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

Hematologic Diseases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03030248
• Other study ID #: PRO00028749
• Status: Completed
• Phase: Phase 2
• Start date: June 1, 2018
• Est. completion date: June 30, 2020

Study information

• Verified date: July 2020
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Marrow Transplant
• Clostridium Difficile Infection
• Clostridium Infections
• Hematologic Diseases
• Oncologic Disorders

Intervention

Drug:
• Vancomycin Oral Capsule
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.
• Placebo 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.

Locations

Country	Name	City	State
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

References & Publications (8)

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 — View Citation

Isaac S, Scher JU, Djukovic A, Jiménez 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. Epub 2016 Oct 5. — View 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. — View 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. Review. — View 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 I — View 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. — View 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). pii: e00045-15. doi: 10.1128/mSphere.00045-15. eCollection 2016 Jan-Feb. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Pre-treatment, 1, 7, 14, 21, 28, and 90 days past the beginning of treatment