Probiotic Lactobacillus Reuteri to Prevent Antibiotic-associated Diarrhea and Clostridium Difficile-related Infections in Hospitalized Children (AADreuter)
Primary Purpose
Antibiotic Associated Diarrhea, Clostridium Difficile Infection, Gastroenteritis
Status
Completed
Phase
Phase 3
Locations
Bulgaria
Study Type
Interventional
Intervention
L reuteri in children on antibiotics
Sponsored by
About this trial
This is an interventional prevention trial for Antibiotic Associated Diarrhea focused on measuring probiotic, AAD, Lactobacillus reuteri, diarrhea
Eligibility Criteria
Inclusion Criteria:
- 3 - 18 years of age
- Receiving antibiotics for not more than 48 hours prior to enrolment and free from diarrhoea
- The signed informed consent by one/both parents / legal guardian and by the subject if she/he is 12 years or older
- Available throughout the study period
- No use of any other probiotic products during the study period (Bulgarian yoghurt without added probiotics can be used)
- Subject or parents/guardian should have the mental ability to understand and willingness to fulfil all the details of the protocol
Exclusion Criteria:
- Three or more soft and unformed or watery stools per day at admission
- Receiving chemotherapy or radiation therapy
- Diagnosis of inflammatory bowel disease
- Enteral or parenteral nutrition only
- Requiring care in an intensive care unit
- Status post-bowel resection during hospitalization
- Receiving antibiotics four weeks prior to hospitalization
- Patient with severe life threatening illness or immunocompromised (HIV/AIDS, cancer, genetic disorders including cystic fibrosis, children with opportunistic infections, metabolic diseases)
- Pregnancy
- Lack of possibility to store the study product in a temperature below 25°C during the hot season of the year
Sites / Locations
- St Marina University Hospital
- Department of Pediatrics at St Marina University Hospital, Varna
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Placebo Comparator
Arm Label
Placebo, antibiotic, diarrhea
L. reuteri, Antibiotic, diarrhoea
Arm Description
L. reuteri will be ingested by patients on antibiotic therapy, effect of probiotic on AAD will be assessed.
Outcomes
Primary Outcome Measures
To assess if the probiotic L. reuteri is effective in preventing AAD in children
Incidence of diarrhea during and after treatment with antibiotics in patients ingesting L. reuteri versus placebo during the study period, measured as mean number of episodes per patient. An episode of diarrhea is defined as three or more (≥ 3) soft and unformed or watery bowel movements per day for at least 48 hours.
Secondary Outcome Measures
Incidence of mild diarrhea and severity if diarrhea in children with probiotic treatment
Incidence of mild diarrhoea during and after treatment with antibiotics in patients ingesting L. reuteri versus placebo during the study period is measured as mean number of episodes per patient. An episode of mild diarrhoea is defined as any soft and unformed or watery bowel movements not fulfilling the definition of AAD.
Severity of diarrhoea in patients ingesting L. reuteri versus placebo
Severity of diarrhoea in patients ingesting L. reuteri versus placebo is measured as the total number of soft and unformed or watery bowel movements during an episode of diarrhoea and the presence of blood and mucus in faeces.
Frequency of stool samples positive for C. difficile toxin A and B
Frequency of stool samples positive for C. difficile toxin A and B at baseline, when presenting with diarrhoea during the study period, and at the follow-up 21 days post-antibiotic treatment is done to detect possible clearance of C. difficile, in patients ingesting L. reuteri versus placebo.
Frequencies of other gastrointestinal symptoms
Frequencies of other gastrointestinal symptoms during antibiotic use and 7 and 21 days after cessation of antibiotic use, in the L. reuteri group versus placebo is to be assessed by the validated GSRS score (Gastrointestinal Symptom Rating Score, Svedlund et al., 1988).
Full Information
NCT ID
NCT01295918
First Posted
February 14, 2011
Last Updated
September 7, 2013
Sponsor
St Marina University Hospital, Varna, Bulgaria
1. Study Identification
Unique Protocol Identification Number
NCT01295918
Brief Title
Probiotic Lactobacillus Reuteri to Prevent Antibiotic-associated Diarrhea and Clostridium Difficile-related Infections in Hospitalized Children
Acronym
AADreuter
Official Title
Efficacy of the Probiotic Lactobacillus Reuteri in Prevention of Antibiotic-associated Diarrhea and Clostridium Difficile-related Infections in Hospitalized Children and Adolescents
Study Type
Interventional
2. Study Status
Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St Marina University Hospital, Varna, Bulgaria
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine if the daily intake of the probiotic Lactobacillus reuteri prevents antibiotic-associated diarrhoea and related Clostridium difficile infections in children and adolescents.
Detailed Description
Antibiotic-associated diarrhoea (AAD) occurs in up to 25% of all individuals receiving antibiotics (Bartlett, 2002). In hospitalized patients, AAD is related to significant increases in mortality, length of stay, and cost of medical care (McFarland, 2006). Twenty-nine percent of hospitalized patients may develop diarrhoea after antibiotic use; therefore, identifying strategies to minimize antibiotic-associated diarrhoea could be of significant medical and economic advantage (McFarland, 1998). A promising tool in this area is the probiotic Lactobacillus reuteri
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Antibiotic Associated Diarrhea, Clostridium Difficile Infection, Gastroenteritis
Keywords
probiotic, AAD, Lactobacillus reuteri, diarrhea
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo, antibiotic, diarrhea
Arm Type
No Intervention
Arm Title
L. reuteri, Antibiotic, diarrhoea
Arm Type
Placebo Comparator
Arm Description
L. reuteri will be ingested by patients on antibiotic therapy, effect of probiotic on AAD will be assessed.
Intervention Type
Dietary Supplement
Intervention Name(s)
L reuteri in children on antibiotics
Intervention Description
Each patient will be assigned to receive either a probiotic supplement containing 1 x 10 8 CFU Lactobacillus reuteri DSM 17938 in the form of one chewable tablet once per day (BioGaia AB, Stockholm, Sweden) or placebo, identical in taste and appearance. The probiotic or placebo will be taken 2 hours after lunch each day, during the entire period of antibiotic treatment and for an additional 7 days.
Primary Outcome Measure Information:
Title
To assess if the probiotic L. reuteri is effective in preventing AAD in children
Description
Incidence of diarrhea during and after treatment with antibiotics in patients ingesting L. reuteri versus placebo during the study period, measured as mean number of episodes per patient. An episode of diarrhea is defined as three or more (≥ 3) soft and unformed or watery bowel movements per day for at least 48 hours.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Incidence of mild diarrhea and severity if diarrhea in children with probiotic treatment
Description
Incidence of mild diarrhoea during and after treatment with antibiotics in patients ingesting L. reuteri versus placebo during the study period is measured as mean number of episodes per patient. An episode of mild diarrhoea is defined as any soft and unformed or watery bowel movements not fulfilling the definition of AAD.
Time Frame
2 years
Title
Severity of diarrhoea in patients ingesting L. reuteri versus placebo
Description
Severity of diarrhoea in patients ingesting L. reuteri versus placebo is measured as the total number of soft and unformed or watery bowel movements during an episode of diarrhoea and the presence of blood and mucus in faeces.
Time Frame
2 years
Title
Frequency of stool samples positive for C. difficile toxin A and B
Description
Frequency of stool samples positive for C. difficile toxin A and B at baseline, when presenting with diarrhoea during the study period, and at the follow-up 21 days post-antibiotic treatment is done to detect possible clearance of C. difficile, in patients ingesting L. reuteri versus placebo.
Time Frame
2 years
Title
Frequencies of other gastrointestinal symptoms
Description
Frequencies of other gastrointestinal symptoms during antibiotic use and 7 and 21 days after cessation of antibiotic use, in the L. reuteri group versus placebo is to be assessed by the validated GSRS score (Gastrointestinal Symptom Rating Score, Svedlund et al., 1988).
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
3 - 18 years of age
Receiving antibiotics for not more than 48 hours prior to enrolment and free from diarrhoea
The signed informed consent by one/both parents / legal guardian and by the subject if she/he is 12 years or older
Available throughout the study period
No use of any other probiotic products during the study period (Bulgarian yoghurt without added probiotics can be used)
Subject or parents/guardian should have the mental ability to understand and willingness to fulfil all the details of the protocol
Exclusion Criteria:
Three or more soft and unformed or watery stools per day at admission
Receiving chemotherapy or radiation therapy
Diagnosis of inflammatory bowel disease
Enteral or parenteral nutrition only
Requiring care in an intensive care unit
Status post-bowel resection during hospitalization
Receiving antibiotics four weeks prior to hospitalization
Patient with severe life threatening illness or immunocompromised (HIV/AIDS, cancer, genetic disorders including cystic fibrosis, children with opportunistic infections, metabolic diseases)
Pregnancy
Lack of possibility to store the study product in a temperature below 25°C during the hot season of the year
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miglena I Georgieva, PhD
Organizational Affiliation
Pediatric gastroenterology ward
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Marina University Hospital
City
Varna
ZIP/Postal Code
9002
Country
Bulgaria
Facility Name
Department of Pediatrics at St Marina University Hospital, Varna
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
12. IPD Sharing Statement
Learn more about this trial
Probiotic Lactobacillus Reuteri to Prevent Antibiotic-associated Diarrhea and Clostridium Difficile-related Infections in Hospitalized Children
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