Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Infection

• ClinicalTrials.gov Identifier: NCT00304356
• Recruitment Status: Completed
• First Posted: March 17, 2006
• Results First Posted: December 15, 2017
• Last Update Posted: December 15, 2017
• Sponsor: Daniel M. Musher MD
• Collaborator: Baylor College of Medicine
• Information provided by (Responsible Party): Daniel M. Musher MD, VA Medical Center, Houston

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Clostridium Enterocolitis; Pseudomembranous Colitis	Drug: Nitazoxanide	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Colitis in Patients Who Have Failed Conventional Therapy
• Study Start Date: January 2004
• Actual Primary Completion Date: January 2007
• Actual Study Completion Date: January 2007

Arms and Interventions

Arm	Intervention/treatment
active drug; 500 mg nitazoxanide bid given to patient	Drug: Nitazoxanide; 500 mg bid; Other Name: alinia

Outcome Measures

Primary Outcome Measures :

1. Nitazoxanide [ Time Frame: 30 days ]
   stopping of diarrhea

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Michael E. Debakey VA Medical Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Daniel M. Musher MD

Baylor College of Medicine

Investigators

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

More Information

• Responsible Party: Daniel M. Musher MD, PI, VA Medical Center, Houston
• ClinicalTrials.gov Identifier: NCT00304356 History of Changes
• Other Study ID Numbers: H-15601
• First Posted: March 17, 2006
• Results First Posted: December 15, 2017
• Last Update Posted: December 15, 2017
• Last Verified: May 2017

Keywords provided by Daniel M. Musher MD, VA Medical Center, Houston:

Clostridium difficile Associated Diarrhea

Additional relevant MeSH terms:

Enterocolitis, Pseudomembranous; Colitis; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Nitazoxanide; Antiparasitic Agents; Anti-Infective Agents