Comparative Clinical Study of Efficacy and Safety of Remimazolam and Propofol in Patients Undergoing Elective Surgery Under General Anaesthesia

NCT03669484 | Completed Phase 3

• 1 other identifier: CN01082020
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study was to perform comparative evaluation of clinical efficacy and safety of Remimazolam and Propofol for induction and maintenance of general anesthesia in patients undergoing elective surgery under general anaesthesia.

Conditions

General Anaesthesia

Keywords

anaesthesia; surgery

Outcome Measures

Primary Outcomes (1)

• ANAESTassessment

  "Action as a general anesthetic", a compound evaluation criterion, consisted of the following criteria. The test drug/comparator were considered effective in patients who had not had any of the following criteria and ineffective in patients who had at least one of the following criteria: 1. Intraoperative awakening/preservation of memories of surgery; 2. The need for additional sedatives.

  During the surgery and 24 hours after the study drugs administration

Secondary Outcomes (7)

• TIMEextub

  From the moment of discontinuation of the test drug / comparator to restoration of spontaneous breathing and removal of the endotracheal tube on Day 1 of treatment

• TIMEopeneyes

  From the moment of discontinuation of the test drug / comparator to eye opening on Day 1 of treatment

• TIMEunconsc

  From the onset of administration of the test drug/comparator to unconsciousness on Day 1 of treatment

• Bispectral index value (BISx)

  Every 5 minutes from admission of a patient to the operating room until transfer from the operating room on Day 1 of treatment

• TIMEDOB

  From the end of administration of the test drug/comparator to the time when the patient will be able to say the date of his/her birth on Day 1 and 2 of treatment

Other Outcomes (2)

• Number of blood pressure measurement points with systolic blood pressure ≤ 50 mm Hg and ≥ 180 mm Hg

  During the surgery

• Number of patients needed vasopressor use

  During the surgery

Study Arms (2)

Remimazolam

EXPERIMENTAL

The induction of anesthesia: intravenous infusion of 6 mg/kg/h until registration of loss of consciousness. Maintenance of anesthesia: Remimazolam intravenous infusion initiated at a dose of 1 mg/kg/h; the dose level was adjusted accordingly based on a systemic patient monitoring until the end of operation to 2 mg/kg/h maximum; In case of loss of consciousness was not registered in 2.5 minutes of continuous intravenous infusion: drug administration was terminated. If loss of consciousness was not registered during 30 seconds, other sedative drugs were used for induction and maintenance of anesthesia. In case of signs of awakening (fluctuation of blood pressure/heart rate, lacrimation, sweating, etc.) were observed: intravenous bolus infusion (maximum level of 12 mg/kg/h for 1 minute). If signs of awakening remained remimazolam administration was discontinued and other sedatives were used.

Drug: Remimazolam; Drug: Fentanyl; Drug: Rocuronium bromide

Propofol

ACTIVE COMPARATOR

The induction of anesthesia: intravenous infusion of 1.5-2.5 mg/kg for about 1 minute. Maintenance of anesthesia: intravenous infusion for a total dose of 4-12 mg/kg/h; the dose level was adjusted accordingly based on a systemic patient monitoring until the end of operation. In case of loss of consciousness was not registered other sedative drugs were used for induction and maintenance of anesthesia. In case of signs of awakening (fluctuation of blood pressure/heart rate, lacrimation, sweating, etc.) were observed and propofol dose adjustment had not resulted in the desired effect and signs of awakening were saved: the use of propofol was discontinued and other sedatives were used.

Drug: Propofol; Drug: Fentanyl; Drug: Rocuronium bromide

Interventions

Remimazolam DRUG

Lyophilisate for preparation of solution for intravenous administration, 50 mg. Required to prepare a 50 ml syringe with the infusion solution at a concentration of 1 mg/ml (in accordance with guidance given in protocol)

Remimazolam

Propofol DRUG

Emulsion for infusion, 10 mg/mL in 20-mL glass vials

Also known as: Diprivan®

Propofol

Fentanyl DRUG

Solution for intravenous administration, 50 mg/mL. Used for anesthesia induction (at a dose of 2 mg/kg) and, if necessary, anesthesia maintenance (the dose was selected individually)

Propofol; Remimazolam

Rocuronium bromide DRUG

Solution for intravenous administration, 10 mg/mL. Used for anesthesia induction (at a dose of 0.6-0.9 mg/kg) and, if necessary, anesthesia maintenance (the dose was selected individually)

Propofol; Remimazolam

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form to participate in the study prior to initiation of any study-related procedures, and possibility to follow the protocol.
• Body mass index (BMI) calculated as body weight (kg)/height (m)2, ≤ 30 kg/m2.
• Patients hospitalized for elective surgery in whom intraoperative mechanical ventilation using tracheal intubation (oropharyngeal or nasotracheal) is planned.
• Patients for whom the duration of inpatient hospital stay for at least 2 days (1 day before and 1 day after the surgery).
• American Society of Anesthesiologists scale (ASA) I - II functional class.
• For females: negative result of a pregnancy test (urine test using test strips) since the moment of enrollment to the study prior to administration of the test drug/reference drug, as well as consent to use birth control methods throughout the entire study (since the moment of enrollment to the study until the complete ending of the observation period) for women of childbearing potential.
• Female patients who did not have menstrual periods for 2 years or more before enrollment to the study or female patients who underwent a surgical procedure (surgical sterilization, bilateral oophorectomy, hysterectomy etc.) are considered females of no childbearing potential.
• For males: consent to use birth control methods throughout the entire study (since the moment of enrollment to the study until the complete ending of the observation period).

You may not qualify if:

• Patients in whom local anesthesia is planned (subarachnoid (spinal) block, epidural anesthesia or peripheral nerve block) during the period from admission into an operating room till extubation on Day 1 (administration of the test drug/reference drug).
• Patients in whom organ transplantation is planned.
• Patients in whom heart surgery is planned.
• Patients with uncontrolled hypertension (e.g. systolic blood pressure ≥160 mm Hg while on antihypertensive therapy).
• Patients in whom total bilirubin level ≥ 51 mmol/l or aspartate aminotransferase (AST) or alanin aminotransferase (ALT) level ≥ 2.5 upper limit of normal (ULN) (or ≥100 U/L) during the period from Day -14 till their admission to the operating room.
• Patients in whom serum creatinine level ≥140 mmol/l during the period from Day -14 till their admission to the operating room.
• Patients undergoing an urgent surgical procedure.
• Patients in whom a surgical procedure lasting less than 1 hour is planned.
• Patients in whom extubation problems are anticipated due to the expected necessity of prolonged respiratory support using tracheal intubation.
• Patients with history of resistance to benzodiazepines or propofol.
• Patients with history of hypersensitivity to benzodiazepines, propofol, opioid analgesics, fentanyl citrate, rocuronium bromide, sugammadex sodium, flumazenil, naloxone, or other anesthetics or benzodiazepine receptor antagonists.
• Acute open-angle glaucoma.
• Myasthenia gravis or myasthenic syndrome.
• Patients with shock or coma.
• Acute alcohol intoxication.

Sponsors & Collaborators

• R-Pharm: lead
• Synergy Research Inc.: collaborator

Study Sites (6)

FSBI Central Clinical Hospital and Polyclinic of Adminisatration of the President of the Russian Federation

Moscow, Russia

Location

FSBI Russian National Medical and Surgical Center n.a. N.I.Pirogov

Moscow, Russia

Location

SBHI City Clinical Hospital №1 n.a. N.I. Pirogov

Moscow, Russia

Location

SBHI City Clinical Hospital №64 n.a. V.V. Vinogradov

Moscow, Russia

Location

SBHI Institute of Surgery n.a. A.V.Vishevsky

Moscow, Russia

Location

SBHI Moscow Clinical Research and Practical center of Department of Healthcare of the city of Moscow

Moscow, Russia

Location

MeSH Terms

Interventions

remimazolam; Propofol; Fentanyl; Rocuronium

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Simple blinding stipulates hiding the treatment group for a patient. In addition, the research team had a blinded anesthesiologist who did not know about a patient's therapy group throughout the trial. This anesthesiologist assessed a patient's condition by scales (modified Aldrete score, memory assessment, postoperative delirium diagnosis). Anesthesia depth assessment by bispectral index (BIS), administration and, if necessary, correction of the trial drug/reference drug dosage were carried out by another anesthesiologist.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2018
• First Posted: September 13, 2018
• Study Start: August 22, 2017
• Primary Completion: May 15, 2018
• Study Completion: May 24, 2018
• Last Updated: September 13, 2018

Record last verified: 2018-09

Locations

RU (6)