Efficacy of Metronidazole Versus Metronidazole and Rifampin in CDAD Treatment

NCT00182429 | Completed Phase 3

• 2 other identifiers: 2261Grant Number R03-39 (PSI)
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

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.

Conditions

Clostridium Enterocolitis; Antibiotic-Associated Diarrhea; Pseudomembranous Colitis; Pseudomembranous Enterocolitis; Pseudomembranous Enteritis

Keywords

Antibiotic associated diarrhea; C. difficile; Metronidazole; Rifampin

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (3)

• 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.

Interventions

Metronidazole and Rifampin DRUG

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead
• The Physicians' Services Incorporated Foundation: collaborator

Study Sites (4)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

Location

Henderson General Hospital

Hamilton, Ontario, L8V 1C3, Canada

Location

Related Publications (8)

• 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.

  PMID: 3571889 BACKGROUND

• 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.

  PMID: 8722937 BACKGROUND

• 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.

  PMID: 4043661 BACKGROUND

• 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.

  PMID: 7632199 BACKGROUND

• 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.

  PMID: 3521518 BACKGROUND

• 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.

  PMID: 6138597 BACKGROUND

• 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.

  PMID: 10543736 BACKGROUND

• 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.

  PMID: 1444298 BACKGROUND

MeSH Terms

Conditions

Enterocolitis, Pseudomembranous

Interventions

Metronidazole; Rifampin

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Christine H Lee, MD

  McMaster University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 16, 2005
• Study Start: February 1, 2004
• Primary Completion: April 30, 2005
• Study Completion: December 31, 2005
• Last Updated: August 15, 2018

Record last verified: 2018-08

Locations

CA (4)