Efficacy and Safety Study in the Prevention of Antibiotic-Associated Diarrhea (AAD) and Clostridium Difficile-Associated Diarrhea (CDAD) in Hospitalized Adult Patients Exposed to Nosocomial Infection

A Double-blind, Randomized, Placebo-controlled, Single-center Study of the Efficacy and Safety of BIO-K+ CL-1285® in the Prevention of Antibiotic-Associated Diarrhea (AAD) and Clostridium Difficile-Associated Diarrhea (CDAD) in Hospitalized Adult Patients Exposed to Nosocomial Infection

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.

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile-Associated Diarrhea; Antibiotic-Associated Diarrhea
• Intervention / Treatment: Other: Placebo; Other: BIO-K+ CL-1285®

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Other: Placebo; Placebo is devoid of microorganisms.
Active Comparator: BIO-K+ CL-1285; Two probiotic capsules (BIO-K+ CL-1285®) 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.	Other: BIO-K+ CL-1285®; A mixture of Lactobacillus acidophilus and Lactobacillus casei, contains over 50 billion living bacteria per administered dose.
Other: BIO-K+ CL-1285® & placebo; One probiotic capsule (BIO-K+ CL-1285®) and one placebo capsule (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.	Other: Placebo; Placebo is devoid of microorganisms.; Other: BIO-K+ CL-1285®; A mixture of Lactobacillus acidophilus and Lactobacillus casei, contains over 50 billion living bacteria per administered dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 40 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 40 days
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.	Up to 40 days
Safety Profile of BIO-K+CL1285® Versus Placebo in Hospitalized Patients.	Adverse events were reported by patients in the three study groups.	Up to 40 days
Frequencies of Other Gastrointestinal Symptoms.	Episodes of gastrointestinal disorders during hospitalization were recorded by patient interview and were confirmed by review of patient diaries.	Up to 40 days

Collaborators and Investigators

• Sponsor: Bio-K Plus International Inc.
• Collaborators: Sprim Advanced Life Sciences
• Investigators: Principal Investigator: Gao XingWang, MD, Xinhua/Yuyao Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Publications and helpful links

General Publications

• Gao XW, Mubasher M, Fang CY, Reifer C, Miller LE. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol. 2010 Jul;105(7):1636-41. doi: 10.1038/ajg.2010.11. Epub 2010 Feb 9.

Helpful Links

• Dose-response probiotic study for AAD and CDAD

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: August 12, 2009
• First Submitted That Met QC Criteria: August 12, 2009
• First Posted (Estimate): August 13, 2009

Study Record Updates

• Last Update Posted (Estimate): March 13, 2012
• Last Update Submitted That Met QC Criteria: March 9, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Probiotic; Antibiotic-Associated Diarrhea (AAD) Prevention; Clostridium Difficile-Associated Diarrhea (CDAD)Prevention
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Disease Attributes; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Iatrogenic Disease; Diarrhea; Clostridium Infections; Cross Infection
• Other Study ID Numbers: 07-SC-9-BIK-01; CL 1285-AAD-CH01