Official Title: “Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Colitis in Patients Who Have Failed Conventional Therapy”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: Nitazoxanide

Primary Measures

• Resolution of diarrhea

Secondary Measures

• Time to resolution of diarrhea
• Recurrence rate
• Number of stools
• Treatment success

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

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: VA Medical Center, Houston

Overall Clinical Trial Officials and Contacts

Daniel M Musher, M.D. Principal Investigator Baylor College of Medicine, Houston VA Medical Center  

Overall Contact: Nancy Logan, M.A. 713-791-1414 njarrar@bcm.tmc.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00304356

Study ID Number: H-15601

ClinicalTrials.gov Identifier: NCT00304356

Health Authority: United States: Institutional Review Board