Study of Nitazoxanide in the Treatment of Clostridium Difficile Colitis

Condition(s) targeted: Clostridium Difficile

Intervention: Nitazoxanide (Drug); Metronidazole (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Romark Laboratories L.C.

Official(s) and/or principal investigator(s):
Ian M Baird, M.D., Principal Investigator, Affiliation: Remington-Davis Inc., and Riverside Infection Consultants, Inc.
Herbert L DuPont, M.D., Principal Investigator, Affiliation: St. Luke's Episcopal Hospital, Texas
Arvind K Gupta, M.D., Principal Investigator, Affiliation: Lehigh Valley Hospital
Robert S Jones, D.O., Principal Investigator, Affiliation: The Reading Hospital and Medical Center
Arnold L Lentnek, M.D., Principal Investigator, Affiliation: WellStar Infectious Diseases, Summit Surgical Specialists, and WellStar Kennestone Hospital
Daniel Musher, M.D., Principal Investigator, Affiliation: Houston Veterans Affairs Hospital
Fadi Saba, M.D., Principal Investigator, Affiliation: Bayfront Medical Center and Edward White Hospital

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.

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

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

Primary outcome: Clinical response (resolution of all symptoms present at baseline) recorded on day 8

Secondary outcome:

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Bayfront Medical Center and Edward White Hospital, St. Petersburg, Florida 33713, United States

WellStar Infectious Diseases, Marietta, Georgia 30060, United States

Remington-Davis, Inc., and Riverside Infection Consultants, Inc., Columbus, Ohio 43214, United States

Lehigh Valley Hospital, Allentown, Pennsylvania 18103, United States

The Reading Hospital and Medical Center, West Reading, Pennsylvania 19611, United States

St. Luke's Episcopal Hospital, Houston, Texas 77030, United States

Houston Veterans Affairs Hospital, Houston, Texas 77030, United States

Starting date: January 2004
Ending date: September 2005
Last updated: January 3, 2007