Clostridium Infections, Diarrhea
Conditions
Keywords
Bio-K+CL1285, Probiotics, Antibiotics-associated diarrhea, Clostridium difficile-associated diarrhea, Lactobacillus acidophilus, Clostridium Difficile
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Bio-K + CL1285 versus placebo in the prevention of antibiotic-associated diarrhea in hospitalized adult patients.
Detailed description
Antibiotic-associated diarrhea (AAD) is one of the most frequent adverse events following antibiotherapy and is the leading cause of diarrhea in hospitalized patients. Ten to 25% of AAD are caused by the bacteria Clostridium difficile. A recent unicenter study conducted at Maisonneuve-Rosemont hospital demonstrated the preventive role of Bio-K + CL1285 in antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea. Its preventive role is thought to be mainly through restoration of the gastrointestinal flora affected in part by the antibiotherapy. A wide body of literature reveals clinical use of probiotics, but few well controlled prospective studies conducted on large numbers of subjects have been performed. In light of the positive preliminary results obtained in a limited number of patients with AAD and of the paucity of well controlled clinical trials, we now wish to undertake a randomized, double blind, multicentre study to evaluate the efficacy and safety of Bio-K + CL1285 prophylaxis vs. placebo in the prevention of antibiotic-associated diarrhea in hospitalized adult patients. As secondary objectives, we also intend to evaluate the incidence of Clostridium difficile-associated diarrhea and to demonstrate that BIO-K + CL1285 agent will not only improve the clinical outcomes but also reduce health care expenditures.
Interventions
DIETARY_SUPPLEMENTLactobacillus acidophilus CL1285 and Lactobacillus casei
One bottle daily 2 hours before or after antibiotic administration and for 5 days following the termination of antibiotic regimen.
DIETARY_SUPPLEMENTplacebo
One bottle daily 2 hours before or after antibiotic administration and for 5 days following the termination of antibiotic regimen.
Sponsors
JSS Medical Research Inc.
Bio-K Plus International Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* presenting to the Emergency Room and considered for admission to hospital for a minimum of 12 hours and requiring antibiotic administration for the treatment of a suspected or proven bacterial infection OR a hospitalized patient developing a suspected or proven nosocomial infection OR an external patient that come to the hospital for repeated visits to receive his intravenous antibiotic therapy for the treatment of a suspected or proven bacterial infection. The external patients on oral antibiotics that come to the hospital for repeated visits to receive any other treatments requiring a hospital stay of more than one hour will also be included. * Hospital employee on antibiotics can also be included in the study * having received less than 24 hours of antibiotic therapy; * requiring a minimum of 3 days and a maximum of 14 days antibiotic administration Informed consent must be obtained in writing for all subjects at enrollment into the study
Exclusion criteria
Subjects presenting with any of the following will not be included in the study: * active diarrhea; * a history of daily consumption of fermented milk and/or yogurt; * intolerance to lactose; * pregnant/breastfeeding women; * an active, non controlled intestinal disease such as Crohn's Disease or ulcerative colitis; * ileostomy, jejunostomy or colostomy; * immunosuppressed state; * a previous documented C. difficile infection in the three months prior to study initiation; * active radiotherapy or chemotherapy; * recent (\< 6 months) or planned bone marrow graft or organ transplant; * antibiotic therapy in the fourteen days prior to study initiation; * the planned administration of metronidazole (alone or in combination) or vancomycin monotherapy for the treatment of an infection; * mental or other conditions, or language barriers rendering the subject unable to understand the nature, scope, and possible consequences of the study or complete the self-administered questionnaires; * subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study. Post-enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Antibiotic-associated Diarrhea. | Up to 40 days | Presence of at least one diarrhea episode within 24 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive Results for Clostridium Difficile (C. Difficile) Toxin A or B in Antibiotic Associated Diarrhea Patients. | Up to 40 days | Testing for CDAD was performed at the discretion of the treating physician and according to the protocol in place at the study centers. CDAD was defined as an episode of diarrhea and positive results for C. difficile Toxin A or B. |
| Health Outcome Evaluation Will Look at the Direct Medical Costs and Clinical Outcomes of Alternative Strategies in the Prevention of Antibiotic-associated Diarrhea in Hospitalized Adult Patients | Up to 40 days | — |
| Safety Profile of BIO-K+CL1285® Versus Placebo in Patients on Antibiotics | Up to 40 days | Safety was assessed by the incidence of treatment-emerged adverse events, which were reported according to MedDRA 10.1 |
Countries
Canada
Participant flow
Recruitment details
2151 patients were screened for eligibility. 437 patients were randomized for the study between March 2006 and October 2006.
Pre-assignment details
Inclusion & exclusion criterias were used to randomized patients. Patients were followed for an additionnal 21 days after treatment ended.
Participants by arm
| Arm | Count |
|---|---|
| Bio-K+ CL1285 98g/day of Bio-K+ CL1285 containing 50 billion of live bacteria. | 216 |
| Placebo 98g/day of placebo (devoid of microorganisms) | 221 |
| Total | 437 |
Baseline characteristics
| Characteristic | Bio-K+ CL1285 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 18.1 | 58.1 years STANDARD_DEVIATION 19.1 | 58.8 years STANDARD_DEVIATION 18.6 |
| Region of Enrollment Canada | 216 participants | 221 participants | 437 participants |
| Sex: Female, Male Female | 99 Participants | 114 Participants | 213 Participants |
| Sex: Female, Male Male | 117 Participants | 107 Participants | 224 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 109 / 216 | 113 / 221 |
| serious Total, serious adverse events | 15 / 216 | 23 / 221 |
Outcome results
Primary
The Incidence of Antibiotic-associated Diarrhea.
Presence of at least one diarrhea episode within 24 hours.
Time frame: Up to 40 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bio-K+ CL1285 | The Incidence of Antibiotic-associated Diarrhea. | 216 participants |
| Placebo | The Incidence of Antibiotic-associated Diarrhea. | 221 participants |
Secondary
Health Outcome Evaluation Will Look at the Direct Medical Costs and Clinical Outcomes of Alternative Strategies in the Prevention of Antibiotic-associated Diarrhea in Hospitalized Adult Patients
Time frame: Up to 40 days
Secondary
Positive Results for Clostridium Difficile (C. Difficile) Toxin A or B in Antibiotic Associated Diarrhea Patients.
Testing for CDAD was performed at the discretion of the treating physician and according to the protocol in place at the study centers. CDAD was defined as an episode of diarrhea and positive results for C. difficile Toxin A or B.
Time frame: Up to 40 days
Secondary
Safety Profile of BIO-K+CL1285® Versus Placebo in Patients on Antibiotics
Safety was assessed by the incidence of treatment-emerged adverse events, which were reported according to MedDRA 10.1
Time frame: Up to 40 days