Efficacy of Metronidazole Versus Metronidazole and Rifampin in CDAD Treatment - Full Text View

Sponsor:	Hamilton Health Sciences Corporation
Collaborator:	The Physicians' Services Incorporated Foundation
Information provided by:	McMaster University
ClinicalTrials.gov Identifier:	NCT00182429

Purpose

What is the difference between the use of one drug (Oral Metronidazole) versus the use of this same drug combined with another drug (Rifampin) in treatment of bacteria and infection-associated diarrhea in patients? This infection is an important cause of morbidity and mortality in both the community and hospitals, and the leading cause of hospital and chronic facility-acquired diarrhea. Research is important for the treatment of this infection. Patient care with use of two medication treatment regimens will be studied.

Condition	Intervention	Phase
Clostridium Enterocolitis Antibiotic-Associated Diarrhea Pseudomembranous Colitis Pseudomembranous Enterocolitis Pseudomembranous Enteritis	Drug: Metronidazole and Rifampin	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	Prospective, Randomized Study of Oral Metronidazole Vs. Oral Metronidazole and Rifampin for Treatment of Clostridium Difficile-Associated Diarrhea (CDAD)

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Diarrhea

Drug Information available for: Rifampin Metronidazole hydrochloride Metronidazole phosphate Metronidazole

U.S. FDA Resources

Further study details as provided by McMaster University:

Primary Outcome Measures:

Resolution of symptoms in each treatment arm (in days) up to 40 days (measured using daily stool and symptom diary).

Secondary Outcome Measures:

Clinical relapse rate in each group (time to relapse in days) up to 40 days after initial diagnosis (measured by repeating C. difficile toxin assay and analyzing daily stool and symptom diary).
Adverse reactions related to treatment within 40 days (measured using daily symptom diary and interviewing patient).
Occurrance of metronidazole resistance in the organism (C. difficile) in relapse cases.

Estimated Enrollment:	100
Study Start Date:	February 2004
Estimated Study Completion Date:	April 2005

Detailed Description:

Clostridium difficile infection contributes to both community and hospital acquired morbidity and mortality. Metronidazole alone is usually considered the drug of choice, however, frequent relapses occur at a rate of 10-40%. The purpose of this study is to address the use of a combined drug regimen treatment (Metronidazole and Rifampin) for the treatment of CDAD. These drugs used together have been successful. Objectives are to determine the time (days) to resolution of symptoms in each treatment arm; to measure clinical relapse rates; and to assess adverse reactions related to treatment.

Eligibility

Ages Eligible for Study:	14 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Inpatients + outpatients diagnosed with CDAD based on SHEA definition [Laboratory confirmation for presence of C.difficile toxin using enzyme immunoassay and no other etiology for diarrhea + Presence of 1 or more of the following: diarrhea (6 watery stool over 36 hours or 3 unformed stools in 24 hours for at least 2days), pseudomembranes at endoscopy].

Exclusion Criteria:

Age < 14 yr
Known hypersensitivity to metronidazole, rifampin
Receiving medication(s) with potential significant drug interaction with rifampin
Active liver disease as indicated by ALT > 200 U/L
Adynamic ileus
Toxic megacolon
Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00182429

Locations

Canada, Ontario
St. Joseph's Healthcare
Hamilton, Ontario, Canada, L8N 4A6
McMaster University Medical Centre
Hamilton, Ontario, Canada, L8N 3Z5
Hamilton General Hospital
Hamilton, Ontario, Canada, L8L 2X2
Henderson General Hospital
Hamilton, Ontario, Canada, L8V 1C3

Sponsors and Collaborators

Hamilton Health Sciences Corporation

The Physicians' Services Incorporated Foundation

Investigators

Principal Investigator:

Danny Lagrotteria, MD

McMaster University

More Information

Publications:

Buggy BP, Fekety R, Silva J Jr. Therapy of relapsing Clostridium difficile-associated diarrhea and colitis with the combination of vancomycin and rifampin. J Clin Gastroenterol. 1987 Apr;9(2):155-9.

Wenisch C, Parschalk B, Hasenhundl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996 May;22(5):813-8. Erratum in: Clin Infect Dis 1996 Aug;23(2):423.

Young GP, Ward PB, Bayley N, Gordon D, Higgins G, Trapani JA, McDonald MI, Labrooy J, Hecker R. Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin. Gastroenterology. 1985 Nov;89(5):1038-45.

Olson MM, Shanholtzer CJ, Lee JT Jr, Gerding DN. Ten years of prospective Clostridium difficile-associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982-1991. Infect Control Hosp Epidemiol. 1994 Jun;15(6):371-81.

Dudley MN, McLaughlin JC, Carrington G, Frick J, Nightingale CH, Quintiliani R. Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea. A randomized double-blind trial. Arch Intern Med. 1986 Jun;146(6):1101-4.

Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ, Lee JT Jr. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet. 1983 Nov 5;2(8358):1043-6.

Barbut F, Decre D, Burghoffer B, Lesage D, Delisle F, Lalande V, Delmee M, Avesani V, Sano N, Coudert C, Petit JC. Antimicrobial susceptibilities and serogroups of clinical strains of Clostridium difficile isolated in France in 1991 and 1997. Antimicrob Agents Chemother. 1999 Nov;43(11):2607-11.

de Lalla F, Nicolin R, Rinaldi E, Scarpellini P, Rigoli R, Manfrin V, Tramarin A. Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile-associated diarrhea. Antimicrob Agents Chemother. 1992 Oct;36(10):2192-6.

ClinicalTrials.gov Identifier:	NCT00182429 History of Changes
Other Study ID Numbers:	2261, Grant Number R03-39 (PSI)
Study First Received:	September 13, 2005
Last Updated:	February 15, 2006
Health Authority:	Canada: Health Canada

Keywords provided by McMaster University:

Antibiotic associated diarrhea
C. difficile
Metronidazole
Rifampin

Additional relevant MeSH terms:

Colitis
Diarrhea
Enteritis
Enterocolitis
Enterocolitis, Pseudomembranous
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Clostridium Infections
Gram-Positive Bacterial Infections
Bacterial Infections

Metronidazole
Rifampin
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses
Antiprotozoal Agents
Antiparasitic Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents

ClinicalTrials.gov processed this record on February 09, 2012