Back to resultsRifaximin for Infection Prophylaxis in Hematopoietic Stem Cell Transplantation
Primary Purpose
Microbial Colonization
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rifaximin
Sponsored by
About this trial
This is an interventional treatment trial for Microbial Colonization focused on measuring Rifaximin, Microbiome, Allogeneic hematopoietic stem cell transplantation, Blood stream infections, Acute graft versus host disease
Eligibility Criteria
Inclusion Criteria:
- Allogeneic HSCT recipients between the ages of 2 and 21 years.
- Underlying hematologic malignancy, regardless of donor type or graft source.
- Myeloablative conditioning regimen.
Exclusion Criteria:
- Known hypersensitivity to rifaximin, or other rifamycin antimicrobial agents.
- Minimally toxic conditioning regimen (e.g. low dose TBI based). Since these regimens induce minimal myelosuppression and gut injury, patients receiving them probably stand little to gain from antibiotic prophylaxis.
- Patients with ongoing bacterial, viral or fungal active infections are not eligible for this study. Patients who remain on broad spectrum antibiotics for the treatment of a previous infection are not eligible.
- The use of prophylactic antibiotics is not permitted.
- Following the standard practice in blood and marrow transplantation, pregnant or breast feeding patients will be excluded
Sites / Locations
- Children's Healthcare of Atlanta
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Rifaximin
Retrospective comparison cohort
Arm Description
Rifaximin will be administered twice a day orally or by nasogastric tube to patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).
Thirty six patients who underwent HSCT for hematologic malignancies, and received myeloablative conditioning, without prophylactic antibiotics, between 2013-2017 enrolled in the Aflac biorepository will comprise the comparison arm. Clinical data on transplant and infection characteristics is available and linked to stool microbiome samples already analyzed and described. Stored plasma and peripheral blood mononuclear cells are available for further analysis.
Outcomes
Primary Outcome Measures
Alterations to microbiome diversity in children treated with rifaximin compared to the historical cohort.
Composition will be assessed using 16S RNA sequencing. The Shannon index will be calculated for quantification of bacterial diversity.
Secondary Outcome Measures
Rates of BSI pathogen infection/colonization frequency during the treatment period compared to the historical cohort.
Results of the GI pathogen panel, a test incorporated into routine patient care detecting DNA or RNA of 22 common viral, bacterial, and parasitic organisms, will provide a second assessment through molecular detection of the presence of common organisms associated with intestinal dysbiosis.
Transplant related mortality (TRM)
Number of deaths occurring in continuous complete remission.
Number of patients with Acute GVHD
Early onset (before day 100) acute GVHD (including all grades, and stratified by grades) will be assessed according to the Blood and Marrow Transplant Clinical Trials Network Manual version 2, 2005, section 1 using the NIH consensus criteria
Number of patients with Chronic GVHD including overlap syndrome
Chronic GVHD including overlap syndrome, will be assessed according to the 2014 NIH consensus criteria.
Number of patients with other Infections
Other Infections will be defined in accordance with the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures
Number of patients with relapse free survival at 1 year
Survival without relapse of underlying malignancy.
Overall number of patients survived at 1 year
Survival with or without relapse of underlying malignancy.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03529825
Brief Title
Rifaximin for Infection Prophylaxis in Hematopoietic Stem Cell Transplantation
Official Title
Rifaximin for Infection Prophylaxis in Hematopoietic Stem Cell Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
July 18, 2018 (Actual)
Primary Completion Date
October 19, 2020 (Actual)
Study Completion Date
September 10, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Primary purpose of the study is to see if rifaximin can improve the balance of bacteria within the gut, which has been shown to improve transplant outcomes. It will also assess whether rifaximin can reduce the risk of infection in blood/marrow transplant (BMT).
Detailed Description
This study is for patients who will be having a blood/marrow transplant (BMT) to treat leukemia, lymphoma or other cancer of the blood. The blood or marrow cells will come from another person (donor)-allogeneic BMT. Bacterial infections and acute graft versus host disease (AGVHD) are frequent complications of allogeneic BMT. Bacterial infections sometimes happen because injury to the gut during transplant allows gut bacteria to cross the injured gut barrier and get to the blood. AGVHD happens when certain white blood cells, called T-cells, in the donor cells (the graft) attack the patient's body.
Primary purpose of the study is to see if rifaximin can improve the balance of bacteria within the gut, which has been shown to improve transplant outcomes. It will also assess whether rifaximin can reduce the risk of infection in blood/marrow transplant (BMT).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Microbial Colonization
Keywords
Rifaximin, Microbiome, Allogeneic hematopoietic stem cell transplantation, Blood stream infections, Acute graft versus host disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Pilot, single arm prospective study with retrospective control arm
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rifaximin
Arm Type
Experimental
Arm Description
Rifaximin will be administered twice a day orally or by nasogastric tube to patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).
Arm Title
Retrospective comparison cohort
Arm Type
No Intervention
Arm Description
Thirty six patients who underwent HSCT for hematologic malignancies, and received myeloablative conditioning, without prophylactic antibiotics, between 2013-2017 enrolled in the Aflac biorepository will comprise the comparison arm. Clinical data on transplant and infection characteristics is available and linked to stool microbiome samples already analyzed and described. Stored plasma and peripheral blood mononuclear cells are available for further analysis.
Intervention Type
Drug
Intervention Name(s)
Rifaximin
Intervention Description
Rifaximin will be administered twice a day orally or by nasogastric tube, at a dose of 15 mg/kg divided BID with a maximum dose of 1,650 mg, day -7 to day +28 or discharge (maximum duration 36 days).
Primary Outcome Measure Information:
Title
Alterations to microbiome diversity in children treated with rifaximin compared to the historical cohort.
Description
Composition will be assessed using 16S RNA sequencing. The Shannon index will be calculated for quantification of bacterial diversity.
Time Frame
Period between the start of the preparative regimen and day 28 post transplant
Secondary Outcome Measure Information:
Title
Rates of BSI pathogen infection/colonization frequency during the treatment period compared to the historical cohort.
Description
Results of the GI pathogen panel, a test incorporated into routine patient care detecting DNA or RNA of 22 common viral, bacterial, and parasitic organisms, will provide a second assessment through molecular detection of the presence of common organisms associated with intestinal dysbiosis.
Time Frame
Period between the start of the preparative regimen and day 28 post transplant
Title
Transplant related mortality (TRM)
Description
Number of deaths occurring in continuous complete remission.
Time Frame
Period between the start of the preparative regimen and day 28 post transplant
Title
Number of patients with Acute GVHD
Description
Early onset (before day 100) acute GVHD (including all grades, and stratified by grades) will be assessed according to the Blood and Marrow Transplant Clinical Trials Network Manual version 2, 2005, section 1 using the NIH consensus criteria
Time Frame
Period between the start of the preparative regimen and day 100 post transplant
Title
Number of patients with Chronic GVHD including overlap syndrome
Description
Chronic GVHD including overlap syndrome, will be assessed according to the 2014 NIH consensus criteria.
Time Frame
Period between the start of the preparative regimen and year 5 post-transplant.
Title
Number of patients with other Infections
Description
Other Infections will be defined in accordance with the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures
Time Frame
Period between the start of the preparative regimen and day 28 post transplant
Title
Number of patients with relapse free survival at 1 year
Description
Survival without relapse of underlying malignancy.
Time Frame
Period between the start of the preparative regimen and year 1 post-transplant.
Title
Overall number of patients survived at 1 year
Description
Survival with or without relapse of underlying malignancy.
Time Frame
Period between the start of the preparative regimen and year 1 post-transplant.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Allogeneic HSCT recipients between the ages of 2 and 21 years.
Underlying hematologic malignancy, regardless of donor type or graft source.
Myeloablative conditioning regimen.
Exclusion Criteria:
Known hypersensitivity to rifaximin, or other rifamycin antimicrobial agents.
Minimally toxic conditioning regimen (e.g. low dose TBI based). Since these regimens induce minimal myelosuppression and gut injury, patients receiving them probably stand little to gain from antibiotic prophylaxis.
Patients with ongoing bacterial, viral or fungal active infections are not eligible for this study. Patients who remain on broad spectrum antibiotics for the treatment of a previous infection are not eligible.
The use of prophylactic antibiotics is not permitted.
Following the standard practice in blood and marrow transplantation, pregnant or breast feeding patients will be excluded
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Muna Qayed, MD MSc
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Rifaximin for Infection Prophylaxis in Hematopoietic Stem Cell Transplantation
We'll reach out to this number within 24 hrs