Efficacy of Metronidazole Versus Metronidazole and Rifampin in CDAD Treatment
Information source: McMaster University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Clostridium Enterocolitis; Antibiotic-Associated Diarrhea; Pseudomembranous Colitis; Pseudomembranous Enterocolitis; Pseudomembranous Enteritis
Intervention: Metronidazole and Rifampin (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Hamilton Health Sciences Corporation Official(s) and/or principal investigator(s):
Danny Lagrotteria, MD, Principal Investigator, Affiliation: McMaster University
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.
Clinical Details
Official title: Prospective, Randomized Study of Oral Metronidazole Vs. Oral Metronidazole and Rifampin for Treatment of Clostridium Difficile-Associated Diarrhea (CDAD)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: Resolution of symptoms in each treatment arm (in days) up to 40 days (measured using daily stool and symptom diary).
Secondary outcome: 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.
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
Minimum age: 14 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Hamilton General Hospital, Hamilton, Ontario L8L 2X2, Canada
Henderson General Hospital, Hamilton, Ontario L8V 1C3, Canada
McMaster University Medical Centre, Hamilton, Ontario L8N 3Z5, Canada
St. Joseph's Healthcare, Hamilton, Ontario L8N 4A6, Canada
Additional Information
Related 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, 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. 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, 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. 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.
Starting date: February 2004
Last updated: February 15, 2006
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