Blood and Lymph Conditions

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Bacterial Infections and Mycoses

Twelve patients found to be colonized with C. difficile will undergo twice a day potato starch supplementation.

Potato starch will be given twice a day for up to 14 days, discharge, or death, whichever occurs first.

Potato starch

Clostridium difficile causes \~453,000 infections and \~29,300 deaths per year in the US, making it the most common hospital acquired infection in the country. C. difficile is an anaerobic bacterium that has the capacity to inhabit the colon of humans and other mammals. Initially thought to be a commensal, it was later found to be associated with antibiotic induced enterocolitis. Since then, it has gradually become one of the most important healthcare associated pathogens. C. difficile infection (CDI) causes colitis, which is inflammation of the colonic mucosa with a spectrum of severity from mild to more protracted diarrhea, abdominal pain, fever, toxic megacolon, sepsis, and in some instances death. Mortality occurs despite the existence of three antibiotic options. CDI is also associated with higher hospital readmission rates, and associated healthcare costs in the US are estimated at 4.8 billion dollars annually. Due to the significance of C. difficile in healthcare, hospital level C. difficile rates are publically reported and closely scrutinized by the Centers for Medicare and Medicaid. Standard infection control bundles are proving to be insufficient for controlling the national C. difficile problem. Better understanding of the biological steps preceding clinical infection and reversal of the underlying gut dysbiosis will allow us to curtail our C. difficile epidemic. The present study aims to manipulate the gut microbiota to halt the biological progression of C. difficile.

CDI is a serious problem in hematology-oncology patients. The incidence of CDI in the hematology-oncology population is much higher than in other populations and hematology-oncology inpatient units frequently have the highest incidence of CDI cases within an institution. Additionally, hematology-oncology patients have high rates of C. difficile colonization upon hospitalization and more than 50% of patients detected with C. difficile colonization before bone marrow transplantation end up diagnosed with hospital associated CDI. This finding is not trivial as CDI treatment with oral vancomycin causes major and prolonged perturbations of their intestinal microbiota, which has been associated with higher mortality. In addition to the usual complications of CDI, a higher incidence of graft-versus-host-disease has been described in patients with CDI.

Aim 1/Objective 1. Establish the feasibility of oligosaccharide supplementation and twice a week stool collections among 12 C. difficile colonized hematology-oncology inpatients. It will be determined if at least 70% of the oligosaccharide dosages are taken by at least 8 (\>=66%) of the 12 enrolled patients. Additionally, the ability to collect at least 50% of the scheduled stool samples will be evaluated.

Aim 1 will provide important information about the ideal food/drink to mix the potato starch supplemented in this study. The knowledge gained in this pilot will be used to design a future phase II or III clinical trial.

Aim 2. Explore the impact of oligosaccharide supplementation on C. difficile loads and relative abundance of Firmicutes. All stool samples will undergo 16S ribosomal ribonucleic acid (rRNA) and bioinformatics at the MCW's Genomic and Precision Medicine Center and C. difficile quantitative polymerase chain reaction (qPCR) at the PI's research laboratory. Historical controls will be obtained from a group of over 450 hematology-oncology inpatients who underwent at least one C. difficile surveillance test and whose stool samples are currently being processed for 16S rRNA by the PI's team. Controls at a 3:1 ratio with cases will be matched based on underlying disease, unit of admission, antibiotic use, baseline C. difficile fecal loads, and baseline relative abundance of Firmicutes.

Objective 2a. Evaluate the impact of oligosaccharide supplementation on the change of C. difficile fecal loads when compared to historical controls.

Objective 2b. Explore the effect of oligosaccharide supplementation on the change in relative abundance of Firmicutes when compared to historical controls.

It is expected a reduction will occur in C. difficile fecal loads during oligosaccharide supplementation when compared to matched controls. Conversely, it is expected an increase in the relative abundance of Firmicutes (or some of its operational taxonomic units; OTUs) during oligosaccharide replacement will occur when compared to matched controls. The knowledge gained with Objectives 2a and 2b will be used to determine the sample size needed to design future phase II or phase III clinical trials.

Oligosaccharide for Cdiff(+) Heme-onc Patients

Oligosaccharide Supplementation Among Hematology-Oncology Clostridium Difficile Colonized Patients

Samples will be collected twice a week (4-5 times during supplementation) and one time at day 21 or discharge, whichever happens first.

Patients will be provided with a diary in which they will document compliance with oligosaccharide intake. It is anticipated ≥70% of intended doses to be fully administered by the patient.

It is expected ≥50% of stool samples to be correctly collected and processed.

Stool samples collected for diagnosis and any additional stool collections will be thawed in batches and one cc aliquot will be extracted refreezing the remaining sample at -80 degrees F. One cc aliquot will then be divided into 4 sub-samples of equal volume and with the same unique identifier. This identifier will be able to chronologically cluster samples by each unique patient. A sample will be used for C. difficile qPCR quantitative determination.

Sub-sample of stool from diagnosis, and additional stool collections will be used for 16S ribosomal ribonucleic acid gene sequencing to determine the microbiome community structure

Medical College of Wisconsin

Professor

Pharmaceutical Solutions

All Drugs and Chemicals

Micronutrients

Anti-Infective Agents

Dermatologic Agents

Iron

Vancomycin

Titanium dioxide

Anti-Bacterial Agents

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.

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.

Vancomycin 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.

Placebo Oral Capsule

Silvia Munoz-Price, M.D., Ph.D.

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.

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.

Patients will be divided into two groups, one receiving oral vancomycin capsules, the other receiving oral placebo capsules.

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.

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

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

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.

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

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Urinary Tract Infections

Urogenital Diseases

Male Urogenital Diseases

Urologic Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

Ciprofloxacin

Antibiotics, Antitubercular

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Jean V Joseph, M.D.

The aim of this study is to determine whether antibiotics prophylaxis at the time of urinary catheter removal decreases the number of symptomatic urinary tract infections in patients after radical prostatectomy. In addition, the investigators aim to determine whether antibiotic prophylaxis is potentially harmful to patients (e.g. adverse reactions from antibiotic use, resistant bacteria in the urine, Clostridium difficile infections etc.). The investigators also aim to identify specific populations that may be at higher risk of developing urinary tract infections with urinary catheter use after radical prostatectomy.

Antibiotic Prophylaxis for Urinary Catheter Removal After Radical Prostatectomy

After removal of the catheter, urine was tested for infection whenever symptoms were experienced by the participants from the time they enrolled to 12 months following their operation.

Development of Clostridium difficile was measured in stool for clostridium difficile infection by enzyme immunoassay (EIA) and/or polymerase chain reaction (PCR).

Bacterial cultures were performed on urine and the presence of the following bacteria was determined: Acinetobacter, Coagulase-negative staphylococci, Diptherioids, Escherichia coli, Enterobacter, Enterococcus, Klebsiella pneumonia, and Lactoferrin. Participants who were positive for one or more of these were considered positive.

University of Rochester

Professor of Urology and Oncology

Adverse events were only collected on patients who had their catheter removed (ie. started period 2).

No Antibiotic

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Baseline characteristics were only collected on patients who had their catheter removed (ie. started period 2).

Jean Joseph

this outcome measure was only collected on patients who had their catheter removed (ie. started period 2)

Number of Participants With a Positive Urinary Tract Infection

Number of Participants Positive for Clostridium Difficile

10 participants in the Ciprofloxacin arm and 16 participants in the no antibiotic arm did not have samples collected for testing.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Oligosaccharide for Cdiff(+) Heme-onc Patients	NCT03778606	Clostridium Dif... Hematologic Dis...	Potato starch	18 Years -	Medical College of Wisconsin
Oligosaccharide for Cdiff(+) Heme-onc Patients	NCT03778606	Clostridium Dif... Hematologic Dis...	Potato starch	18 Years -	Medical College of Wisconsin
Vancomycin for C Difficile NAAT+/EIA- Hematology Oncology Patients	NCT03030248	Clostridium Dif... Hematologic Dis... Bone Marrow Tra... Oncologic Disor...	Vancomycin Oral... Placebo Oral Ca...	18 Years -	Medical College of Wisconsin
Antibiotic Prophylaxis for Urinary Catheter Removal After Radical Prostatectomy	NCT02247960	Prostate Cancer Urinary Tract I... Clostridium Dif...	Ciprofloxacin	18 Years -	University of Rochester

Spots Global Cancer Trial Database for clostridium difficile