Study of Nitazoxanide in the Treatment of Clostridium Difficile-associated Disease

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate non-inferiority of nitazoxanide compared to vancomycin in resolving symptoms of Clostridium difficile-associated disease (CDAD).

Official Title
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Multicenter, Double-blind Study of Nitazoxanide Compared to Vancomycin in the Treatment of Clostridium Difficile-associated Disease

Conditions
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Clostridium Infections

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Patients with new onset of disease evidenced by diarrhea (≥ 3 unformed stools within 24 hours), and one or more of the following symptoms of CDAD: abdominal pain or cramps peripheral leukocytosis fever C. difficile toxin A or B detected in a stool specimen obtained within 3 days before enrollment by enzyme immunoassay. Patients willing to avoid the following medications during the study: oral and intravenous metronidazole oral vancomycin anti-peristaltic drugs opiates (patients on opiates may be included in the study if they were taking opiates prior to enrollment and the dose is not increased during the study) Saccharomyces cerevisiae (baker's yeast) Lactobacillus GG cholestyramine colestipol Exclusion Criteria: Patients with other known causes of diarrhea or colitis (e.g., Shigella, Salmonella, Cryptosporidium parvum, Giardia lamblia, Entamoeba histolytica, inflammatory bowel disease, irritable bowel syndrome, advanced AIDS or chemotherapy for malignancy). Patients that commonly have 3 or more stools per day and/or severe abdominal pain in the absence of CDAD. Patients with severe lactose intolerance. Patients with more than 1 recurrence of CDAD during the 6 months prior to enrollment. Patients unable to take oral medications. Use within 1 week of enrollment of any drug or therapy with anti-C. difficile activity such as oral or intravenous metronidazole and oral vancomycin. [Patients that have taken up to 3 doses of metronidazole or vancomycin can be included in the study]. Females of child bearing age who are either pregnant, breast-feeding or not using birth control and are sexually active. Patients who are either clinically unstable (e.g., fulminant disease patients with signs of toxic megacolon, imminent perforation, colectomy or death) or unlikely to live throughout the 31-day duration of the study due to underlying illness. History of hypersensitivity to nitazoxanide or vancomycin or any active ingredient in the formulations.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Nitazoxanide<br>* One nitazoxanide 500 mg tablet twice daily plus one vancomycin-placebo capsule four times daily for 10 days.<br>* Other names: Alinia;|
| Active Comparator: 2<br> | Drug: Vancomycin<br>* One vancomycin 125 mg capsule four times daily plus one nitazoxanide-placebo twice daily for 10 days.<br>* Other names: VANCOCIN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response (resolution of all symptoms of CDAD) |  | End of treatment (day 12-14 after beginning treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from first dose to resolution of symptoms of CDAD |  | Any time after beginning treatment and must be sustained through end of treatment visit | 
| Microbiological Recurrence |  | Clinical response at end of treatment visit with recurrence of symtpoms prior to study day 31 and C. difficile toxins detected in stool. | 
| Sustained clinical response |  | End of treatment response sustained through study day 31. | 
| Clinical Recurrence |  | Clinical response at the end of treatment with recurrent symptoms of CDAD prior to study day 31, but no C. difficile toxins detected. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clostridium difficile