Clinical trial NCT00182429: Efficacy of Metronidazole Versus Metronidazole and Rifampin in CDAD Treatment
Official title: Prospective, Randomized Study of Oral Metronidazole vs. Oral Metronidazole and Rifampin for Treatment of Clostridium Difficile-associated Diarrhea (CDAD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridium Enterocolitis
Antibiotic-Associated Diarrhea
Pseudomembranous Colitis
Pseudomembranous Enterocolitis
Pseudomembranous Enteritis
Keywords: Antibiotic associated diarrhea
C. difficile
Metronidazole
Rifampin
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: The Physicians' Services Incorporated Foundation
First posted: 2005-09-16
Enrollment: 100
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Resolution of symptoms in each treatment arm (in days) up to 40 days (measured using daily stool and symptom diary).
Secondary outcomes:
measure: 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).
measure: Adverse reactions related to treatment within 40 days (measured using daily symptom diary and interviewing patient).
measure: Occurrance of metronidazole resistance in the organism (C. difficile) in relapse cases.
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: Hamilton
country: Canada
facility: Henderson General Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Christine H Lee, MD
role: STUDY_DIRECTOR
References:
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. doi: 10.1097/00004836-198704000-00009.
citation: 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. doi: 10.1093/clinids/22.5.813.
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. doi: 10.1016/0016-5085(85)90206-9.
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. doi: 10.1086/646934.
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.
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. doi: 10.1016/s0140-6736(83)91036-x.
citation: 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. doi: 10.1128/AAC.43.11.2607.
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. doi: 10.1128/AAC.36.10.2192.