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Impact of Remimazolam on Prognosis After Bladder Cancer Surgery

Sponsor
Peking University First Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04532606
Collaborator
Beijing Tsinghua Chang Gung Hospital (Other), Navy General Hospital, Beijing (Other), Guizhou Provincial People's Hospital (Other), Jiangsu Provincial People's Hospital (Other), Shanghai 10th People's Hospital (Other)
1,128
Enrollment
6
Locations
2
Arms
31.8
Anticipated Duration (Months)
188
Patients Per Site
5.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
1128 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Impact of Remimazolam Tosilate for General Anesthesia on Prognosis After Bladder Cancer Surgery: a Randomized Controlled Trial
Actual Study Start Date :
Feb 5, 2021
Anticipated Primary Completion Date :
Oct 1, 2022
Anticipated Study Completion Date :
Oct 1, 2023

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of emergence delirium (early). [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.

    2. Recurrence-free survival (long-term). [Up to 3 years after surgery.]

      Time from surgery to recurrence/metastasis or all-cause death, whichever come first.

    Secondary Outcome Measures

    1. Incidence of postoperative delirium (early). [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.

    2. Incidence of postoperative nausea and vomiting (early). [Up to 24 hours after surgery.]

      Incidence of postoperative nausea and vomiting.

    3. Incidence of intraoperative awareness (early). [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?

    4. Length of stay in hospital after surgery (early). [Up to 30 days after surgery.]

      Length of stay in hospital after surgery.

    5. Incidence of non-delirium complications (early). [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.

    6. All-cause 30-day mortality (early). [Up to 30 days after surgery.]

      All-cause 30-day mortality.

    7. Overall survival (long-term). [Up to 3 years after surgery.]

      Time from surgery to all-cause death.

    8. Event-free survival (long-term). [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.

    9. Health related quality of life of 1-year survivors (long-term). [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.

    Other Outcome Measures

    1. Intensity of pain (early). [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).

    2. Subjective sleep quality (early). [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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Beijing Tsinghua Chang Gung Hospital Beijing Beijing China
    2 The Sixth Medical Center of PLA General Hospital Beijing Beijing China
    3 Peking University First Hospital Beijin Bejing China 100034
    4 Guizhou Provincial People's Hospital Guiyang Guizhou China
    5 Jiangsu Provincial People's Hospital Nanjing Jiangsu China
    6 Shanghai 10th People's Hospital Shanghai Shanghai China

    Sponsors and Collaborators

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

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Dong-Xin Wang, Professor, Peking University First Hospital
    ClinicalTrials.gov Identifier:
    NCT04532606
    Other Study ID Numbers:
    • 2020-212
    First Posted:
    Aug 31, 2020
    Last Update Posted:
    Jul 12, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Dong-Xin Wang, Professor, Peking University First Hospital
    Remimazolam
    Bladder Cancer
    Surgery
    Emergence Delirium
    Recurrence-free Survival
    Additional relevant MeSH terms:
    Urinary Bladder Neoplasms
    Delirium
    Recurrence
    Anesthetics
    Propofol

    Study Results

    No Results Posted as of Jul 12, 2021