Antibiotic-Associated Diarrhea, Clostridium Difficile-Associated Diarrhea
Conditions
Keywords
Probiotic, Antibiotic-Associated Diarrhea (AAD) Prevention, Clostridium Difficile-Associated Diarrhea (CDAD)Prevention
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Bio-K+ CL-1285 in the prevention of Antibiotic-Associated Diarrhea (AAD) and Clostridum difficile-Associated Diarrhea (CDAD) in hospitalized patients exposed to nosocomial infection.
Interventions
OTHERBIO-K+ CL-1285®
A mixture of Lactobacillus acidophilus and Lactobacillus casei, contains over 50 billion living bacteria per administered dose.
OTHERPlacebo
Placebo is devoid of microorganisms.
Sponsors
Sprim Advanced Life Sciences
Bio-K Plus International Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Antibiotic therapy for a minimum of 3 days and a maximum of 14 days * Expected to remain hospitalized for a minimum of 5 days * Patients who have received less than 36 hours of antibiotic therapy * Negative pregnancy test at screening * Obtained his/her informed consent after verbal and written information * Patients having a telephone available (mobile, work, home) * Patients having a fridge at home
Exclusion criteria
* Pregnant or breastfeeding women * Patients presenting with active diarrhea (3 or more liquid stools per 24 hour period). * Patients with a history of daily consumption of probiotics, fermented milk and/or yogurt; * Patients known to have shown a previous reaction, including anaphylaxis, to any substance in composition of the study product (i.e. Non-medicinal ingredients: Cellulose, hypromellose, magnesium stearate (vegetal source), ascorbic acid, Colloidal silicon dioxide) * Patients presenting with an active, non-controlled intestinal disease such as Crohn's Disease or ulcerative colitis; * A previous documented C. Difficile infection \< 3 months prior to study initiation ; * Ostomized patients, parenteral nutrition users * Patients with an immunosuppressive therapy or any health condition causing immunosuppression (including haematological malignancies, acquired immune deficiency syndrome (AIDS)) * Ongoing or recent use of antibiotic therapy in the 30 days prior to the study product first administration. * Patients with planned administration of antibiotics other than broad spectrum Penicillin, Cephalosporin or Clindamycin for the treatment of an infection; * Patients with concomitant participation in another clinical trial; * Patients who are not likely to comply with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Assess if Probiotic Prophylaxis (BIO-K+CL1285®) is Effective for the Prevention of AAD in Hospitalized Patients. | Up to 40 days | Incidence of AAD data were collected using questionnaire and diaries given to participants upon discharge. Diagnosis of AAD was made when a patient produced three or more liquid stools in a 24h period after antibiotic treatment with no other obvious reason for diarrhea. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequencies of Other Gastrointestinal Symptoms. | Up to 40 days | Episodes of gastrointestinal disorders during hospitalization were recorded by patient interview and were confirmed by review of patient diaries. |
| Severity of AAD in Hospitalized Patients Ingesting BIO-K+CL1285® or Placebo. | Up to 40 days | Duration of diarrhea was determined by number of continuous days of diarrhea. Average number of liquid stools per day was determined by the sum of the number of liquid stools per day in the AAD episode divided by the duration of diarrhea in days. |
| Frequency of Stool Samples Positive for Clostridium Difficile (C. Difficile) Toxin A and/or B. | Up to 40 days | If diarrhea occured while hospitalized, patients provided a stool sample for C. difficile analysis of Toxin A and/or B. All episodes were recorded by a nurse of clinician on a case report form using the seven-item Bristol Stool Form Scale (Riegler et al., 2001). A diarrhea episode was described as a bowel movement consisting of watery stool with or without solids. |
| Safety Profile of BIO-K+CL1285® Versus Placebo in Hospitalized Patients. | Up to 40 days | Adverse events were reported by patients in the three study groups. |
Participant flow
Recruitment details
1120 patients screened, 255 enrolled at the Xinhua/Yuyao Hospital, Shangai Jiao Tong University, China between Oct. 2008 and March 2009.
Pre-assignment details
Inclusion & exclusion criterias were used to randomized patients.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Two capsules of placebo (devoid of microorganisms) per day. Patients took their daily dose 2h after breakfast and antibiotic administration each day. Patients were then followed for an additionnal 21 days after completion of the assigned intervention. | 84 |
| BIO-K+ CL-1285® & Placebo One capsule of probiotic (BIO-K+ CL-1285® with 50 billion colony forming units (CFU)) and one capsule of placebo (devoid of microorganisms) per day. Patients took their daily dose 2h after breakfast and antibiotic administration each day. Patients were then followed for an additionnal 21 days after completion of the assigned intervention. | 85 |
| BIO-K+ CL-1285 Two capsules of probiotic(BIO-K+ CL-1285® - each capsule contains 50 billion CFU) per day. Patients took their daily dose 2h after breakfast and antibiotic administration each day. Patients were then followed for an additionnal 21 days after completion of the assigned intervention. | 86 |
| Total | 255 |
Baseline characteristics
| Characteristic | Placebo | BIO-K+ CL-1285® & Placebo | BIO-K+ CL-1285 | Total |
|---|---|---|---|---|
| Age Continuous | 60.4 years STANDARD_DEVIATION 5.88 | 60.2 years STANDARD_DEVIATION 6.03 | 60.0 years STANDARD_DEVIATION 6.32 | 60 years STANDARD_DEVIATION 6 |
| Region of Enrollment China | 84 participants | 85 participants | 86 participants | 255 participants |
| Sex: Female, Male Female | 42 Participants | 42 Participants | 40 Participants | 124 Participants |
| Sex: Female, Male Male | 42 Participants | 43 Participants | 46 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 84 | 0 / 85 | 1 / 86 |
| serious Total, serious adverse events | 0 / 84 | 0 / 85 | 0 / 86 |
Outcome results
Primary
To Assess if Probiotic Prophylaxis (BIO-K+CL1285®) is Effective for the Prevention of AAD in Hospitalized Patients.
Incidence of AAD data were collected using questionnaire and diaries given to participants upon discharge. Diagnosis of AAD was made when a patient produced three or more liquid stools in a 24h period after antibiotic treatment with no other obvious reason for diarrhea.
Time frame: Up to 40 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | To Assess if Probiotic Prophylaxis (BIO-K+CL1285®) is Effective for the Prevention of AAD in Hospitalized Patients. | 84 participants |
| BIO-K+ CL-1285® & Placebo | To Assess if Probiotic Prophylaxis (BIO-K+CL1285®) is Effective for the Prevention of AAD in Hospitalized Patients. | 85 participants |
| BIO-K+ CL-1285 | To Assess if Probiotic Prophylaxis (BIO-K+CL1285®) is Effective for the Prevention of AAD in Hospitalized Patients. | 86 participants |
Comparison: The sample size calculation was based on the incidence of AAD. A total of 255 patients was enrolled in order to obtain at least the required 225 evaluable patients.With expected AAD rates of at most 15% - 25% in the treatment groups; and 25% - 35% in the placebo group, these numbers were sufficient to detect the difference in the incidence of AAD between either of the treatment groups vs. placebo with a minimum of 86% statistical power.p-value: =0.02Fisher Exact
Secondary
Frequencies of Other Gastrointestinal Symptoms.
Episodes of gastrointestinal disorders during hospitalization were recorded by patient interview and were confirmed by review of patient diaries.
Time frame: Up to 40 days
Secondary
Frequency of Stool Samples Positive for Clostridium Difficile (C. Difficile) Toxin A and/or B.
If diarrhea occured while hospitalized, patients provided a stool sample for C. difficile analysis of Toxin A and/or B. All episodes were recorded by a nurse of clinician on a case report form using the seven-item Bristol Stool Form Scale (Riegler et al., 2001). A diarrhea episode was described as a bowel movement consisting of watery stool with or without solids.
Time frame: Up to 40 days
Secondary
Safety Profile of BIO-K+CL1285® Versus Placebo in Hospitalized Patients.
Adverse events were reported by patients in the three study groups.
Time frame: Up to 40 days
Secondary
Severity of AAD in Hospitalized Patients Ingesting BIO-K+CL1285® or Placebo.
Duration of diarrhea was determined by number of continuous days of diarrhea. Average number of liquid stools per day was determined by the sum of the number of liquid stools per day in the AAD episode divided by the duration of diarrhea in days.
Time frame: Up to 40 days