Efficacy of Metronidazole Versus Metronidazole and Rifampin in CDAD Treatment

Antibiotic-Associated Diarrhea Clinical Trial

Official title:

Prospective, Randomized Study of Oral Metronidazole vs. Oral Metronidazole and Rifampin for Treatment of Clostridium Difficile-associated Diarrhea (CDAD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00182429
• Other study ID #: 2261
• Secondary ID: Grant Number R03
• Status: Completed
• Phase: Phase 3
• Start date: February 2004
• Est. completion date: December 31, 2005

Study information

• Verified date: August 2018
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 31, 2005
• Est. primary completion date: April 30, 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Antibiotic-Associated Diarrhea
• Clostridium Enterocolitis
• Diarrhea
• Enteritis
• Enterocolitis
• Enterocolitis, Pseudomembranous
• Pseudomembranous Colitis
• Pseudomembranous Enteritis
• Pseudomembranous Enterocolitis

Intervention

Drug:
• Metronidazole and Rifampin

Locations

Country	Name	City	State
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Henderson General Hospital	Hamilton	Ontario
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	St. Joseph's Healthcare	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	The Physicians' Services Incorporated Foundation

Country where clinical trial is conducted

Canada, 

References & Publications (8)

Barbut F, Decré D, Burghoffer B, Lesage D, Delisle F, Lalande V, Delmée 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Wenisch C, Parschalk B, Hasenhündl 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resolution of symptoms in each treatment arm (in days) up to 40 days (measured using daily stool and symptom diary).
Secondary	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).
Secondary	Adverse reactions related to treatment within 40 days (measured using daily symptom diary and interviewing patient).
Secondary	Occurrance of metronidazole resistance in the organism (C. difficile) in relapse cases.