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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Miglena Georgieva, St Marina University Hospital, Varna, Bulgaria
ClinicalTrials.gov Identifier:
NCT01295918
First received: February 14, 2011
Last updated: September 7, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Antibiotic Associated Diarrhea
Clostridium Difficile Infection
Gastroenteritis
Dietary Supplement: L reuteri in children on antibiotics
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy of the Probiotic Lactobacillus Reuteri in Prevention of Antibiotic-associated Diarrhea and Clostridium Difficile-related Infections in Hospitalized Children and Adolescents

Resource links provided by NLM:


Further study details as provided by St Marina University Hospital, Varna, Bulgaria:

Primary Outcome Measures:
  • To assess if the probiotic L. reuteri is effective in preventing AAD in children [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 100
Study Start Date: February 2011
Study Completion Date: September 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Placebo, antibiotic, diarrhea
Placebo Comparator: L. reuteri, Antibiotic, diarrhoea
L. reuteri will be ingested by patients on antibiotic therapy, effect of probiotic on AAD will be assessed.
Dietary Supplement: L reuteri in children on antibiotics
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.

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

  Eligibility

Ages Eligible for Study:   3 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01295918

Locations
Bulgaria
Department of Pediatrics at St Marina University Hospital, Varna
Varna, Bulgaria, 9010
St Marina University Hospital
Varna, Bulgaria, 9002
Sponsors and Collaborators
St Marina University Hospital, Varna, Bulgaria
Investigators
Principal Investigator: Miglena I Georgieva, PhD Pediatric gastroenterology ward
  More Information

No publications provided

Responsible Party: Miglena Georgieva, Assoc Prof Miglena Georgieva, MD, PhD, St Marina University Hospital, Varna, Bulgaria., St Marina University Hospital, Varna, Bulgaria
ClinicalTrials.gov Identifier: NCT01295918     History of Changes
Other Study ID Numbers: 128/13.01.2011
Study First Received: February 14, 2011
Last Updated: September 7, 2013
Health Authority: Bulgaria: Ethics committee at St Marina University Hospital, Varna

Keywords provided by St Marina University Hospital, Varna, Bulgaria:
probiotic
AAD
Lactobacillus reuteri
diarrhea

Additional relevant MeSH terms:
Diarrhea
Gastroenteritis
Clostridium Infections
Signs and Symptoms, Digestive
Signs and Symptoms
Gastrointestinal Diseases
Digestive System Diseases
Gram-Positive Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents

ClinicalTrials.gov processed this record on July 26, 2014