Clostridium Infections, Diarrhea
Conditions
Keywords
Clostridium difficile-associated Diarrhea (CDAD), CDAD, C diff
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.
Interventions
DRUGVancomycin
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rifaximin Treatment Arm rifaximin 400mg taken 3 times a day
Rifaximin (Xifaxan) | 117 |
| Vancomycin Comparator Arm vancomycin 125mg taken 4 times a day
Vancomycing | 115 |
| Total | 232 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 4 |
| Overall Study | Development of exclusion criteria | 0 | 1 |
| Overall Study | Lack of Efficacy | 27 | 10 |
| Overall Study | Negative Lab Result for C. difficile | 2 | 3 |
| Overall Study | Other | 0 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 5 |
Baseline characteristics
| Characteristic | Vancomycin Comparator Arm | Total | Rifaximin Treatment Arm |
|---|---|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 18.08 | 59.5 years STANDARD_DEVIATION 17.14 | 58.9 years STANDARD_DEVIATION 16.22 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 26 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 102 Participants | 205 Participants | 103 Participants |
| Sex: Female, Male Female | 67 Participants | 141 Participants | 74 Participants |
| Sex: Female, Male Male | 48 Participants | 91 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 120 | 2 / 116 |
| serious Total, serious adverse events | 28 / 120 | 14 / 116 |
Outcome results
Primary
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.
Time frame: 14 days
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rifaximin Treatment Arm | 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. | 67 Participants |
| Vancomycin Comparator Arm | 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. | 73 Participants |
Secondary
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.
Time frame: 42 days
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rifaximin Treatment Arm | Proportion of Participants Recurrence-free of Clostridium Difficile-associated Diarrhea (CDAD), After Achieving Clinical Success | 61 Participants |
| Vancomycin Comparator Arm | Proportion of Participants Recurrence-free of Clostridium Difficile-associated Diarrhea (CDAD), After Achieving Clinical Success | 63 Participants |