Clinical trial NCT00417872: Study of Nitazoxanide in the Treatment of Clostridium Difficile Colitis
Official title: Multicenter, Double Blind, Metronidazole Controlled, Dose Range Finding Study of Nitazoxanide in the Treatment of Clostridium Difficile Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clostridium Difficile
Keywords: Clostridium difficile
Lead sponsor: Romark Laboratories L.C.
Sponsor class: INDUSTRY
First posted: 2007-01-04
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Clinical response (resolution of all symptoms present at baseline) recorded on day 8
Secondary outcomes:
measure: Time from first dose to passage of last unformed stool
measure: Time from first dose to resolution of symptoms
measure: Sustained clinical response (resolution of all symptoms present at baseline with no recurrence during follow-up)
measure: C. difficile toxin enzyme immunoassay/culture results during hospitalization
Other outcomes:
Locations:
city: St. Petersburg
country: United States
facility: Bayfront Medical Center and Edward White Hospital
state: Florida
city: Marietta
country: United States
facility: WellStar Infectious Diseases
state: Georgia
city: Columbus
country: United States
facility: Remington-Davis, Inc., and Riverside Infection Consultants, Inc.
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: The Reading Hospital and Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Houston Veterans Affairs Hospital
state: Texas
city: Houston
country: United States
facility: St. Luke's Episcopal Hospital
state: Texas
Study officials:
affiliation: Remington-Davis Inc., and Riverside Infection Consultants, Inc.
name: Ian M Baird, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: CHI St. Luke's Health, Texas
name: Herbert L DuPont, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Lehigh Valley Hospital
name: Arvind K Gupta, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Reading Hospital and Medical Center
name: Robert S Jones, D.O.
role: PRINCIPAL_INVESTIGATOR
affiliation: WellStar Infectious Diseases, Summit Surgical Specialists, and WellStar Kennestone Hospital
name: Arnold L Lentnek, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Houston Veterans Affairs Hospital
name: Daniel Musher, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Bayfront Medical Center and Edward White Hospital
name: Fadi Saba, M.D.
role: PRINCIPAL_INVESTIGATOR
References: