Multicentral Preventive Antibiotics With Cystectomy Within Enhanced Recovery After Surgery

NCT05392634 | Unknown Phase 3 DMC

• 1 other identifier: MACS-1
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

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.

Conditions

Bladder Cancer

Keywords

radical cystectomy; antibiotic prophylaxis; ERAS protocol; muscle-invasive bladder cancer; urinary diversion

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Emergence of resistant

  30-90 days after Radical cystectomy

• All-cause mortality

  90 days after Radical cystectomy

Study Arms (2)

Amoxicillin/ Cefuroksim

ACTIVE COMPARATOR

standard antibiotic prophylaxis 24 hours

Drug: Amoxicillin+clavulanic acid 1200 mg or Cefuroksim 1500mg

Meropenem

EXPERIMENTAL

preventive antibiotic therapy within 5 days from the date of the skin incision

Drug: Meropenem 1000 mg

Interventions

Meropenem 1000 mg DRUG

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.

Meropenem

Amoxicillin+clavulanic acid 1200 mg or Cefuroksim 1500mg DRUG

Group A: antibiotic prophylaxis within 24 hours from the moment of skin incision according to local clinical practice;

Amoxicillin/ Cefuroksim

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);

You may not qualify if:

• 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

Sponsors & Collaborators

• N.N. Petrov National Medical Research Center of Oncology: lead
• The Foundation for Cancer Research Support (RakFond): collaborator

Study Sites (1)

FSBI "N.N. Petrov NMRC of oncology" MH of Russian Federation

Saint Petersburg, Sankt-Peterburg, 197758, Russia

RECRUITING

Related Publications (1)

• Berkut MV, Belyaev AM, Galunova TY, Tyapkin NI, Reva SA, Nosov AK. Prolonged 120-h meropenem antibiotic prophylaxis in radical cystectomy compared to 24h standard antibiotic prophylaxis: Final analysis of the randomized clinical trial. Arab J Urol. 2024 Jul 3;22(4):235-242. doi: 10.1080/20905998.2024.2373399. eCollection 2024.

  PMID: 39355793 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Meropenem; Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Mariya Berkut, PhD

  FSBI "N.N. Petrov NMRC of oncology" MH of Russian Federation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mariya Berkut, PhD

CONTACT

+79312870497; berkutv91@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 22, 2022
• First Posted: May 26, 2022
• Study Start: February 2, 2022
• Primary Completion: February 2, 2023
• Study Completion: November 1, 2023
• Last Updated: May 31, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)