Multicentral Preventive Antibiotics With Cystectomy Within Enhanced Recovery After Surgery

Phase 3

• Conditions: Bladder Cancer
• Interventions: Drug: Amoxicillin+clavulanic acid 1200 mg or Cefuroksim 1500mg; Drug: Meropenem 1000 mg

• Registration Number: NCT05392634
• Lead Sponsor: N.N. Petrov National Medical Research Center of Oncology

Brief Summary

The current usage of antibiotic prophylaxis (AP) in radical cystectomy (RC) is aimed to reducing the incidence of surgical site infections and incidence of unnecessary prescribing of antibiotics. There are a huge number of different AP protocols according to Urological Associations. However, there is no convincing evidence to support variations and duration of AP which requires a randomized clinical trial on AP when performing variants of RC with uroderivation.

Research hypothesis: The use of prolonged antibiotic prophylaxis (5 days), depending on the glomerular filtration rate, does not affect the incidence of postoperative complications.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-02
• Status Verified: 2022-05
• Study First Submitted: 2022-05-22
• Study First Submitted QC: 2022-05-22
• Last Update Submitted: 2022-05-25
• Study First Posted: 2022-05-26
• Last Update Posted: 2022-05-31
• Primary Completion: 2023-02-02
• Study Completion: 2023-11-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

• histologically confirmed diagnosis of very high risk non muscle-invasive bladder carcinoma (cT1NoMo) or muscle-invasive bladder carcinoma (cT2-T4NxM0) with or without neoadjuvant therapy (chemotherapy or immunotherapy are both possible);
• patient should be eligible for radical cystectomy (RC) + pelvic lymph node dissection (PLND), and agreement to undergo curative intent standard RC + PLND (including prostatectomy or hysterectomy if applicable) according to surgeon opinion;
• pelvic lymph node dissection is engaged in two possible variants: extended level to intersection of ureter and iliac vessels; superextended level - up to aortic bifurcation;
• urinary diversion is engaged in two possible variants: orthotopic diversion (J- or U-pouch reservoirs), heterotopic diversion in the Mainz-I modification, Bricker;
• male or female is at least 18 years old at the time of signing the informed consent form;
• female patient is eligible to participate if she is not pregnant, not breastfeeding;
• ECOG performance status of 0 or 1;
• adequate organ function (in accordance with laboratory standards);
• used valid protocol for Enhanced Recovery After Surgery (ERAS protocol) at Hospital (oncourological department);

Exclusion Criteria

• known additional non-urothelial malignancy that is progressing or has required active anticancer treatment ≤3 years of study randomization, with certain exceptions;

• diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug;

• replacement doses of corticosteroids are permitted for participants with adrenal insufficiency;

• evidences of uncontrolled diseases (diabetes mellites, noninfectious pneumonitis that required steroids, et.) or any conditions which interfere with the conduct of the research procedures according to doctor opinion;

• presence of 2 or more criteria for systemic inflammatory response syndrome (SIRS) at the time of the patient's admission to the hospital (assessment of these factors 3-7 days before randomization):

  • temperature ≥ 38˚С or ≤ 36˚С;
  • heart rate (HR) ≥ 90 / min;
  • respiratory rate < 20/min or hyperventilation (Pa CO2 ≤ 32 mm Hg);
  • blood leukocytes >12 ∙ 109 / l or < 4 ∙ 109 / l, or immature forms > 10%

• prohibited urinary diversion when planning surgery and signing voluntary consent: diversion into continuous intestine (ureterosigmostomy, Mainz-pouch II operation);

• inadequate organ function:

  • Neutrophils <1.5 x 10 ^ 9 / l
  • Platelets <100 x 10 ^ 9 / l
  • ALT> 3 x VGN
  • AST> 3 x VGN
  • Bilirubin> 1.5 x ULN
  • GFR level <35 ml / min

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Amoxicillin/ Cefuroksim	Amoxicillin+clavulanic acid 1200 mg or Cefuroksim 1500mg	standard antibiotic prophylaxis 24 hours
Meropenem	Meropenem 1000 mg	preventive antibiotic therapy within 5 days from the date of the skin incision

Primary Outcome Measures

Name	Time	Method
Event rate	90 days after Radical cystectomy	Determine the frequency of events of clinical interest in the period 30-90 days after RC in a surgical hospital working according to the protocol for early postoperative recovery of the patient
Event-free survival	90 days after Radical cystectomy	Estimate the time to development of events of clinical interest in the period 30-90 days after RC in a surgical hospital

Secondary Outcome Measures

Name	Time	Method
All-cause mortality	90 days after Radical cystectomy	Establish the frequency of 30-day, 90-day all-cause mortality after RC in a surgical hospital working according to the protocol for early postoperative patient recovery
Emergence of resistant	30-90 days after Radical cystectomy	To assess the probability of occurrence of acquired carbapenemase against the background of prolonged antibiotic prophylaxis

Trial Locations

Locations (1)

FSBI "N.N. Petrov NMRC of oncology" MH of Russian Federation; 🇷🇺 Saint Petersburg, Санкт-Петербург, Russian Federation