Effect of Remimazolam Versus Propofol on Early Postoperative Quality of Recovery in Patients Undergoing Cytoreductive Surgery for Peritoneal Surface Malignancies: A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 320
- 试验地点
- 1
- 主要终点
- Quality of Recovery-15 total score at 48 hours
研究概览
简要总结
The REPAIR Trial is a single-center, prospective, randomized, parallel-group superiority trial enrolling 320 adults scheduled for elective cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Participants will be assigned 1:1 to bispectral index-guided remimazolam- or propofol-based general anesthesia under standardized perioperative care. The primary objective is to determine whether remimazolam improves patient-reported recovery 48 ± 4 hours after surgery, measured by the Chinese 15-item Quality of Recovery score (QoR-15; range, 0 to 150; higher scores indicate better recovery). The investigators hypothesize that remimazolam will produce a higher 48-hour QoR-15 score than propofol. Secondary outcomes will characterize recovery at 24 and 72 hours, intraoperative hypotension burden and vasopressor use, acute kidney injury, infection, delirium, respiratory complications, other safety events, and 30-day mortality.
详细描述
Cytoreductive surgery for peritoneal surface malignancies often involves extensive peritoneal stripping, multivisceral resection, major fluid shifts, and prolonged anesthesia. Some patients also receive HIPEC. Propofol may cause vasodilation and cardiovascular depression, whereas remimazolam may provide greater hemodynamic stability. Whether this difference translates into clinically meaningful improvement in overall postoperative recovery remains uncertain.
After written informed consent and completion of baseline assessments, eligible participants will be randomized 1:1 using variable block sizes of 4, 6, or 8, stratified by whether HIPEC is planned. Allocation will be obtained from a permission-controlled electronic randomization system after eligibility is reconfirmed in the operating room and immediately before the first assigned study hypnotic. Participants, postoperative QoR-15 assessors, complication adjudicators, and the primary statistician will remain masked. Anesthesia clinicians cannot be masked because they must titrate the assigned drug.
Both groups will receive bispectral index-guided total intravenous anesthesia with a target BIS of 40 to 60 and standardized principles for analgesia, hemodynamic rescue, temperature management, neuromuscular monitoring, extubation, and intensive care. Surgery end is defined as completion of skin closure, and all postoperative assessment windows are anchored to that time.
The primary outcome is the Chinese QoR-15 total score 48 ± 4 hours after surgery. The primary analysis will use analysis of covariance or an equivalent general linear model with treatment group, baseline QoR-15 score, and planned HIPEC stratum as covariates. The adjusted between-group mean difference, 95% confidence interval, and two-sided P value will be reported. The sample size of 320 provides 90% power to detect a 6-point difference assuming a common standard deviation of 15 and allowing 15% for an unavailable primary outcome or loss to follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.Age 18 to 75 years. 2.American Society of Anesthesiologists physical status class II or III. 3.Pathologically confirmed primary peritoneal surface malignancy or peritoneal metastasis from colorectal, gastric, ovarian, or appendiceal malignancy.
- •4.Scheduled for elective cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy under general anesthesia.
- •5.Expected surgical duration of at least 2 hours and planned postoperative admission to the intensive care unit.
- •6.Able to understand and independently complete the Chinese Quality of Recovery-15 questionnaire.
- •7.Willing to participate and able to provide written informed consent.
排除标准
- •Emergency surgery.
- •Uncontrolled bacterial, fungal, or viral infection requiring systemic anti-infective treatment within 14 days before surgery, or temperature of 38.0 °C or higher at post-consent eligibility confirmation with corresponding clinical, imaging, microbiological, or laboratory evidence. Perioperative antimicrobial prophylaxis is not an exclusion.
- •Child-Pugh class C, total bilirubin greater than 3 times the upper limit of normal, or alanine or aspartate aminotransferase greater than 5 times the upper limit of normal.
- •Estimated glomerular filtration rate below 30 mL/min/1.73 m² or maintenance renal replacement therapy.
- •Known allergy to remimazolam, benzodiazepines, propofol, or their excipients, or a contraindication to either study drug.
- •Continuous or near-daily opioid use for at least 90 days before surgery, or benzodiazepine or Z-drug use on at least 5 days per week for at least 4 weeks.
- •Severe cognitive, psychiatric, hearing, speech, or language impairment that prevents understanding and independent completion of the QoR-15 after standardized explanation.
- •Pregnancy or breastfeeding.
- •A preoperative plan for continuous epidural analgesia or another continuous regional analgesic technique that is incompatible with the study's standardized intravenous analgesia pathway.
- •A specific clinical condition that, in the investigator's judgment, would make participation pose an unacceptable risk.
结局指标
主要结局
Quality of Recovery-15 total score at 48 hours
时间窗: 48 ± 4 hours after the end of surgery, defined as completion of skin closure (allowable window, 44 to 52 hours)
The validated Chinese QoR-15 contains 15 items scored from 0 to 10. The total score ranges from 0 to 150, with higher scores indicating better recovery. The first valid assessment within the prespecified window is used. If any item cannot be completed, the total score is missing rather than prorated. Participants who die before the assessment window are not assigned a score of zero; mortality is reported separately and addressed in prespecified sensitivity analyses.
次要结局
- Lowest intraoperative mean arterial pressure(From initiation of the assigned study hypnotic until completion of skin closure during the index surgery.)
- Proportion of valid monitoring time with mean arterial pressure below 65 mmHg(From initiation of the assigned study hypnotic until completion of skin closure during the index surgery)
- Quality of Recovery-15 total score at 24 hours(24 ± 2 hours after completion of skin closure (allowable window, 22 to 26 hours))
- Cumulative duration of mean arterial pressure below 65 mmHg(From initiation of the assigned study hypnotic until completion of skin closure during the index surgery)
- Time-weighted average of mean arterial pressure below 65 mmHg(From initiation of the assigned study hypnotic until completion of skin closure during the index surgery)
- Quality of Recovery-15 total score at 72 hours(72 ± 6 hours after completion of skin closure (allowable window, 66 to 78 hours))
- Time to first vasopressor administration(From initiation of the assigned study hypnotic until completion of skin closure during the index surgery.)
- Cumulative dose of vasopressors(From initiation of the assigned study hypnotic until completion of skin closure during the index surgery.)
- Maximum vasopressor infusion rate(From initiation of the assigned study hypnotic until completion of skin closure during the index surgery.)
- Number of hypotension rescue episodes(From initiation of the assigned study hypnotic until completion of skin closure during the index surgery.)
- Number of study-hypnotic dose reductions due to hypotension(From initiation of the assigned study hypnotic until completion of skin closure during the index surgery)
- Incidence of acute kidney injury(From completion of skin closure through postoperative day 7 or hospital discharge, whichever occurs first.)
- Incidence of postoperative infection(Within 30 days after completion of skin closure)
- Incidence of postoperative delirium(Postoperative days 1 to 3 or until transfer out of the ICU, whichever occurs first.)
- Incidence of postoperative hypoxemia(Within 7 days after completion of skin closure)
- Use of noninvasive ventilation(Within 7 days after completion of skin closure.)
- Use of high-flow nasal cannula oxygen(Within 7 days after completion of skin closure)
- Incidence of respiratory failure(Within 7 days after completion of skin closure)
- Incidence of reintubation(Within 7 days after the first planned extubation)
- Incidence of pneumonia(Within 7 days after completion of skin closure)
- Incidence of bradycardia(From the first dose of assigned study hypnotic through postoperative day 30)
- Incidence of study-drug allergic reactions(From the first dose of assigned study hypnotic through postoperative day 30)
- Incidence of serious adverse events(From the first dose of assigned study hypnotic through postoperative day 30)
- All-cause mortality(Within 30 days after completion of skin closure)
研究者
Duanyi
Senior Anesthesiologist
Beijing Tsinghua Chang Gung Hospital