Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Infection

NCT ID: NCT00304356

Last Updated: 2017-12-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2007-01-31

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.

Conditions

Clostridium Enterocolitis; Pseudomembranous Colitis

Keywords

Clostridium difficile Associated Diarrhea

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

active drug

500 mg nitazoxanide bid given to patient

Group Type: OTHER

Nitazoxanide

Intervention Type: DRUG

500 mg bid

Interventions

Nitazoxanide

500 mg bid

Intervention Type: DRUG

Other Intervention Names

alinia

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

Daniel M. Musher MD

FED

Sponsor Role: lead

Responsible Party

Daniel M. Musher MD

PI

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daniel M Musher, M.D.

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine, Houston VA Medical Center

Locations

Baylor College of Medicine

Houston, Texas, United States

Michael E. Debakey VA Medical Center

Houston, Texas, United States

Countries

United States

Other Identifiers

H-15601

Identifier Type: -

Identifier Source: org_study_id