Impact of Remimazolam on Prognosis After Bladder Cancer Surgery

Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04532606
• Other study ID #: 2020-212
• Status: Recruiting
• Phase: Phase 4
• Start date: February 5, 2021
• Est. completion date: October 2025

Study information

• Verified date: July 2023
• Source: Peking University First Hospital
• Contact: Wang Dong-Xin, MD, PhD
• Phone: 86 10 83572784
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1128
• Est. completion date: October 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Benzodiazepines
• Bladder Cancer
• Cancer Recurrence
• Delirium
• Recurrence
• Surgery
• Urinary Bladder Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijin	Bejing
China	Beijing Tsinghua Chang Gung Hospital	Beijing	Beijing
China	The Sixth Medical Center of PLA General Hospital	Beijing	Beijing
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	Jiangsu Provincial People's Hospital	Nanjing	Jiangsu
China	Shanghai 10th People's Hospital	Shanghai	Shanghai

Sponsors (6)

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

Country where clinical trial is conducted

China, 

References & Publications (32)

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* Note: There are 32 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Intensity of pain (early).	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.
Other	Subjective sleep quality (early).	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
Primary	Incidence of emergence delirium (early).	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.
Primary	Recurrence-free survival (long-term).	Time from surgery to recurrence/metastasis or all-cause death, whichever come first.	Up to 3 years after surgery.
Secondary	Incidence of postoperative delirium (early).	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.
Secondary	Incidence of postoperative nausea and vomiting (early).	Incidence of postoperative nausea and vomiting.	Up to 24 hours after surgery.
Secondary	Incidence of intraoperative awareness (early).	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.
Secondary	Length of stay in hospital after surgery (early).	Length of stay in hospital after surgery.	Up to 30 days after surgery.
Secondary	Incidence of non-delirium complications (early).	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.
Secondary	All-cause 30-day mortality (early).	All-cause 30-day mortality.	Up to 30 days after surgery.
Secondary	Overall survival (long-term).	Time from surgery to all-cause death.	Up to 3 years after surgery.
Secondary	Event-free survival (long-term).	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.
Secondary	Health related quality of life of 1-year survivors (long-term).	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.