Choosing the Best Antibiotic to Protect Friendly Gut Bacteria During the Course of Stem Cell Transplant

Rational Use of Broad-spectrum Antibiotics as Empiric Antibiotic Therapy in Febrile Neutropenia in Recipients of Allogeneic Hematopoietic Cell Transplantation

The purpose of this study is to see how different antibiotics affect the community of friendly bacteria existing in the intestinal tract (gut). Under normal circumstances, these friendly bacteria are not harmful and they help with normal bodily functions such as digestion. When these bacteria are absent, several complications may occur, such as infections with harmful bacteria or other inflammatory reactions, that can complicate the stem cell transplant course. Treatment with antibiotics or chemotherapy is known to kill off these friendly bacteria. In this study we compare the effects of different antibiotics on the community of friendly bacteria in the gut. For microbiota-related biomarker analysis, optional urine samples (MSKCC patients only) will be collected at baseline, 7 +/-2 days after initiation of antibiotic therapy, and on post-transplant days +28, +56 and +100 (+/- 7days).

Study Overview

• Status: Recruiting
• Conditions: Febrile Neutropenia; Intestinal Microbiome
• Intervention / Treatment: Drug: Piperacillin-tazobactam; Drug: cefepime

• Study Type: Interventional
• Enrollment (Estimated): 460
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Boglarka Gyurkocza, MD; Phone Number: 212-639-2860; Email: ABMTTrials@mskcc.org
• Study Contact Backup: Name: Susan Seo, MD; Email: ABMTTrials@mskcc.org

Study Locations

• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack Meridian Health
      • Contact: Michele Donato, MD; Phone Number: 551-996-8297
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Susan Seo, MD; Email: ABMTTrials@mskcc.org
      • Contact: Boglarka Gyurkocza, MD; Email: ABMTTrials@mskcc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Patients with any hematologic malignancy undergoing

Exclusion Criteria:

• Patients with severe allergies to piperacillin-tazobactam, cefepime, aztreonam or vancomycin. Severe reactions include anaphylaxis and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).
• Patients with unconfirmed allergies to piperacillin-tazobactam, cefepime, aztreonam or vancomycin can be evaluated by an Allergy/Immunology specialist, after which they may become eligible by a consensus of the treating physician, trial investigator and and the Allery
• Prolonged antibiotic treatment ( ≥10 days, within 3 weeks of enrollment) as prevention or suppression of an ongoing infection, where treatment involves gut-perturbing anti anaerobic antibiotics
• Patients with history of infection with extended-spectrum beta-lactamase producing organism. Patients known to be colonized with multi-drug resistant gram-negative organisms or with history of infection with multi-drug resistant organisms will be evaluated case by case and discussed with infectious disease specialist before enrollment
• Febrile patients
• Patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Piperacillin-tazobactam	Drug: Piperacillin-tazobactam; piperacillin-tazobactam (4.5 gm IV q 6 hrs)
Experimental: cefepime	Drug: cefepime; (2 gm IV q 8 hrs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measurement of fold-change in Clostridiales abundance	Fold change will be assessed 7 +/- 2 days after initiating antibiotic treatment for febrile neutropenia and will be compared to the pre-treatment specimen. Pre-treatment stool specimen will be collected between the time of enrollment Patients will be enrolled and infusion of allografts or first episode of neutropenic fever, whichever occurs first.	7 +/- 2 days after initiation of piperacillin-tazobactam or cefepime

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Boglarka Gyurkocza, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2017
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: March 8, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Antibiotic; piperacillin-tazobactam; aztreonam; cefepime; 17-097
• Additional Relevant MeSH Terms: Wounds and Injuries; Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Body Temperature Changes; Heat Stress Disorders; Neutropenia; Hyperthermia; Fever; Febrile Neutropenia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination; Cefepime
• Other Study ID Numbers: 17-097

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes