Impact of Remimazolam on Prognosis After Bladder Cancer Surgery

July 29, 2025 updated by: Dong-Xin Wang, Peking University First Hospital

Impact of Remimazolam Tosilate for General Anesthesia on Prognosis After Bladder Cancer Surgery: a Randomized Controlled Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

1128

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Recruiting
        • Beijing Tsinghua Chang Gung Hospital
        • Contact:
          • Huan Zhang, MD
      • Beijing, Beijing, China
        • Recruiting
        • The Sixth Medical Center of PLA General Hospital
        • Contact:
          • Jun Li, MD
    • Bejing
      • Beijin, Bejing, China, 100034
    • Guizhou
      • Guiyang, Guizhou, China
        • Recruiting
        • Guizhou Provincial People's Hospital
        • Contact:
          • Fang-Xiang Zhang, MD
    • Jiangsu
      • Nanjing, Jiangsu, China
        • Recruiting
        • Jiangsu Provincial People's Hospital
        • Contact:
          • Cun-Ming Liu, MD
    • Shanghai
      • Shanghai, Shanghai, China
        • Recruiting
        • Shanghai 10th People's Hospital
        • Contact:
          • Xuan Zhao, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥50 years and <90 years;
  2. Preoperative diagnosis is non-muscle-invasive bladder cancer(Ta-T1);
  3. Scheduled to undergo transurethral resection of bladder tumor;
  4. Agree to participate, and provide written informed consent.

Exclusion Criteria:

  1. Refuse to participate;
  2. Emergent surgery;
  3. Combined with other malignant tumors;
  4. Use of benzodiazepines for 1 week within the last month before surgery;
  5. Preoperative history of schizophrenia, epilepsy, parkinsonism or myasthenia gravis;
  6. Inability to communicate in the preoperative period due to coma, profound dementia, language barrier, or end-stage disease;
  7. 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);
  8. The purpose of surgery is to make a diagnosis or preoperative judgement is that tumor cannot be completely removed.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Remimazolam
Remimazolam 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.
Other Names:
  • Remimazolam anesthesia
Active Comparator: 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.
Drug: Propofol
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 is provided when considered necessary.
Other Names:
  • Propofol anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of emergence delirium (early).
Time Frame: 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.
Up to 2 hours during the stay in post-anesthesia care unit after surgery.
Recurrence-free survival (long-term).
Time Frame: Up to 3 years after surgery.
Time from surgery to recurrence/metastasis or all-cause death, whichever come first.
Up to 3 years after surgery.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of postoperative delirium (early).
Time Frame: During the first 3 days after surgery.
Delirium is assessed twice daily with the Chinese version of the 3-minute diagnostic interview for Confusion Assessment Method-defined delirium.
During the first 3 days after surgery.
Incidence of postoperative nausea and vomiting (early).
Time Frame: Up to 24 hours after surgery.
Incidence of postoperative nausea and vomiting.
Up to 24 hours after surgery.
Incidence of intraoperative awareness (early).
Time Frame: Up to 1 day after surgery.
Intraoperative awareness is assessed with modified Brice interview before discharge from the post-anesthesia care unit and on the 1st day after surgery. The interview included five questions: (1) What was the last thing you remembered happening before you went to sleep? (2) What is the first thing you remember after your operation? (3) Can you remember anything in between? (4) Can you remember if you had any dreams during your operation? (5) What was the worst thing about your operation?
Up to 1 day after surgery.
Length of stay in hospital after surgery (early).
Time Frame: Up to 30 days after surgery.
Length of stay in hospital after surgery.
Up to 30 days after surgery.
Incidence of non-delirium complications (early).
Time Frame: Up to 30 days after surgery.
Non-delirium complications are defined as newly occurred medical conditions other than delirium that are harmful for patients' recovery and required therapeutic intervention, i.e., grade 2 or higher on Clavien-Dindo classification.
Up to 30 days after surgery.
All-cause 30-day mortality (early).
Time Frame: Up to 30 days after surgery.
All-cause 30-day mortality.
Up to 30 days after surgery.
Overall survival (long-term).
Time Frame: Up to 3 years after surgery.
Time from surgery to all-cause death.
Up to 3 years after surgery.
Event-free survival (long-term).
Time Frame: Up to 3 years after surgery.
Time from surgery to serious events, cancer recurrence/metastasis, or all-cause death, whichever come first. Serious events are defined as any new onset disease that required hospitalization and/or surgical intervention.
Up to 3 years after surgery.
Health related quality of life of 1-year survivors (long-term).
Time Frame: At the end of the 1st year after surgery.
Health related quality of life is assessed with the World Health Organization Quality of Life-brief version (WHOQOL-BREF) which is a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.
At the end of the 1st year after surgery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intensity of pain (early).
Time Frame: During the first 3 days after surgery.
Assessed twice daily (8-10 am and 18-20 pm) with the Numeric Rating Scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain).
During the first 3 days after surgery.
Subjective sleep quality (early).
Time Frame: During the first 3 days after surgery
Assessed in the morning (8-10 am) with the Numeric Rating Scale (NRS; an 11-point scale where 0=the best sleep and 10=the worst sleep).
During the first 3 days after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Collaborators

Shanghai 10th People's Hospital
Beijing Tsinghua Chang Gung Hospital
Guizhou Provincial People's Hospital
Navy General Hospital, Beijing
Jiangsu Provincial People's Hospital

Investigators

  • Principal Investigator: Wang Dong-Xin, MD, PhD, Peking University First Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 5, 2021

Primary Completion (Estimated)

October 1, 2025

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

August 25, 2020

First Submitted That Met QC Criteria

August 27, 2020

First Posted (Actual)

August 31, 2020

Study Record Updates

Last Update Posted (Actual)

July 30, 2025

Last Update Submitted That Met QC Criteria

July 29, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-212

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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