Multicentral Preventive Antibiotics With Cystectomy Within Enhanced Recovery After Surgery

Study Overview
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Brief Summary
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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.

Official Title
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Рrospective Multicenter Randomized 3 Phase Study Evaluating the Role of Prolonged Antibiotic Prophylaxis as a Measure to Reduce the Incidence of Postoperative Complications After Radical Cystectomy With ERAS Protocol

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: Meropenem 1000 mg
* Drug: Amoxicillin+clavulanic acid 1200 mg or Cefuroksim 1500mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amoxicillin/ Cefuroksim<br>standard antibiotic prophylaxis 24 hours | Drug: Amoxicillin+clavulanic acid 1200 mg or Cefuroksim 1500mg<br>* Group A: antibiotic prophylaxis within 24 hours from the moment of skin incision according to local clinical practice;<br>|
| Experimental: Meropenem<br>preventive antibiotic therapy within 5 days from the date of the skin incision | Drug: Meropenem 1000 mg<br>* Group B: prolonged antibiotic prophylaxis >72 hours (5 days) from the moment of the skin incision in accordance with the selected clinic drug + correction of the appointment based on clinical events after 5 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event rate | 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 | 90 days after Radical cystectomy | 
| Event-free survival | Estimate the time to development of events of clinical interest in the period 30-90 days after RC in a surgical hospital | 90 days after Radical cystectomy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Emergence of resistant | To assess the probability of occurrence of acquired carbapenemase against the background of prolonged antibiotic prophylaxis | 30-90 days after Radical cystectomy | 
| All-cause mortality | 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 | 90 days after Radical cystectomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radical cystectomy, antibiotic prophylaxis, ERAS protocol, muscle-invasive bladder cancer, urinary diversion