Impact of Remimazolam Tosilate for General Anesthesia on Prognosis After Bladder Cancer Surgery: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 1,128
- 试验地点
- 6
- 主要终点
- Incidence of emergence delirium (early).
研究概览
简要总结
Bladder cancer is one of the most common genitourinary cancers. Transurethral resection of bladder tumor (TURBT) is the standard therapy for nonmuscle invasive bladder cancer. However, patients after TURBT are at risk for recurrence and progression. Benzodiazepines are proved to inhibit proliferation of multiple types of cancer cells in vitro. Delirium is an acute onset and transient cerebral dysfunction and is associated with worse outcomes. Previous studies indicated that benzodiazepines increase incidence of postoperative delirium. Remimazolam is a new benzodiazepine with rapid onset and ultra-short activity. The aims of this study are to explore the impact of remimazolam for general anesthesia on emergency delirium and recurrence-free survival in patients undergoing bladder cancer surgery.
详细描述
Bladder cancer is one of the most common genitourinary cancers. Approximately 70-80% of bladder cancers are nonmuscle invasive, including those of Ta-T1 stage and carcinoma in situ. Transurethral resection of bladder tumor (TURBT) is the standard therapy for nonmuscle invasive bladder cancer. However, patients after TURBT are at a high risk of recurrence and progression.
Recently, impacts of anesthetic agents on tumor cells have attracted more attention. Benzodiazepines are found to inhibit proliferation of lymphoma, neural tumor, lung cancer, rectal cancer and breast cancer cells in vitro. Midazolam may have anti-tumor effects through induction of apoptosis and inhibition of inflammatory reaction. However, clinical evidence regarding effects of benzodiazepines on outcomes after cancer surgery remains lacking.
Remimazolam is a new benzodiazepine with rapid onset and ultra-short activity. It is rapidly metabolized by tissue esterases to inactive metabolite and can be reversed by flumazenil. Therefore, patients wake up rapidly even after prolonged infusions. It is also found to produce less respiratory and circulatory depression when compared with propofol.
Delirium is an acute onset and transient cerebral dysfunction, and is associated with worse outcomes including prolonged hospitalization, worse functional recovery, cognitive decline, and increased mortality rate. Previous studies indicated that benzodiazepines increase incidence of postoperative delirium, possibly due to prolonged action. With the property of ultra-short activity, remimazolam may not increase the incidence of delirium. But evidence is lacking in this aspect.
The aims of this study are to explore the impact of remimazolam on emergency delirium and recurrence-free survival in patients undergoing bladder cancer surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥50 years and <90 years;
- •Preoperative diagnosis is non-muscle-invasive bladder cancer(Ta-T1);
- •Scheduled to undergo transurethral resection of bladder tumor;
- •Agree to participate, and provide written informed consent.
排除标准
- •Refuse to participate;
- •Emergent surgery;
- •Combined with other malignant tumors;
- •Use of benzodiazepines for 1 week within the last month before surgery;
- •Preoperative history of schizophrenia, epilepsy, parkinsonism or myasthenia gravis;
- •Inability to communicate in the preoperative period due to coma, profound dementia, language barrier, or end-stage disease;
- •Critical illness (preoperative American Society of Anesthesiologists physical status classification ≥IV), severe hepatic dysfunction (Child-Pugh class C), or severe renal dysfunction (undergoing dialysis before surgery);
- •The purpose of surgery is to make a diagnosis or preoperative judgement is that tumor cannot be completely removed.
研究组 & 干预措施
Remimazolam group
Remimazolam is administered intravenously for anesthesia induction and maintenance. The dose and infusion rate is adjusted to maintain Bispectral Index (BIS) value between 40 and 60. Analgesia is maintained with remifentanil and/or sufentanil. Muscle relaxation is maintained with rocuronium and/or cisatracurium. Sevoflurane inhalation is provided when considered necessary.
干预措施: Remimazolam (Drug)
Propofol group
Propofol is administered intravenously for anesthesia induction and maintenance. The dose and infusion rate is adjusted to maintain BIS value between 40 and 60. Analgesia is maintained with remifentanil and/or sufentanil. Muscle relaxation is maintained with rocuronium and/or cisatracurium. Sevoflurane inhalation is provided when considered necessary.
干预措施: Propofol (Drug)
结局指标
主要结局
Incidence of emergence delirium (early).
时间窗: Up to 2 hours during the stay in post-anesthesia care unit after surgery.
Emergence delirium is assessed with the Confusion Assessment Method for the Intensive Care Unit at 10 and 30 minutes after admission to the post-anesthesia care unit after surgery.
Recurrence-free survival (long-term).
时间窗: Up to 3 years after surgery.
Time from surgery to recurrence/metastasis or all-cause death, whichever come first.
次要结局
- All-cause 30-day mortality (early).(Up to 30 days after surgery.)
- Overall survival (long-term).(Up to 3 years after surgery.)
- Incidence of postoperative delirium (early).(During the first 3 days after surgery.)
- Incidence of postoperative nausea and vomiting (early).(Up to 24 hours after surgery.)
- Health related quality of life of 1-year survivors (long-term).(At the end of the 1st year after surgery.)
- Length of stay in hospital after surgery (early).(Up to 30 days after surgery.)
- Incidence of non-delirium complications (early).(Up to 30 days after surgery.)
- Incidence of intraoperative awareness (early).(Up to 1 day after surgery.)
- Event-free survival (long-term).(Up to 3 years after surgery.)
研究者
Dong-Xin Wang
Professor
Peking University First Hospital