Probiotic Lactobacillus Reuteri to Prevent Antibiotic-associated Diarrhea and Clostridium Difficile-related Infections in Hospitalized Children

Phase 3

Completed

• Conditions: Antibiotic Associated Diarrhea; Clostridium Difficile Infection; Gastroenteritis
• Interventions: Dietary Supplement: L reuteri in children on antibiotics

• Registration Number: NCT01295918
• Lead Sponsor: St Marina University Hospital, Varna, Bulgaria

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

Study Timeline

• Study Start: 2011-02
• Study First Submitted: 2011-02-14
• Study First Submitted QC: 2011-02-14
• Study First Posted: 2011-02-15
• Primary Completion: 2013-06
• Status Verified: 2013-09
• Study Completion: 2013-09
• Last Update Submitted: 2013-09-07
• Last Update Posted: 2013-09-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
L. reuteri, Antibiotic, diarrhoea	L reuteri in children on antibiotics	L. reuteri will be ingested by patients on antibiotic therapy, effect of probiotic on AAD will be assessed.

Primary Outcome Measures

Name	Time	Method
To assess if the probiotic L. reuteri is effective in preventing AAD in children	2 years	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

Name	Time	Method
Incidence of mild diarrhea and severity if diarrhea in children with probiotic treatment	2 years	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	2 years	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	2 years	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	2 years	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).

Trial Locations

Locations (2)

Department of Pediatrics at St Marina University Hospital, Varna; 🇧🇬 Varna, Bulgaria

St Marina University Hospital; 🇧🇬 Varna, Bulgaria