Clinical trial NCT00384527: Study of Nitazoxanide in the Treatment of Clostridium Difficile-associated Disease
Official title: Multicenter, Double-blind Study of Nitazoxanide Compared to Vancomycin in the Treatment of Clostridium Difficile-associated Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Clostridium Infections
Keywords: Clostridium difficile
Lead sponsor: Romark Laboratories L.C.
Sponsor class: INDUSTRY
First posted: 2006-10-06
Enrollment: 50
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 of the study is to demonstrate non-inferiority of nitazoxanide compared to vancomycin in resolving symptoms of Clostridium difficile-associated disease (CDAD).


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical response (resolution of all symptoms of CDAD)
timeFrame: End of treatment (day 12-14 after beginning treatment)
Secondary outcomes:
measure: Time from first dose to resolution of symptoms of CDAD
timeFrame: Any time after beginning treatment and must be sustained through end of treatment visit
measure: Microbiological Recurrence
timeFrame: Clinical response at end of treatment visit with recurrence of symtpoms prior to study day 31 and C. difficile toxins detected in stool.
measure: Sustained clinical response
timeFrame: End of treatment response sustained through study day 31.
measure: Clinical Recurrence
timeFrame: Clinical response at the end of treatment with recurrent symptoms of CDAD prior to study day 31, but no C. difficile toxins detected.
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Torrance Memorial Hospital
state: California
city: Bay Pines
country: United States
facility: Bay Pines VAMC
state: Florida
city: Atlanta
country: United States
facility: Atlanta Institute for Medical Research
state: Georgia
city: Atlanta
country: United States
facility: Wellstar Clinical Trials
state: Georgia
city: Indianapolis
country: United States
facility: Richard L. Roudebush VAMC
state: Indiana
city: New Orleans
country: United States
facility: Oschner Clinic Foundation
state: Louisiana
city: Ann Arbor
country: United States
facility: John D. Dingell VAMC
state: Michigan
city: Troy
country: United States
facility: Center for Digestive Health
state: Michigan
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Houston
country: United States
facility: Michael E. Debakey VAMC
state: Texas
Study officials:
affiliation: John D. Dingell VAMC
name: Carol Kauffman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Atlanta Institute for Medical Research
name: Adam Bressler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wellstar Clinical Trials
name: Wesley Bray, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Winthrop University Hospital
name: James Grendell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Richard L. Roudebush VA Medical Center
name: Bradley Allen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Digestive Health
name: Partha Nandi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Michael E. Debakey VAMC
name: Daniel Musher, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oschner Clinic Foundation
name: Julia Garcia-Diaz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Torrence Memorial Hospital
name: David Rand, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bay Pines VAMC
name: David Johnson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Musher DM, Logan N, Bressler AM, Johnson DP, Rossignol JF. Nitazoxanide versus vancomycin in Clostridium difficile infection: a randomized, double-blind study. Clin Infect Dis. 2009 Feb 15;48(4):e41-6. doi: 10.1086/596552.