Clostridium Difficile Infection, Hematologic Diseases, Bone Marrow Transplant, Oncologic Disorders
Conditions
Keywords
microbiome, bone marrow transplantation, Clostridium difficile, metabolomics, vancomycin
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.
Interventions
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.
DRUGPlacebo Oral Capsule
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.
Sponsors
Medical College of Wisconsin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
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.
Intervention model description
Patients will be divided into two groups, one receiving oral vancomycin capsules, the other receiving oral placebo capsules.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Clostridium Difficile Bacterial Loads in the Stool | First sample versus last stool sample collected, up to 90 days | Changes in Clostridium difficile bacterial counts from stool as determined by quantitative polymerase chain reaction (PCR). Values obtained from initial sample (pre-treatment) were compared with values from the last sample obtained for each patient. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSilvia Munoz-Price, M.D., Ph.D.
Medical College of Wisconsin
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 5 / 5 | 4 / 4 |
| serious Total, serious adverse events | 2 / 5 | 1 / 4 |
Outcome results
None listed