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Vancomycin for C Difficile NAAT+/EIA- Hematology Oncology Patients

Primary Purpose

Clostridium Difficile Infection, Hematologic Diseases, Bone Marrow Transplant

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vancomycin Oral Capsule
Placebo Oral Capsule
Sponsored by
Medical College of Wisconsin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clostridium Difficile Infection focused on measuring microbiome, bone marrow transplantation, Clostridium difficile, metabolomics, vancomycin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients admitted to the hematology oncology inpatient units at Froedtert Memorial Lutheran Hospital
  • New onset of diarrhea during hospitalization
  • C. difficile clinical testing showing NAAT positive EIA negative results

Exclusion Criteria:

  • Being unable to consent for self
  • Inability to take enteral medications
  • Unwillingness to enroll in study
  • Patient has a documented allergy to vancomycin
  • Patient has a documented life expectancy shorter than treatment course (14 days)
  • Patient is unwilling or unable to provide stool samples in the outpatient setting after discharge
  • Diagnosis of C. difficile colitis [NAAT (+) and toxin EIA (+) within 3 months of enrollment).
  • New onset of abdominal distention within 24 hours prior to the onset of diarrhea during index admission
  • Presence of toxic megacolon
  • Presence of clinical sepsis. Sepsis will be defined as a Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more as per 2016 definitions
  • Pregnancy or lactating

Sites / Locations

  • Froedtert and the Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Vancomycin treated group

Placebo group

Arm Description

This group will be given vancomycin oral capsules, 125 mg, every 6 hours, for 14 days.

This group will be given placebo oral capsules every 6 hours for 14 days.

Outcomes

Primary Outcome Measures

Changes in Clostridium difficile bacterial loads in the stool
Changes in Clostridium difficile bacterial counts from stool as determined by quantitative polymerase chain reaction (PCR)

Secondary Outcome Measures

Full Information

First Posted
January 19, 2017
Last Updated
September 8, 2020
Sponsor
Medical College of Wisconsin
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1. Study Identification

Unique Protocol Identification Number
NCT03030248
Brief Title
Vancomycin for C Difficile NAAT+/EIA- Hematology Oncology Patients
Official Title
Randomized Double Blind Controlled Trial for the Treatment of Nucleic Acid Amplification Test (NAAT)+/Toxin Enzyme Immunoassay (EIA)- Clostridium Difficile in the Hematology Oncology Population
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
June 1, 2018 (Actual)
Primary Completion Date
June 30, 2020 (Actual)
Study Completion Date
June 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will randomized hematology oncology patients with active diarrhea and a NAAT positive/toxin EIA negative to either 14 days of oral vancomycin capsules or placebo. The study is designed to include 30 patients (15 per arm). Outcomes will include C. difficile load using qPCR, VRE loads, structural and functional microbiome changes and frequency of bowel movements. All endpoints will be measured at several time points including days 0, 14, 21 and 90.
Detailed Description
The adverse health consequences resulting from antibiotic overtreatment of NAAT(+), toxin(-) patients may be particularly important in transplant recipients. The usual treatment prescribed for CDI at the Froedtert Memorial Lutheran Hospital is oral vancomycin. While this drug has excellent activity against C. difficile and commonly suppresses its growth to non-detection, it does not eradicate carriage and its use results in marked and prolonged disruption of the lower intestinal microbiota. Meanwhile, the degree of lower intestinal microbiota disruption at the time of HSCT engraftment has been demonstrated to be an independent predictor (controlling for other markers of underlying disease) of overall and transplant-related 3-year mortality.14 In addition, recent findings suggest that bone marrow suppressive effects of antibiotics, in this case potentially unnecessary oral vancomycin (which is not appreciably absorbed), may be solely mediated via microbiota disruption. All these data supports the notion that antibiotic treatment of NAAT(+), toxin(-) C. difficile patients might have significant negative repercussions without a clear clinical benefit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile Infection, Hematologic Diseases, Bone Marrow Transplant, Oncologic Disorders
Keywords
microbiome, bone marrow transplantation, Clostridium difficile, metabolomics, vancomycin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Patients will be divided into two groups, one receiving oral vancomycin capsules, the other receiving oral placebo capsules.
Masking
ParticipantCare ProviderInvestigator
Masking Description
The allocation status of patients within this study will be held in sealed envelopes by the unblinded research pharmacist on the team. Neither the main care provider, study physicians, or the patient will know of their group, until either the end of the study (after data analysis). We will also have a blinded pharmacist.
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vancomycin treated group
Arm Type
Active Comparator
Arm Description
This group will be given vancomycin oral capsules, 125 mg, every 6 hours, for 14 days.
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
This group will be given placebo oral capsules every 6 hours for 14 days.
Intervention Type
Drug
Intervention Name(s)
Vancomycin Oral Capsule
Other Intervention Name(s)
Vancocin hydrochloride Oral Capsule
Intervention Description
We have chosen oral vancomycin capsules as it is currently a standard of care for Clostridium difficile infections, is poorly absorbed by the intestines, and is easier to blind compared to oral vancomycin solution.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Capsule
Intervention Description
A capsule containing gelatin, polyethylene glycol, titanium dioxide, iron oxide, and FD&C blue No. 2. Contains the inactive ingredients of the vancomycin oral capsule, as mixed by the Froedtert Health Research Pharmacy.
Primary Outcome Measure Information:
Title
Changes in Clostridium difficile bacterial loads in the stool
Description
Changes in Clostridium difficile bacterial counts from stool as determined by quantitative polymerase chain reaction (PCR)
Time Frame
Pre-treatment, 1, 7, 14, 21, 28, and 90 days past the beginning of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients admitted to the hematology oncology inpatient units at Froedtert Memorial Lutheran Hospital New onset of diarrhea during hospitalization C. difficile clinical testing showing NAAT positive EIA negative results Exclusion Criteria: Being unable to consent for self Inability to take enteral medications Unwillingness to enroll in study Patient has a documented allergy to vancomycin Patient has a documented life expectancy shorter than treatment course (14 days) Patient is unwilling or unable to provide stool samples in the outpatient setting after discharge Diagnosis of C. difficile colitis [NAAT (+) and toxin EIA (+) within 3 months of enrollment). New onset of abdominal distention within 24 hours prior to the onset of diarrhea during index admission Presence of toxic megacolon Presence of clinical sepsis. Sepsis will be defined as a Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more as per 2016 definitions Pregnancy or lactating
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Silvia Munoz-Price, M.D., Ph.D.
Organizational Affiliation
Medical College of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Froedtert and the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Participant data to be shared would consist of age categories, genders, treatment groups, Clostridium difficile status, microbiome profile and metabolic profile. The data will be anonymized to prevent the identification of individual patients from the data provided. The data would be made available through contacting the principal investigator directly.
Citations:
PubMed Identifier
26061850
Citation
Lessa FC, Winston LG, McDonald LC; Emerging Infections Program C. difficile Surveillance Team. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Jun 11;372(24):2369-70. doi: 10.1056/NEJMc1505190. No abstract available.
Results Reference
background
PubMed Identifier
26956066
Citation
Martin JS, Monaghan TM, Wilcox MH. Clostridium difficile infection: epidemiology, diagnosis and understanding transmission. Nat Rev Gastroenterol Hepatol. 2016 Apr;13(4):206-16. doi: 10.1038/nrgastro.2016.25. Epub 2016 Mar 9.
Results Reference
background
PubMed Identifier
24445449
Citation
Theriot CM, Koenigsknecht MJ, Carlson PE Jr, Hatton GE, Nelson AM, Li B, Huffnagle GB, Z Li J, Young VB. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun. 2014;5:3114. doi: 10.1038/ncomms4114.
Results Reference
background
PubMed Identifier
27239562
Citation
Theriot CM, Bowman AA, Young VB. Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine. mSphere. 2016 Jan 6;1(1):e00045-15. doi: 10.1128/mSphere.00045-15. eCollection 2016 Jan-Feb.
Results Reference
background
PubMed Identifier
19929371
Citation
Sethi AK, Al-Nassir WN, Nerandzic MM, Bobulsky GS, Donskey CJ. Persistence of skin contamination and environmental shedding of Clostridium difficile during and after treatment of C. difficile infection. Infect Control Hosp Epidemiol. 2010 Jan;31(1):21-7. doi: 10.1086/649016.
Results Reference
background
PubMed Identifier
27943501
Citation
Aldrete SD, Kraft CS, Magee MJ, Chan A, Hutcherson D, Langston AA, Greenwell BI, Burd EM, Friedman-Moraco R. Risk factors and epidemiology of Clostridium difficile infection in hematopoietic stem cell transplant recipients during the peritransplant period. Transpl Infect Dis. 2017 Feb;19(1). doi: 10.1111/tid.12649.
Results Reference
result
PubMed Identifier
27707993
Citation
Isaac S, Scher JU, Djukovic A, Jimenez N, Littman DR, Abramson SB, Pamer EG, Ubeda C. Short- and long-term effects of oral vancomycin on the human intestinal microbiota. J Antimicrob Chemother. 2017 Jan;72(1):128-136. doi: 10.1093/jac/dkw383. Epub 2016 Oct 5.
Results Reference
result
PubMed Identifier
26348734
Citation
Polage CR, Gyorke CE, Kennedy MA, Leslie JL, Chin DL, Wang S, Nguyen HH, Huang B, Tang YW, Lee LW, Kim K, Taylor S, Romano PS, Panacek EA, Goodell PB, Solnick JV, Cohen SH. Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era. JAMA Intern Med. 2015 Nov;175(11):1792-801. doi: 10.1001/jamainternmed.2015.4114.
Results Reference
result

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Vancomycin for C Difficile NAAT+/EIA- Hematology Oncology Patients

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