Official Title: “Multicenter, Double Blind, Metronidazole Controlled, Dose Range Finding Study of Nitazoxanide in the Treatment of Clostridium Difficile Colitis”

The primary objective is to demonstrate non-inferiority of nitazoxanide administered 500 mg b.i.d compared to metronidazole administered 250 mg q.i.d. in resolving symptoms of Clotridium difficile colitis after seven days of treatment. Secondary objectives are to provide information on the times from first dose to last unformed stool and resolution of symptoms of colitis, the sustained response rates for the different tratment groups and the effect of treatment on Clostridium difficile toxin enzyme immunoassay/culture results during hospitalization.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study

Intervention(s) in this Clinical Trial

• Drug: Nitazoxanide
• Drug: Metronidazole

Primary Measures

• Clinical response (resolution of all symptoms present at baseline) recorded on day 8

Secondary Measures

• Time from first dose to passage of last unformed stool
• Time from first dose to resolution of symptoms
• Sustained clinical response (resolution of all symptoms present at baseline with no recurrence during follow-up)
• C. difficile toxin enzyme immunoassay/culture results during hospitalization

Inclusion Criteria:

• Age ≥ 18 years.
• In-patients with new onset of colitis evidenced by diarrhea (≥3 unformed stools within 24 hours), with one or more of the following: abdominal pain or cramps; peripheral leukocytosis, otherwise unexplained; or fever, otherwise unexplained.
• C. difficile toxin A or B detected in a stool specimen obtained within 7 days before enrollment by enzyme immunoassay.
• Patients able to take oral medications.
• Patients willing to avoid the following medications during the study: oral and intravenous metronidazole, oral vancomycin, anti-peristaltic drugs, opiates, Saccharomyces cerevisiae (baker’s yeast), Lactobacillus GC, cholestyramine or colestipol. [Patients on opiates may be included in the study as long as they were taking opiates prior to enrollment and the dose is not increased during the study].
• Patients willing to abstain from alcohol during the 10-day treatment duration and for two days following treatment.

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).
• 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 2 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. A double barrier method, oral birth control pills administered for at least 2 monthly cycles prior to study drug administration, an IUD, or medroxyprogesterone acetate administered intramuscularly for a minimum of one month prior to study drug administration are acceptable methods of birth control for inclusion into the study. In addition, female patients of child-bearing potential should have a baseline pregnancy test and should agree to continue an acceptable method of birth control for the duration of the study (including follow-up).
• Patients taking phenytoin, celecoxib, and/or losartan. [Patients taking Coumadin® (warfarin) may be included as long the prothrombin time is monitored at least twice weekly during the first 2 weeks of the study and at least weekly thereafter].
• Patients with severe renal or hepatic impairment.
• Patients who are clinically unstable (e.g., patients with signs of toxic megacolon or imminent perforation).
• Serious systemic disorders incompatible with the study.
• History of hypersensitivity to metronidazole.

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

Ian M Baird, M.D. Principal Investigator Remington-Davis Inc., and Riverside Infection Consultants, Inc.  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00417872

Study ID Number: RM01-2015

ClinicalTrials.gov Identifier: NCT00417872

Health Authority: United States: Food and Drug Administration