Efficacy of Loperamide for C. Difficile Colitis and Other Diarrheal Diseases Associated With Antibiotic Therapy (loperamide)

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 Overview

• Status: Suspended
• Conditions: Clostridium Difficile; Antibiotic-Associated Diarrhea
• Intervention / Treatment: Drug: loperamide; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • VAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: B; Placebo	Drug: placebo; 4 mg PO initially and 2 mg after each water stoll not to exceed 10 mg qd
Active Comparator: A; Loperamide	Drug: loperamide; 4 mg PO initially and 2 mg after each water stoll not to exceed 10 mg qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determin symptomatic treatment of diarrhea with loperamide in antibiotic associated diarrhea	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To measure the safety and efficacy of loperamide in the control of antibiotic associated diarrhea in hospitalized patients	2 years

Collaborators and Investigators

• Sponsor: Michael E. DeBakey VA Medical Center
• Investigators: Principal Investigator: Daniel M Musher, MD, Michael E. DeBakey VA Medical Center

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: December 31, 2007
• First Submitted That Met QC Criteria: January 10, 2008
• First Posted (Estimate): January 11, 2008

Study Record Updates

• Last Update Posted (Estimate): May 3, 2016
• Last Update Submitted That Met QC Criteria: May 2, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Clostridium difficile; loperamide; Antibiotic associated diarrhea
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Colitis; Clostridium Infections; Gastrointestinal Agents; Loperamide; Antidiarrheals
• Other Study ID Numbers: H-21387; Clostridium difficile; Antibiotic associated diarrhea; loperamide