Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Infection

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 Overview

• Status: Completed
• Conditions: Clostridium Enterocolitis; Pseudomembranous Colitis
• Intervention / Treatment: Drug: Nitazoxanide

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: active drug; 500 mg nitazoxanide bid given to patient	Drug: Nitazoxanide; 500 mg bid; Other Names: alinia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitazoxanide	stopping of diarrhea	30 days

Collaborators and Investigators

• Sponsor: Daniel M. Musher MD
• Collaborators: Baylor College of Medicine
• Investigators: Principal Investigator: Daniel M Musher, M.D., Baylor College of Medicine, Houston VA Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: March 16, 2006
• First Submitted That Met QC Criteria: March 16, 2006
• First Posted (Estimate): March 17, 2006

Study Record Updates

• Last Update Posted (Actual): December 15, 2017
• Last Update Submitted That Met QC Criteria: May 8, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Clostridium difficile Associated Diarrhea
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections; Enterocolitis; Colitis; Enterocolitis, Pseudomembranous; Anti-Infective Agents; Antiparasitic Agents; Nitazoxanide
• Other Study ID Numbers: H-15601