Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Infection

Pseudomembranous Colitis Clinical Trial

Official title:

Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Colitis in Patients Who Have Failed Conventional Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00304356
• Other study ID #: H-15601
• Status: Completed
• Phase: Phase 3
• First received: March 16, 2006
• Last updated: May 8, 2017
• Start date: January 2004
• Est. completion date: January 2007

Study information

• Verified date: May 2017
• Source: VA Medical Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Clostridium Enterocolitis
• Colitis
• Enterocolitis
• Enterocolitis, Pseudomembranous
• Pseudomembranous Colitis

Intervention

Drug:
• Nitazoxanide
500 mg bid

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	Michael E. Debakey VA Medical Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Daniel M. Musher MD	Baylor College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nitazoxanide	stopping of diarrhea	30 days