Official Title: “Study of the Efficacy of Loperamide in Treating Patients for Clostridium Difficile Colitis and Diarrheal Disease of Unknown Cause Associated With Prior Antibiotic Therapy.”

To determine whether symptomatic treatment of the diarrhea in CDAD reduces morbidity and mortality of this serious nosocomial infection in patients who have antibiotic-associated diarrhea. Both C. diff positive and negative patients will be included.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

Colitis due to Clostridium difficile has been increasingly recognized as a serious nosocomial problem. Recommended therapy is with metronidazole, 500 mg four times daily for 10 days.

About 80% of patients respond to this therapy. However, the response may be be delayed, in which case debilitation due to diarrhea progresses. The 20% who do not respond tend to be sicker to start, and debilitation due to diarrhea is a severe problem. In reviewing the medical literature, we discovered that the earliest papers on C. difficile colitis emphasized symptomatic therapy with 'lomotil' (diphenoxylate with atropine).

Treatment to suppress the diarrhea fell out of favor in the late 1970's because of the theoretical consideration that it was better to expel than to retain the bacterial toxins.

However, the patients who are affected by C. difficile colitis are increasingly elderly and debilitated, and suffer substantial morbidity from the diarrhea. We have shown that the 90-day associated mortality is >20%.

Loperamide is a standard treatment for diarrhea, and is available over the counter under the name, Imodium. Based on a few anecdotal reports, this drug is regarded as contraindicated in patients whose diarrheal disease is bacterial. But it is used widely, and generally without any diagnosis being established. We now propose to administer loperamide or placebo to patients with CDAD in order to determine whether the antidiarrheal drug reduces morbidity associated with the infection. We will monitor our patients closely both to observe potential benefits and/or adverse events.

In the addendum, we propose to include patients who have antibiotic-associated diarrheal disease that is not due to C. difficile. There are many patients who have antibiotic-associated diarrheal disease who test negative for C. difficile. We believe that these patient may benefit from loperamide treatment as well.

Intervention(s) in this Clinical Trial

• Drug: loperamide
  • 4 mg PO initially and 2 mg after each water stoll not to exceed 10 mg qd
• Drug: placebo
  • 4 mg PO initially and 2 mg after each water stoll not to exceed 10 mg qd

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • Loperamide
• Placebo Comparator: B
  • Placebo

Primary Measures

• To determin symptomatic treatment of diarrhea with loperamide in antibiotic associated diarrhea
  • Time Frame: 2 years
    Safety Issue?: Yes

Secondary Measures

• To measure the safety and efficacy of loperamide in the control of antibiotic associated diarrhea in hospitalized patients
  • Time Frame: 2 years
    Safety Issue?: Yes

Inclusion Criteria:

• Patients with diarrheal stools considered to be antibiotic associated

Exclusion Criteria:

• Inability of sign consent
• Patient with other known gastrointestinal disease
• Patients receiving tube feeding or fecal incontinence prior to receiving antibiotics

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: VA Medical Center, Houston

Overall Clinical Trial Officials and Contacts

Daniel M Musher, MD Principal Investigator VA Medical Center, Houston  

Overall Contact: Nancy D Logan, MA 504-988-7889 njarrar@bcm.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00591357

Study ID Number: H-21387

ClinicalTrials.gov Identifier: NCT00591357

Health Authority: United States: Institutional Review Board