A Trial to Compare Xifaxan to Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD)

A Double-Blind, Randomized, Controlled Trial of Rifaximin Compared to Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD)

The purpose of this study is to assess the treatment and safety of a 10-day course of rifaximin (Xifaxan) as compared to vancomycin for treatment of Clostridium difficile-associated diarrhea (CDAD).

Study Overview

• Status: Completed
• Conditions: Diarrhea; Clostridium Infections
• Intervention / Treatment: Drug: Vancomycin; Drug: Rifaximin (Xifaxan)

Detailed Description

Clostridium difficile is a bacterium that proliferates when normal colonic flora have been altered, most commonly due to antibiotic use. Clostridium difficile is non-invasive and localized to the lumen of the colon. Once established, it produces 2 potent toxins, A and B. The principal reservoir for Clostridium difficile is the hospital environment, with the risk of acquiring Clostridium difficile increasing in direct proportion to the length of hospital stay.

Patients with CDAD typically present with profuse watery or mucoid diarrhea and cramping abdominal pain. Additional symptoms include fever, nausea, anorexia, malaise, and bloody stool. More severe cases may be complicated by dehydration, electrolyte disturbances, ileus, and peritonitis. Systemic manifestations may include prerenal azotemia, sepsis syndrome, and toxic colitis. White blood cell counts (WBCs) also may be markedly elevated with a shift to immature forms. Extreme presentation of fulminant colitis may require a colectomy and even result in death. Symptoms of CDAD may begin a few days after initiation of antibiotic therapy or up to 8 weeks after its discontinuation.

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • California
    • Redlands, California, United States, 92373
      • Inland Empire Digestive & Liver Diseases
  • Colorado
    • Longmont, Colorado, United States, 80501
      • Gastroenterology of the Rockies
  • Connecticut
    • Bristol, Connecticut, United States, 06010-0977
      • Connecticut Gastroenterology Institute
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • The George Washington University Medical Center
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Halifax Medical Center
    • Port Orange, Florida, United States, 32127
      • Advanced Medical Research Center
    • Tallahassee, Florida, United States, 32308
      • Webster Surgical Center LLC
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Digestive Healthcare of Georgia
    • Columbus, Georgia, United States, 31904
      • Southeast Regional Research Group
  • Idaho
    • Boise, Idaho, United States, 83712
      • Sky Blue, M.D.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
    • Peoria, Illinois, United States, 61602
      • Gastroenterology, Ltd.
    • Springfield, Illinois, United States, 62702
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62701
      • Springfield Clinic
    • Urbana, Illinois, United States, 61801
      • Carle Clinic Association NCW5
  • Iowa
    • Des Moines, Iowa, United States, 50312-5300
      • Iowa Digestive Disease Center, PC
  • Kansas
    • Olathe, Kansas, United States, 66061
      • GI Specialists
    • Overland Park, Kansas, United States, 66212
      • Gastrointestinal Associates
    • Topeka, Kansas, United States, 66606
      • Kansas Medical Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21201
      • Baltimore VA Medical Center
    • Chevy Chase, Maryland, United States, 20815
      • Chevy Chase Clinical Research
    • Hagerstown, Maryland, United States, 21740
      • Center for Clinical Research at Washington County Hospital
    • Prince Frederick, Maryland, United States, 20678
      • Shah Associates
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Keego Harbor, Michigan, United States, 48320
      • Arnold Markowitz, MD, PC
    • Southfield, Michigan, United States, 48075
      • Newland Medical Association
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • St. Mary's/Duluth Clinic Health System
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VAMC
    • Minneapolis, Minnesota, United States, 55422
      • Infectious Disease - Minneapolis Ltd.
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Digestive Health Specialists, PA
  • Montana
    • Billings, Montana, United States, 59101
      • Deaconess Billings Clinic Research
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Infectious Diseases Associates, PC
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Fort Lee, New Jersey, United States, 07024
      • Drs. Scherl, Chessler, Zingler, Spinnel and Meininger
    • Manalapan, New Jersey, United States, 07726
      • Marlboro Gastroenterology PC
    • Newark, New Jersey, United States, 07102
      • St. Michael's Medical Center
    • Teaneck, New Jersey, United States, 07666
      • Institute for Clinical Research (ICR) at Holy Name Hospital
    • Vineland, New Jersey, United States, 08360
      • The Gastroenterology Group of South Jersey
  • New York
    • Brooklyn, New York, United States, 11212
      • Brookdale University Hospital and Medical Center
    • Elmira, New York, United States, 14905
      • AMS Clinical Research
    • Manhasset, New York, United States, 11030
      • North Shore Hepatology
    • New York, New York, United States, 10021
      • Weill Medical College
    • Rochester, New York, United States, 14642
      • University of Rochester School of Medicine
    • Valhalla, New York, United States, 10595
      • New York Medical College/Westchester Medical Center
  • North Carolina
    • Jacksonville, North Carolina, United States, 28546
      • East Carolina Gastroenterology, PA
    • New Bern, North Carolina, United States, 28562
      • Southern Gastroenterology Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0595
      • University of Cincinnati
    • Lima, Ohio, United States, 45801
      • Regional Infectious Diseases - Infusion Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Health System
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • LeHigh Valley Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Drexel University College of Medicine
    • West Reading, Pennsylvania, United States, 19611
      • RPS Infectious Diseases
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • University Gastroenterology
  • Texas
    • Dallas, Texas, United States, 75231
      • Digestive Disease Associates of Dallas
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas Health Sciences Center
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Infectious Disease Associates of Central Virginia
  • Washington
    • Redmond, Washington, United States, 98052
      • North Pacific Clinical Research
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Associated Physicians, LLP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is 18 years of age or older, has acute diarrhea and at least 1 other sign of enteric infection present, such as fever, nausea/loss of appetite, vomiting, severe abdominal pain or discomfort.
• Subject has a positive Clostridium difficile stool toxin assay at screening

Exclusion Criteria:

• Subject has had a previous episode of clinically diagnosed Clostridium difficile within the past 6 months.
• Subject has chronic diseases associated with diarrhea (e.g., inflammatory bowel disease or diarrhea predominant irritable bowel syndrome [DIBS])
• Subject has had any therapy with any agent administered for the treatment of Clostridium difficile prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rifaximin Treatment Arm; rifaximin 400mg taken 3 times a day	Drug: Rifaximin (Xifaxan)
Active Comparator: Vancomycin Comparator Arm; vancomycin 125mg taken 4 times a day	Drug: Vancomycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Achieving Clinical Success, Where Clinical Success is Defined as Resolution or Improvement of Baseline Signs and Symptoms i.e., Abdominal Pain, Fever, Diarrhea.	Resolution or improvement of baseline signs and symptoms was assessed as; Absence of severe abdominal pain for 2 consecutive days at the test of cure (TOC) Visit (Day 14 +/-1);; Absence of fever (< 38°C/100.4°F) for 2 consecutive days at the TOC Visit; and; 3 unformed (loose or watery) stools per day for at least 48 hours that was sustained through the TOC Visit.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Recurrence-free of Clostridium Difficile-associated Diarrhea (CDAD), After Achieving Clinical Success	Recurrence of CDAD was defined as diarrhea and a positive Clostridium difficile stool toxin assay that occurs after initial clinical success.	42 days

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: December 22, 2005
• First Submitted That Met QC Criteria: December 22, 2005
• First Posted (Estimate): December 23, 2005

Study Record Updates

• Last Update Posted (Actual): October 14, 2019
• Last Update Submitted That Met QC Criteria: September 30, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: CDAD; C diff; Clostridium difficile-associated Diarrhea (CDAD)
• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin; Vancomycin
• Other Study ID Numbers: RFCL3001