Official Title: “Multicenter, Double-Blind Study of Nitazoxanide Compared to Vancomycin in the Treatment of Clostridium Difficile-Associated Disease”

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).

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2007

Intervention(s) in this Clinical Trial

• Drug: Nitazoxanide
  • One nitazoxanide 500 mg tablet twice daily plus one vancomycin-placebo capsule four times daily for 10 days.
• Drug: Vancomycin
  • One vancomycin 125 mg capsule four times daily plus one nitazoxanide-placebo twice daily for 10 days.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Active Comparator: 2

Primary Measures

• Clinical response (resolution of all symptoms of CDAD)
  • Time Frame: End of treatment (day 12-14 after beginning treatment)
    Safety Issue?: No

Secondary Measures

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

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Romark Laboratories L.C.

Overall Clinical Trial Officials and Contacts

Carol Kauffman, MD Principal Investigator John D. Dingell VAMC  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00384527

Study ID Number: RM01-3032

ClinicalTrials.gov Identifier: NCT00384527

Health Authority: United States: Food and Drug Administration