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

Study Overview
=================
Brief Summary
-----------------
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).

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.

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

Conditions
-----------------
Clostridium Infections, Diarrhea

Intervention / Treatment
-----------------
* Drug: Rifaximin (Xifaxan)
* Drug: Vancomycin


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clostridium difficile-associated Diarrhea (CDAD), CDAD, C diff