Compassionate Use of Nitazoxanide for the Treatment of Clostridium Difficile Infection

• Sponsor: Daniel M. Musher MD (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00304356
• Collaborator: Baylor College of Medicine (Other)
• Enrollment: 22
• Locations: 2
• Arm: 1
• Duration (Months): 36
• Patients Per Site: 11
• Patients Per Site Per Month: 0.3

Study Details

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
• Actual Enrollment: 22 participants
• Allocation: N/A
• 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: Jan 1, 2004
• Actual Primary Completion Date: Jan 1, 2007
• Actual Study Completion Date: Jan 1, 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Nitazoxanide [30 days]

   stopping of diarrhea

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor College of Medicine	Houston	Texas	United States	77030
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daniel M. Musher MD, PI, Michael E. DeBakey VA Medical Center
• ClinicalTrials.gov Identifier: NCT00304356
• Other Study ID Numbers: H-15601
• First Posted: Mar 17, 2006
• Last Update Posted: Dec 15, 2017
• Last Verified: May 1, 2017

• Keywords provided by Daniel M. Musher MD, PI, Michael E. DeBakey VA Medical Center: Clostridium difficile Associated Diarrhea
• Additional relevant MeSH terms: Enterocolitis, Pseudomembranous; Colitis; Enterocolitis; Nitazoxanide

Study Results

Participant Flow

Recruitment Details	Chart review at the Houston VA for patients treated with Nitazoxanide who have failed previous therapy.
Pre-assignment Detail	This is a retrospective chart review.

Arm/Group Title	Nitazoxanide
Arm/Group Description
Period Title: Nitazoxanide
STARTED	27
COMPLETED	22
NOT COMPLETED	5
Period Title: Nitazoxanide
STARTED	27
COMPLETED	22
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Nitazoxanide
Arm/Group Description	Patients with C. difficle who exhibit diarrhea and received nitazoxanide.
Overall Participants	27
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	27 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27 (27)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	27 100%
Region of Enrollment (participants) [Number]
United States	27 100%

Outcome Measures

1. Primary Outcome

Title	Nitazoxanide
Description	stopping of diarrhea
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nitazoxanide
Arm/Group Description	time diarrhea from C. difficile stopped.
Measure Participants	27
Number [participants]	27 100%

Adverse Events

Time Frame	30 days
Arm/Group Title	Nitazoxanide
Arm/Group Description
All Cause Mortality
	Nitazoxanide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nitazoxanide
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Other (Not Including Serious) Adverse Events
	Nitazoxanide
	Affected / at Risk (%)	# Events
Total	0/27 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.