Clinical trial NCT00304356: Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Infection
Official title: Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Colitis in Patients Who Have Failed Conventional Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridium Enterocolitis
Pseudomembranous Colitis
Keywords: Clostridium difficile Associated Diarrhea
Lead sponsor: Michael E. DeBakey VA Medical Center
Sponsor class: FED
Collaborators: name: Baylor College of Medicine
First posted: 2006-03-17
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is for compassionate use of nitazoxanide in the treatment of diarrheal disease due to Clostridium difficile infection when the patient has failed previous treatment with metronidazole or vancomycin.

Detailed description: Clostridium difficile is the leading cause of nosocomial diarrheal disease associated with antibiotic therapy. This is a debilitating condition with substantial morbidity and a mortality that may be around 2-3%. There has been an enormous increase in this disease at the VA Medical Center during the past two years, just as has occurred at other hospitals throughout the United States.

Currently recommended therapy for this condition is metronidazole, given orally. About 15-20% of patients fail to respond to initial therapy with metronidazole, and another 20% relapse after treatment. Relapses may be treated with another course of metronidazole; about one-half will respond to this therapy. The failures are treated with oral vancomycin, but this drug also has a failure rate of 10-20%. There is, at present, no other accepted therapy (although some articles in the literature favor vancomycin with ingested bacteria from benign species). Furthermore, there is a strong risk to the emergence of resistant bacteria when hospitalized patients are treated with oral vancomycin.

Nitazoxanide is an FDA approved drug that is marketed in the U.S. and has been widely used throughout the world to treat parasitic diseases of the gastrointestinal tract; several million children have been treated with this drug during the past decade. Nitazoxanide has been approved as an antiprotozoal agent for oral administration in pediatric patients, ages 1 through 11, with diarrhea. The drug acts by interfering with anaerobic metabolic pathways, and it has been shown to have excellent in vitro activity against C. difficile. We hypothesized that this drug was both safe and effective as an alternative in patients who have diarrheal disease caused by C. difficile. The IRB approved a double-blind protocol to compare metronidazole with nitazoxanide, and we have treated a total of 16 patients so far under this protocol.

In our IRB-approved double blind study (by design, two thirds of the subjects have been randomized to the nitazoxanide), our patients have appeared to have a good response rate -- so good, in fact, that we think that nitazoxanide may be a better drug to treat this infection than either metronidazole or vancomycin.

Eligibility criteria: Inclusion Criteria:

* Patient must be \> 18 years of age
* Clinical diagnosis of C. difficile associated disease, based on the new onset of diarrhea, abdominal discomfort, or otherwise unexplained fever or leukocytosis
* Diagnosis of C. difficile colitis proven by positive assay for C. difficile toxin in feces
* Disease has been treated, and the symptoms failed to respond to treatment with metronidazole or vancomycin, or symptoms promptly relapsed after completing a course of therapy with either of these drugs
* Able to take oral medication

Exclusion Criteria:

* Patients with other recognized causes of diarrhea or colitis
* Women of child bearing age who are pregnant, breast feeding, or not using birth control
* Patients taking coumadin, phenytoin, celecoxib, or losartan
* Patients with renal insufficiency (BUN or creatinine \>2 times baseline)
* Serious systemic disorder incompatible with the study

Primary outcomes:
measure: Nitazoxanide
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Michael E. Debakey VA Medical Center
state: Texas
Study officials:
affiliation: Baylor College of Medicine, Houston VA Medical Center
name: Daniel M Musher, M.D.
role: PRINCIPAL_INVESTIGATOR
References: