A Trial to Compare Xifaxan to Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD)
Sponsor
Bausch Health Americas, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00269399
Collaborator
(none)
237
63
2
36
3.8
0.1
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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 Design
Study Type:
Interventional
Actual Enrollment
:
237 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Randomized, Controlled Trial of Rifaximin Compared to Vancomycin for the Treatment of Clostridium Difficile-Associated Diarrhea (CDAD)
Study Start Date
:
Dec 1, 2005
Actual Primary Completion Date
:
Dec 1, 2008
Actual Study Completion Date
:
Dec 1, 2008
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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. [14 days]
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.
Secondary Outcome Measures
- Proportion of Participants Recurrence-free of Clostridium Difficile-associated Diarrhea (CDAD), After Achieving Clinical Success [42 days]
Recurrence of CDAD was defined as diarrhea and a positive Clostridium difficile stool toxin assay that occurs after initial clinical success.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic Scottsdale | Scottsdale | Arizona | United States | 85259 |
| 2 | Inland Empire Digestive & Liver Diseases | Redlands | California | United States | 92373 |
| 3 | Gastroenterology of the Rockies | Longmont | Colorado | United States | 80501 |
| 4 | Connecticut Gastroenterology Institute | Bristol | Connecticut | United States | 06010-0977 |
| 5 | The George Washington University Medical Center | Washington | District of Columbia | United States | 20037 |
| 6 | Halifax Medical Center | Daytona Beach | Florida | United States | 32114 |
| 7 | Advanced Medical Research Center | Port Orange | Florida | United States | 32127 |
| 8 | Webster Surgical Center LLC | Tallahassee | Florida | United States | 32308 |
| 9 | Digestive Healthcare of Georgia | Atlanta | Georgia | United States | 30309 |
| 10 | Southeast Regional Research Group | Columbus | Georgia | United States | 31904 |
| 11 | Sky Blue, M.D. | Boise | Idaho | United States | 83712 |
| 12 | Howard Brown Health Center | Chicago | Illinois | United States | 60613 |
| 13 | The University of Chicago | Chicago | Illinois | United States | 60637 |
| 14 | Gastroenterology, Ltd. | Peoria | Illinois | United States | 61602 |
| 15 | Springfield Clinic | Springfield | Illinois | United States | 62701 |
| 16 | Memorial Medical Center | Springfield | Illinois | United States | 62702 |
| 17 | Carle Clinic Association NCW5 | Urbana | Illinois | United States | 61801 |
| 18 | Iowa Digestive Disease Center, PC | Des Moines | Iowa | United States | 50312-5300 |
| 19 | GI Specialists | Olathe | Kansas | United States | 66061 |
| 20 | Gastrointestinal Associates | Overland Park | Kansas | United States | 66212 |
| 21 | Kansas Medical Clinic | Topeka | Kansas | United States | 66606 |
| 22 | Baltimore VA Medical Center | Baltimore | Maryland | United States | 21201 |
| 23 | University of Maryland | Baltimore | Maryland | United States | 21201 |
| 24 | Chevy Chase Clinical Research | Chevy Chase | Maryland | United States | 20815 |
| 25 | Center for Clinical Research at Washington County Hospital | Hagerstown | Maryland | United States | 21740 |
| 26 | Shah Associates | Prince Frederick | Maryland | United States | 20678 |
| 27 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 28 | Arnold Markowitz, MD, PC | Keego Harbor | Michigan | United States | 48320 |
| 29 | Newland Medical Association | Southfield | Michigan | United States | 48075 |
| 30 | St. Mary's/Duluth Clinic Health System | Duluth | Minnesota | United States | 55805 |
| 31 | Minneapolis VAMC | Minneapolis | Minnesota | United States | 55417 |
| 32 | Infectious Disease - Minneapolis Ltd. | Minneapolis | Minnesota | United States | 55422 |
| 33 | Mayo Clinic Rochester | Rochester | Minnesota | United States | 55905 |
| 34 | Digestive Health Specialists, PA | Tupelo | Mississippi | United States | 38801 |
| 35 | Deaconess Billings Clinic Research | Billings | Montana | United States | 59101 |
| 36 | Infectious Diseases Associates, PC | Omaha | Nebraska | United States | 68114 |
| 37 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 38 | Drs. Scherl, Chessler, Zingler, Spinnel and Meininger | Fort Lee | New Jersey | United States | 07024 |
| 39 | Marlboro Gastroenterology PC | Manalapan | New Jersey | United States | 07726 |
| 40 | St. Michael's Medical Center | Newark | New Jersey | United States | 07102 |
| 41 | Institute for Clinical Research (ICR) at Holy Name Hospital | Teaneck | New Jersey | United States | 07666 |
| 42 | The Gastroenterology Group of South Jersey | Vineland | New Jersey | United States | 08360 |
| 43 | Brookdale University Hospital and Medical Center | Brooklyn | New York | United States | 11212 |
| 44 | AMS Clinical Research | Elmira | New York | United States | 14905 |
| 45 | North Shore Hepatology | Manhasset | New York | United States | 11030 |
| 46 | Weill Medical College | New York | New York | United States | 10021 |
| 47 | University of Rochester School of Medicine | Rochester | New York | United States | 14642 |
| 48 | New York Medical College/Westchester Medical Center | Valhalla | New York | United States | 10595 |
| 49 | East Carolina Gastroenterology, PA | Jacksonville | North Carolina | United States | 28546 |
| 50 | Southern Gastroenterology Associates | New Bern | North Carolina | United States | 28562 |
| 51 | University of Cincinnati | Cincinnati | Ohio | United States | 45267-0595 |
| 52 | Regional Infectious Diseases - Infusion Center | Lima | Ohio | United States | 45801 |
| 53 | Lima Memorial Health System | Lima | Ohio | United States | 45804 |
| 54 | Lehigh Valley Hospital | Allentown | Pennsylvania | United States | 18103 |
| 55 | Drexel University College of Medicine | Philadelphia | Pennsylvania | United States | 19107 |
| 56 | RPS Infectious Diseases | West Reading | Pennsylvania | United States | 19611 |
| 57 | University Gastroenterology | Providence | Rhode Island | United States | 02905 |
| 58 | Digestive Disease Associates of Dallas | Dallas | Texas | United States | 75231 |
| 59 | Michael E. DeBakey VA Medical Center | Houston | Texas | United States | 77030 |
| 60 | University of Texas Health Sciences Center | Houston | Texas | United States | 77030 |
| 61 | Infectious Disease Associates of Central Virginia | Lynchburg | Virginia | United States | 24501 |
| 62 | North Pacific Clinical Research | Redmond | Washington | United States | 98052 |
| 63 | Associated Physicians, LLP | Madison | Wisconsin | United States | 53705 |
Sponsors and Collaborators
- Bausch Health Americas, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Bausch Health Americas, Inc.
ClinicalTrials.gov Identifier:
NCT00269399
Other Study ID Numbers:
- RFCL3001
First Posted:
Dec 23, 2005
Last Update Posted:
Oct 14, 2019
Last Verified:
Sep 1, 2019
Keywords provided by Bausch Health Americas, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Rifaximin Treatment Arm | Vancomycin Comparator Arm |
|---|---|---|
| Arm/Group Description | rifaximin 400mg taken 3 times a day Rifaximin (Xifaxan) | vancomycin 125mg taken 4 times a day |
| Period Title: Overall Study | ||
| STARTED | 119 | 118 |
| COMPLETED | 78 | 91 |
| NOT COMPLETED | 41 | 27 |
Baseline Characteristics
| Arm/Group Title | Rifaximin Treatment Arm | Vancomycin Comparator Arm | Total |
|---|---|---|---|
| Arm/Group Description | rifaximin 400mg taken 3 times a day Rifaximin (Xifaxan) | vancomycin 125mg taken 4 times a day Vancomycing | Total of all reporting groups |
| Overall Participants | 117 | 115 | 232 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58.9
(16.22)
|
60.0
(18.08)
|
59.5
(17.14)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
74
63.2%
|
67
58.3%
|
141
60.8%
|
| Male |
43
36.8%
|
48
41.7%
|
91
39.2%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
0.9%
|
1
0.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
14
12%
|
12
10.4%
|
26
11.2%
|
| White |
103
88%
|
102
88.7%
|
205
88.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | 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. |
|---|---|
| Description | 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. |
| Time Frame | 14 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent-to-Treat (MITT) population included all randomized subjects who had acute diarrhea and with a positive C. difficile stool toxin assay within ± 48 hours of screening and received at least one dose of study drug. |
| Arm/Group Title | Rifaximin Treatment Arm | Vancomycin Comparator Arm |
|---|---|---|
| Arm/Group Description | rifaximin 400mg taken 3 times a day Rifaximin (Xifaxan) | vancomycin 125mg taken 4 times a day Vancomycin |
| Measure Participants | 117 | 115 |
| Count of Participants [Participants] |
67
57.3%
|
73
63.5%
|
| Title | Proportion of Participants Recurrence-free of Clostridium Difficile-associated Diarrhea (CDAD), After Achieving Clinical Success |
|---|---|
| Description | Recurrence of CDAD was defined as diarrhea and a positive Clostridium difficile stool toxin assay that occurs after initial clinical success. |
| Time Frame | 42 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants included in this analysis were restricted to those who experienced initial clinical success at the TOC Visit following the 10-day Treatment Phase. |
| Arm/Group Title | Rifaximin Treatment Arm | Vancomycin Comparator Arm |
|---|---|---|
| Arm/Group Description | rifaximin 400mg taken 3 times a day Rifaximin (Xifaxan) | vancomycin 125mg taken 4 times a day Vancomycin |
| Measure Participants | 67 | 73 |
| Count of Participants [Participants] |
61
52.1%
|
63
54.8%
|
Adverse Events
| Time Frame | 42 days | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | For safety analyses participants are counted based on the treatments received rather than randomization assignment; 120 participants in the rifaximin group and 116 participants in the vancomycin group. Two (2) participants in the vancomycin group are handled differently than as randomized, including 1 participant who did not receive study drug (so excluded from the safety population) and 1 participant counted in the rifaximin group for safety since the subject actually received rifaximin. | |||
| Arm/Group Title | Rifaximin Treatment Arm | Vancomycin Comparator Arm | ||
| Arm/Group Description | rifaximin 400mg taken 3 times a day Rifaximin (Xifaxan) | vancomycin 125mg taken 4 times a day | ||
All Cause Mortality |
||||
| Rifaximin Treatment Arm | Vancomycin Comparator Arm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Rifaximin Treatment Arm | Vancomycin Comparator Arm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 28/120 (23.3%) | 14/116 (12.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 1/120 (0.8%) | 1/116 (0.9%) | ||
| Anemia hemolytic autoimmune | 1/120 (0.8%) | 0/116 (0%) | ||
| Leukocytosis | 0/120 (0%) | 1/116 (0.9%) | ||
| Thrombocytopenia | 0/120 (0%) | 1/116 (0.9%) | ||
| Cardiac disorders | ||||
| Cardio-respiratory arrest | 1/120 (0.8%) | 1/116 (0.9%) | ||
| Cardio-respiratory arrest | 1/120 (0.8%) | 0/116 (0%) | ||
| Cardiac failure congestive | 0/120 (0%) | 1/116 (0.9%) | ||
| Coronary artery disease | 0/120 (0%) | 1/116 (0.9%) | ||
| Tachycardia | 0/120 (0%) | 1/116 (0.9%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 4/120 (3.3%) | 0/116 (0%) | ||
| Diarrhea | 3/120 (2.5%) | 3/116 (2.6%) | ||
| Abdominal discomfort | 0/120 (0%) | 1/116 (0.9%) | ||
| Colitis ulcerative | 1/120 (0.8%) | 0/116 (0%) | ||
| Duodenal ulcer | 1/120 (0.8%) | 0/116 (0%) | ||
| Pancreatitis | 0/120 (0%) | 1/116 (0.9%) | ||
| Umbilical hernia | 1/120 (0.8%) | 0/116 (0%) | ||
| Upper gastrointestinal hemorrhage | 1/120 (0.8%) | 0/116 (0%) | ||
| Vomiting | 0/120 (0%) | 1/116 (0.9%) | ||
| General disorders | ||||
| Pyrexia | 1/120 (0.8%) | 1/116 (0.9%) | ||
| Chest pain | 0/120 (0%) | 1/116 (0.9%) | ||
| Infections and infestations | ||||
| Clostridial infection | 2/120 (1.7%) | 1/116 (0.9%) | ||
| Clostridium colitis | 2/120 (1.7%) | 0/116 (0%) | ||
| Pneumonia | 0/120 (0%) | 2/116 (1.7%) | ||
| Asymptomatic bacteriuria | 1/120 (0.8%) | 0/116 (0%) | ||
| Bacteremia | 1/120 (0.8%) | 0/116 (0%) | ||
| Cellulitis | 1/120 (0.8%) | 0/116 (0%) | ||
| Klebsiella sepsis | 1/120 (0.8%) | 0/116 (0%) | ||
| Pseudomonas infection | 1/120 (0.8%) | 0/116 (0%) | ||
| Sepsis | 0/120 (0%) | 1/116 (0.9%) | ||
| Urinary tract infection | 1/120 (0.8%) | 0/116 (0%) | ||
| Urosepsis | 0/120 (0%) | 1/116 (0.9%) | ||
| Wound infection | 1/120 (0.8%) | 0/116 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Collapse of lung | 0/120 (0%) | 1/116 (0.9%) | ||
| Seroma | 0/120 (0%) | 1/116 (0.9%) | ||
| Investigations | ||||
| Blood creatinine increased | 1/120 (0.8%) | 0/116 (0%) | ||
| Blood urea increased | 1/120 (0.8%) | 0/116 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 3/120 (2.5%) | 4/116 (3.4%) | ||
| Electrolyte imbalance | 1/120 (0.8%) | 0/116 (0%) | ||
| Hyperglycemia | 0/120 (0%) | 1/116 (0.9%) | ||
| Hyperkalemia | 1/120 (0.8%) | 0/116 (0%) | ||
| Hypokalemia | 1/120 (0.8%) | 0/116 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Colon cancer | 0/120 (0%) | 1/116 (0.9%) | ||
| Lung meoplasm malignant | 1/120 (0.8%) | 0/116 (0%) | ||
| Neuroendocrine carcinoma | 1/120 (0.8%) | 0/116 (0%) | ||
| Non-small cell lung cancer | 1/120 (0.8%) | 0/116 (0%) | ||
| Non-small cell lung cancer metastatic | 1/120 (0.8%) | 0/116 (0%) | ||
| Renal cell carcinoma stage unspecified | 1/120 (0.8%) | 0/116 (0%) | ||
| Nervous system disorders | ||||
| Aphasia | 1/120 (0.8%) | 0/116 (0%) | ||
| Psychiatric disorders | ||||
| Mental status changes | 0/120 (0%) | 2/116 (1.7%) | ||
| Suicide attempt | 1/120 (0.8%) | 0/116 (0%) | ||
| Renal and urinary disorders | ||||
| Renal failure acute | 3/120 (2.5%) | 2/116 (1.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chromic obstructive pulmonary disease | 0/120 (0%) | 1/116 (0.9%) | ||
| Dyspnea | 1/120 (0.8%) | 0/116 (0%) | ||
| Hydopneumothorax | 0/120 (0%) | 1/116 (0.9%) | ||
| Vascular disorders | ||||
| Hypotension | 3/120 (2.5%) | 2/116 (1.7%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Rifaximin Treatment Arm | Vancomycin Comparator Arm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/120 (5%) | 2/116 (1.7%) | ||
| Psychiatric disorders | ||||
| Insomnia | 6/120 (5%) | 2/116 (1.7%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Please contact sponsor for details.
Results Point of Contact
| Name/Title | Director of Clinical Operations |
|---|---|
| Organization | Bausch Health Americas, Inc. |
| Phone | 908-927-0873 |
| lindsey.mathew@bauschhealth.com |
Responsible Party:
Bausch Health Americas, Inc.
ClinicalTrials.gov Identifier:
NCT00269399
Other Study ID Numbers:
- RFCL3001
First Posted:
Dec 23, 2005
Last Update Posted:
Oct 14, 2019
Last Verified:
Sep 1, 2019