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BenzodiazepinesPhase 4NCT04532606

Impact of Remimazolam on Prognosis After Bladder Cancer Surgery

A Phase 4 study testing Remimazolam and Propofol in people with Benzodiazepines and Bladder Cancer, run by Peking University First Hospital at 6 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 50 to 90 years
Conditions the study is for
Benzodiazepines, Bladder Cancer, Delirium
What is being tested?
Remimazolam and Propofol
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,128 participants
Where
6 sitesChina
Study dates
5 Feb 2021to Oct 2026
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Wang Dong-Xin, MD, PhD contact

86 10 83572784

wangdongxin@hotmail.com

Zhang Yu-Xiu, MD contact

+86 15201190755

zhangyuxiu1992@163.com

6 sites in 1 country

China6 sites, 6 recruiting

  • Peking University First Hospital

    Beijin, Bejing, 100034

    Wang Dong-Xin, MD, PhD, 86(10) 83572784, wangdongxin@hotmail.com

    Zhang Yu-Xiu, MD, +86 15201190755, zhangyuxiu1992@163.com

    Recruiting

  • Beijing Tsinghua Chang Gung Hospital

    Beijing, Beijing Municipality

    Huan Zhang, MD

    Recruiting

  • The Sixth Medical Center of PLA General Hospital

    Beijing, Beijing Municipality

    Jun Li, MD

    Recruiting

  • Guizhou Provincial People's Hospital

    Guiyang, Guizhou

    Fang-Xiang Zhang, MD

    Recruiting

  • Jiangsu Provincial People's Hospital

    Nanjing, Jiangsu

    Cun-Ming Liu, MD

    Recruiting

  • Shanghai 10th People's Hospital

    Shanghai, Shanghai Municipality

    Xuan Zhao, MD

    Recruiting

Other trials in China

About this study

Official title: 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.

Read the 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.

Being tested
Remimazolam, Propofol
Keywords
Remimazolam, Bladder Cancer, Surgery, Emergence Delirium, Recurrence-free Survival
Medical subject headings
Urinary Bladder Neoplasms, Delirium, Emergence Delirium

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RemimazolamDrug

    Also called Remimazolam anesthesia

    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.

  • PropofolDrug

    Also called Propofol anesthesia

    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.

Study groups in NCT04532606
Study groupRoleWhat they receive
Remimazolam groupExperimentalRemimazolam 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.
Receives: Drug: Remimazolam
Propofol groupActive comparatorPropofol 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.
Receives: Drug: Propofol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 2 hours during the stay in post-anesthesia care unit after surgery.

  2. Recurrence-free survival (long-term).

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

    Measured: Up to 3 years after surgery.

Secondary outcomes (9)

  1. 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.

    Measured: During the first 3 days after surgery.

  2. Incidence of postoperative nausea and vomiting (early).

    Incidence of postoperative nausea and vomiting.

    Measured: Up to 24 hours after surgery.

  3. 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?

    Measured: Up to 1 day after surgery.

  4. Length of stay in hospital after surgery (early).

    Length of stay in hospital after surgery.

    Measured: Up to 30 days after surgery.

  5. 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.

    Measured: Up to 30 days after surgery.

  6. All-cause 30-day mortality (early).

    All-cause 30-day mortality.

    Measured: Up to 30 days after surgery.

  7. Overall survival (long-term).

    Time from surgery to all-cause death.

    Measured: Up to 3 years after surgery.

  8. 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.

    Measured: Up to 3 years after surgery.

  9. 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.

    Measured: At the end of the 1st year after surgery.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2020
  2. Study start5 Feb 2021
  3. Primary completionOct 2025 (estimated)
  4. Study completionOct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
1,128 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04532606
Sponsor's protocol ID
2020-212
Status last verified
Jul 2025
First submitted
25 Aug 2020
Last updated
30 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chen W, Zheng R, Zhang S, Zeng H, Xia C, Zuo T, Yang Z, Zou X, He J. Cancer incidence and mortality in China, 2013. Cancer Lett. 2017 Aug 10;401:63-71. doi: 10.1016/j.canlet.2017.04.024. Epub 2017 May 3.

    PubMed 28476483

  • Babjuk M, Bohle A, Burger M, Capoun O, Cohen D, Comperat EM, Hernandez V, Kaasinen E, Palou J, Roupret M, van Rhijn BWG, Shariat SF, Soukup V, Sylvester RJ, Zigeuner R. EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. 2017 Mar;71(3):447-461. doi: 10.1016/j.eururo.2016.05.041. Epub 2016 Jun 17.

    PubMed 27324428

  • Soukup V, Capoun O, Cohen D, Hernandez V, Babjuk M, Burger M, Comperat E, Gontero P, Lam T, MacLennan S, Mostafid AH, Palou J, van Rhijn BWG, Roupret M, Shariat SF, Sylvester R, Yuan Y, Zigeuner R. Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non-muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review. Eur Urol. 2017 Nov;72(5):801-813. doi: 10.1016/j.eururo.2017.04.015. Epub 2017 Apr 28.

    PubMed 28457661

  • Allard P, Bernard P, Fradet Y, Tetu B. The early clinical course of primary Ta and T1 bladder cancer: a proposed prognostic index. Br J Urol. 1998 May;81(5):692-8. doi: 10.1046/j.1464-410x.1998.00628.x.

    PubMed 9634043

  • Holmgren L, O'Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995 Feb;1(2):149-53. doi: 10.1038/nm0295-149.

    PubMed 7585012

  • Hofer SO, Molema G, Hermens RA, Wanebo HJ, Reichner JS, Hoekstra HJ. The effect of surgical wounding on tumour development. Eur J Surg Oncol. 1999 Jun;25(3):231-43. doi: 10.1053/ejso.1998.0634.

    PubMed 10336800

  • Eggermont AM, Steller EP, Marquet RL, Jeekel J, Sugarbaker PH. Local regional promotion of tumor growth after abdominal surgery is dominant over immunotherapy with interleukin-2 and lymphokine activated killer cells. Cancer Detect Prev. 1988;12(1-6):421-9.

    PubMed 3263198

  • Stevens MF, Werdehausen R, Gaza N, Hermanns H, Kremer D, Bauer I, Kury P, Hollmann MW, Braun S. Midazolam activates the intrinsic pathway of apoptosis independent of benzodiazepine and death receptor signaling. Reg Anesth Pain Med. 2011 Jul-Aug;36(4):343-9. doi: 10.1097/AAP.0b013e318217a6c7.

    PubMed 21701267

  • Wang C, Datoo T, Zhao H, Wu L, Date A, Jiang C, Sanders RD, Wang G, Bevan C, Ma D. Midazolam and Dexmedetomidine Affect Neuroglioma and Lung Carcinoma Cell Biology In Vitro and In Vivo. Anesthesiology. 2018 Nov;129(5):1000-1014. doi: 10.1097/ALN.0000000000002401.

    PubMed 30157038

  • Mishra SK, Kang JH, Lee CW, Oh SH, Ryu JS, Bae YS, Kim HM. Midazolam induces cellular apoptosis in human cancer cells and inhibits tumor growth in xenograft mice. Mol Cells. 2013 Sep;36(3):219-26. doi: 10.1007/s10059-013-0050-9. Epub 2013 Sep 2.

    PubMed 24008365

  • Beinlich A, Strohmeier R, Kaufmann M, Kuhl H. Specific binding of benzodiazepines to human breast cancer cell lines. Life Sci. 1999;65(20):2099-108. doi: 10.1016/s0024-3205(99)00475-0.

    PubMed 10579463

  • Barends CRM, Absalom AR, Struys MMRF. Drug selection for ambulatory procedural sedation. Curr Opin Anaesthesiol. 2018 Dec;31(6):673-678. doi: 10.1097/ACO.0000000000000652.

    PubMed 30124543

  • Cornett EM, Novitch MB, Brunk AJ, Davidson KS, Menard BL, Urman RD, Kaye AD. New benzodiazepines for sedation. Best Pract Res Clin Anaesthesiol. 2018 Jun;32(2):149-164. doi: 10.1016/j.bpa.2018.06.007. Epub 2018 Jul 3.

    PubMed 30322456

  • Goudra BG, Singh PM. Remimazolam: The future of its sedative potential. Saudi J Anaesth. 2014 Jul;8(3):388-91. doi: 10.4103/1658-354X.136627.

    PubMed 25191193

  • Ilic RG. Fospropofol and remimazolam. Int Anesthesiol Clin. 2015 Spring;53(2):76-90. doi: 10.1097/AIA.0000000000000053. No abstract available.

    PubMed 25807020

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Remimazolam and Propofol in people with Benzodiazepines and Bladder Cancer, run by Peking University First Hospital at 6 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Wang Dong-Xin, MD, PhD (86 10 83572784, wangdongxin@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of emergence delirium (early). (time frame: Up to 2 hours during the stay in post-anesthesia care unit after surgery.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04532606, which also lists 32 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2025.

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