Clostridium Enterocolitis, Pseudomembranous Colitis
Conditions
Keywords
Clostridium difficile Associated Diarrhea
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.
Interventions
DRUGNitazoxanide
500 mg bid
Sponsors
Baylor College of Medicine
Daniel M. Musher MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nitazoxanide | 30 days | stopping of diarrhea |
Countries
United States
Participant flow
Recruitment details
Chart review at the Houston VA for patients treated with Nitazoxanide who have failed previous therapy.
Pre-assignment details
This is a retrospective chart review.
Participants by arm
| Arm | Count |
|---|---|
| Nitazoxanide Patients with C. difficle who exhibit diarrhea and received nitazoxanide. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Nitazoxanide | number is 0 | 1 |
| Nitazoxanide | Physician Decision | 5 |
Baseline characteristics
| Characteristic | Nitazoxanide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Age, Continuous | 27 years STANDARD_DEVIATION 27 |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
Nitazoxanide
stopping of diarrhea
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nitazoxanide | Nitazoxanide | 27 participants |