REmimazolam vs Propofol Total Intravenous Anesthesia on Outcomes After Major Noncardiac SurgEry

Study Overview
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Brief Summary
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The goal of this randomized controlled trial is to compare total intravenous anesthesia with remimazolam vs total intravenous anesthesia with propofol in moderate-to-high risk patients undergoing major elective noncardiac surgery under general anesthesia. The primary hypothesis is that total intravenous anesthesia with remimazolam can increase days alive and out of hospital at postoperative day 30 compared with total intravenous anesthesia with propofol.

Official Title
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REmimazolam vs Propofol Total Intravenous Anesthesia on Outcomes After Major Noncardiac SurgEry (REPOSE-2): A Multicenter Randomized Controlled Trial

Conditions
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Anesthesia, Surgery-Complications

Intervention / Treatment
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* Drug: Remimazolam
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥45 years; Undergoing elective major surgery under general anesthesia (expected surgery time >2 h, expected length of postoperative stay >2 d); Fulfilling ≥1 of the following criteria: history of coronary artery disease; history of stroke; history of congestive heart failure; preoperative NT-proBNP >200 pg/mL or BNP>92 pg/mL; age ≥70 years; diabetes requiring medical treatment; ASA status 3 or 4; history of chronic kidney disease (preoperative sCr >133 μmol/L or 1.5 mg/dL); history of peripheral arterial disease; preoperative serum albumin <30 g/L; preoperative hemoglobin <100 g/L. Exclusion Criteria: Undergoing organ transplantation, cardiac, craniocerebral, burn or interventional operations; Low risk or minor surgery End-stage renal disease requiring renal-replacement therapy; Hepatic dysfunction (Child B or C); Previous liver or kidney transplantation; Previous allergy to general anesthetics; Unable to receive bispectral index monitoring; ASA score ≥5; Exposure to general anesthesia in prior 30 days or anticipated re-exposure to general anesthesia within 30 days after surgery; Need for prolonged airway protection or mechanical ventilatory support after surgery; Current participation in another interventional study; Previous participation in this study; Pregnant or breastfeeding women.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam TIVA<br>Remimazolam is administered at 6-12 mg/kg/h intravenously for anesthesia induction and at 1.0-2.0 mg/kg/h for maintenance of general anesthesia. The dose is titrated to maintain Bispectral Index value between 40 and 60. | Drug: Remimazolam<br>* Remimazolam is administered intravenously for induction and maintenance of general anesthesia.<br>|
| Active Comparator: Propofol TIVA<br>Propofol 1.5-2.5mg/kg is administered intravenously for anesthesia induction and propofol at 4-12mg/kg/h is used for maintenance of general anesthesia. The dose is titrated to maintain Bispectral Index value between 40 and 60. | Drug: Propofol<br>* Propofol is administered intravenously for induction and maintenance of general anesthesia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days alive and out of hospital at day 30 | Number of days alive and out of hospital | 30 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause 30-day mortality | Number of patients who die of any cause | 30 days after randomization | 
| Length of hospital stay | Number of days in hospital | 30 days after randomization | 
| Unplanned re-hospitalization | Number of patients who experience unplanned hospital re-admissions | 30 days after randomization | 
| Postoperative complications | Number of patients who experience postoperative complications | 30 days after randomization | 
| Quality of Recovery-15 score on the first day after surgery | Using Quality of Recovery-15 questionnaire to evaluate the quality of perioperative recovery. Quality of Recovery-15 consists of 15 comprehensive questions, including physical comfort (5 items), psychological support (2 items), physical independence (2 items), emotional state (4 items), and pain (2 items), each item is scored with 0-10 points, 0 represents poor state, 10 represents good state, and the total score is the Quality of Recovery-15 score of the patient. | Postoperative day 1 |