-lives of the drug.
8. Any patient with cognitive impairment or inability to provide informed consent.

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: Control group; Patients receive dexmedetomidine for sedation	Drug: Dexmedetomidine; Sedation with dexmedetomidine; Other Names: Remifentanil
Experimental: Test group; Patients receive remimazolam for sedation	Drug: Remimazolam; Sedation with remimazolam; Other Names: Remifentanil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Decreased Oxygen Saturation [ Safety]	Oxygen Saturation<90%, more than 30s	Within 1 hour after the operation
Interruption Rate of Bronchoscopy [effectiveness]	the occurrence of body movement or coughing makes the operating physician have to suspend the operation for physical restraint or adding drugs	Within 1 hour after the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	Hemodynamic variable	Within 1 hour after the operation
Heart Rate	Hemodynamic variable	Within 1 hour after the operation
Hemodynamic variable	SpO2	Within 1 hour after the operation
Respiratory Rate	Hemodynamic variable	Within 1 hour after the operation
Anesthesia onset time	onset time (min)	Within 1 hour after the operation
Remedial drug demand dose of the two groups of patients	Remedial drug demand dose	Within 1 hour after the operation
Satisfaction Scores of The Operating Physicians	Satisfaction Scores (0-5,higher scores mean a better outcome.)	Within 1 hour after the operation
Incidence of adverse reactions		Within 1 hour after the operation
Incidence of operation-related complications		Within 1 hour after the operation
Anesthesia resuscitation time	resuscitation time (min)	Within 1 hour after the operation

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2021
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: remimazolam, dexmedetomidine, bronchoscopy, sedation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Remifentanil; Dexmedetomidine
• Other Study ID Numbers: 2021-0058

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
• product manufactured in and exported from the U.S.: No