Multicentral Preventive Antibiotics With Cystectomy Within Enhanced Recovery After Surgery (MACS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Amoxicillin+clavulanic acid 1200 mg or Cefuroksim 1500mg; Drug: Meropenem 1000 mg

• Study Type: Interventional
• Enrollment (Anticipated): 98
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mariya Berkut, PhD; Phone Number: +79312870497; Email: berkutv91@gmail.com

Study Locations

• Russian Federation
  • Санкт-Петербург
    • Saint Petersburg, Санкт-Петербург, Russian Federation, 197758
      • Recruiting
      • FSBI "N.N. Petrov NMRC of oncology" MH of Russian Federation
      • Contact: Mariya Berkut, PhD; Phone Number: 89312870497; Email: berkutv91@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Amoxicillin/ Cefuroksim; standard antibiotic prophylaxis 24 hours	Drug: Amoxicillin+clavulanic acid 1200 mg or Cefuroksim 1500mg; Group A: antibiotic prophylaxis within 24 hours from the moment of skin incision according to local clinical practice;
Experimental: Meropenem; preventive antibiotic therapy within 5 days from the date of the skin incision	Drug: Meropenem 1000 mg; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: N.N. Petrov National Medical Research Center of Oncology
• Collaborators: The Foundation for Cancer Research Support (RakFond)
• Investigators: Principal Investigator: Mariya Berkut, PhD, FSBI "N.N. Petrov NMRC of oncology" MH of Russian Federation

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2022
• Primary Completion (Anticipated): February 2, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: May 22, 2022
• First Submitted That Met QC Criteria: May 22, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 25, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: radical cystectomy; antibiotic prophylaxis; ERAS protocol; muscle-invasive bladder cancer; urinary diversion
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Meropenem; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: MACS-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No