A Phase 3 interventional study of Remimazolam and Propofol in General Anaesthesia, sponsored by R-Pharm. Completed at 6 sites in Russian Federation. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-09-13.
Sponsored by R-Pharm · Phase 3, Interventional, and Treatment
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.
Only patients with scheduled operations were screened for eligibility in this study. Screening period for each patient lasted from 1 to 14 days. All patients eligible as per protocol criteria were randomized in 1:1 ratio to receive investigational or reference drug. Randomisation was carried out in admission to the operating room - Day1.
For the induction of anesthesia, first there was administration of the trial drug / reference drug, then - administration of a narcotic analgesic (fentanyl at a dose of 2 mg/kg), after which after loss of consciousness, muscle relaxant was used (rocuronium bromide at a dose of 0.6-0.9 mg/kg). Tracheal intubation was performed after achieving the necessary relaxation of the muscles.
Maintenance of anesthesia during surgery was done using the trial drug / reference drug, muscle relaxant (rocuronium bromide - if necessary, during the anesthesia maintenance, the dose was selected individually) and narcotic analgetic (fentanyl, if necessary, during the anesthesia maintenance, the dose was selected individually). To control patient's condition before, during and after surgery, the significant vital parameters were monitored (level of blood pressure and heart rate, respiratory rate, body temperature, saturation, intraoperative ECG, bispectral index (BIS)).
After the operation patients were transferred to the postoperation room where the assessment of the operation memory, and possible presence of postoperative delirium was performed as well as on Day 2. Further treatment and determination of compliance of patient's condition with the criteria for discharge from the hospital was carried out in accordance with current practice of the center.
In 7 (± 2) days after the end of trial drugs administration, patient's condition monitoring and safety evaluation were carried out through telephone contact with the patient, during which data on adverse events and concomitant therapy were collected. Scheduled trial duration for each patient was a maximum of 24 days.
Therapy was considered ineffective, if other sedatives were required for induction (loss of consciousness was not registered after study drugs dose adjustment) and/or maintenance of the required level of sedation during anesthesia (in case of signs of awakening appeared and remained after study drugs dose adjustment).
Therapy efficacy evaluation was based on primary and secondary efficacy criteria. Effect of general anesthetic, a combined evaluation criterion consisted of the following criteria. The trial drug/reference drug was regarded effective in patients who had not had any of the below criteria and ineffective in patients who had at least one of the below criteria:
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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.
Exclusion Criteria:
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
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
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)
Emulsion for infusion, 10 mg/mL in 20-mL glass vials
Also known as: Diprivan®
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)
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)
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.
Time frame: During the surgery and 24 hours after the study drugs administration
TIMEextub
Extubation time (minutes)
Time frame: 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
Time of eyes opening (minutes). A patient was often asked with a normal voice to open his/her eyes. The time to spontaneous eye opening was recorded.
Time frame: From the moment of discontinuation of the test drug / comparator to eye opening on Day 1 of treatment
TIMEunconsc
Time of unconsciousness
Time frame: From the onset of administration of the test drug/comparator to unconsciousness on Day 1 of treatment
Bispectral index value (BISx)
Bispectral index calculation was carried out automatically by the hardware monitor on electrical activity of the brain and could range from 0 (no electrical activity of the brain) to 100 (clear conscience)
Time frame: Every 5 minutes from admission of a patient to the operating room until transfer from the operating room on Day 1 of treatment
TIMEDOB
Date of birth memory
Time frame: 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
TIMEORleave
Operation room leaving time - the time when a patient's condition meets the criteria for transfer from the operating room
Time frame: From the end of administration of the test drug/comparator to the time when the patient is transferred from the operating room on Day 1 of treatment
TIMErecuper
Total recovery time assessed by the modified Aldrete scale - a commonly used scale (0-10 points) for determining when patients can be safely discharged from the post-anesthesia care unit assessing patient's activity, respiration, circulation, consciousness and oxygen saturation.
Time frame: From the end of administration of the study drug/comparator until the patient reaches the modified Aldrete's system score of ≥9 points on Day 1 of treatment
Number of blood pressure measurement points with systolic blood pressure ≤ 50 mm Hg and ≥ 180 mm Hg
Time frame: During the surgery
Number of patients needed vasopressor use
Number of patients developed hypotension during the operation required treatment with vasopressors
Time frame: During the surgery
This study is completed, as verified in Sep 2018. You cannot join it, but the record below documents what was studied.
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