Acute DiarrheaPAIDNCT02817165
Probiotics for the Prevention of Antibiotic-Associated Diarrhea
A study testing Probiotic (BioK+) in people with Acute Diarrhea, run by The Hospital for Sick Children at 2 sites in Canada.
Trial summary
In North America, one of the most common reasons for hospitalization in previously healthy children is for the treatment of infections with antibiotics. This study will determine if, in previously healthy children hospitalized and prescribed intravenous (IV) antibiotics, the co-administration of a probiotic milk… Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- Conditions the study is for
- Acute Diarrhea
- What is being tested?
- Probiotic (BioK+)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 2 sitesCanada
- Study dates
- Nov 2016to Jan 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Participants will be children aged 1 year to 17 years admitted to the General Pediatric inpatient unit at The Hospital for Sick Children (Site 1) or McMaster Children's Hospital (Site 2).
- Participants will be prescribed IV antibiotics with a planned duration of 1 or more days, and a total course of both IV and oral antibiotics, if applicable, of no more than 28 days.
- Parent (if parent-report) or patient (if patient-report) is able to communicate in English (read, write, speak).
Who cannot join
- Parental or patient (e.g. child > 12 years old) report of current diarrhea, diarrhea within the last week.
- Lactose intolerance.
- Allergies to strawberry, dried citrus pulp, or any other components of the study product.
- Immuno-compromised patients or those on immunosuppressive agents (e.g. heart or kidney transplant, complex care, sickle cell disease, chemotherapy agents, oral prednisone).
- Patients with known or potentially compromised gut integrity (e.g. short gut, Inflammatory Bowel Disease, Celiac disease, Irritable Bowel Syndrome, nasogastric, nasojejunal or gastrostomy tube).
- Children with serious and/or unstable medical conditions (e.g. diabetes, cardiovascular, renal, lung, psychiatric illness, bleeding disorders, etc.).
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- Children admitted to a medical or surgical subspecialty unit.
- Patients enrolled in another study.
- Patients previously randomized to this study.
- Patient is pregnant.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
McMaster Children's Hospital
Hamilton, Ontario, L8N 3Z5
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Official title: Probiotics in the Prevention of Antibiotic-Associated Diarrhea in Hospitalized Children: a Randomized Trial
In North America, one of the most common reasons for hospitalization in previously healthy children is for the treatment of infections with antibiotics. This study will determine if, in previously healthy children hospitalized and prescribed intravenous (IV) antibiotics, the co-administration of a probiotic milk product containing good bacteria, is safe and effective for reducing AAD, as compared to a placebo (identical appearing milk product). This will be a two-center, randomized, masked, placebo-controlled clinical trial. The results of this study will help inform clinicians and families on the use of probiotics in the prevention of AAD, a common side effect of antibiotic use among hospitalized children.
Read the detailed description
A two-centred randomized, multi-blind (i.e. patients, caregivers, data collectors, outcome assessors, data managers and analysts), placebo-controlled clinical trial intended to evaluate the efficacy and safety of Bio-K+ (Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2) in the prevention of AAD in hospitalized children 1 year to 17 years of age administered IV antibiotics.
- Conditions
- Acute Diarrhea
- Being tested
- Probiotic (BioK+), Placebo
- Keywords
- Probiotics, diarrhea, antibiotic, children, hospital
- Medical subject headings
- Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic (BioK+)Dietary supplement
Probiotic (BioK+) with 3 stains of Lactobacillus
PlaceboOther
Strawberry flavored tub of milk, identical (taste, color, odor) to the active Bio-K+ treatment.
| Study group | Role | What they receive |
|---|---|---|
| Probiotic (BioK+) | Experimental | Children will receive 10-40 billion CFUs/day of Bio-K+ (Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2), with dose based on their weight. The product will be administered as a strawberry flavored tub of milk. Receives: Dietary Supplement: Probiotic (BioK+) |
| Placebo | Placebo comparator | Strawberry flavored tub of milk, identical (taste, color, odor) to the active Bio-K+ treatment. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of antibiotic-associated diarrhea (AAD)
The investigators will employ a questionnaire addressing Pediatric Acute Diarrhea (qPAD), a measure of diarrhea involving the assessment of stool frequency and consistency for each bowel movement. To measure consistency, the qPAD contains a stool consistency classification system. Our registered sample size is based on pilot data from The Hospital for Sick Children indicating that the incidence of AAD is 33% (95% CI 23% to 43%) according to the qPAD. Given an estimated baseline AAD risk of 32.9% and a 48% relative risk reduction in AAD (Johnston et al, Cochrane Library, 2011), a randomized trial with 80% power and a 2-sided alpha of 0.05 comparing Bio-K+ with placebo would require a total sample size of 118 patients per group (236 total).
Measured: 2 weeks after antibiotic + probiotic completion
Incidence of antibiotic-associated diarrhea (AAD), global impression
Given that parents have knowledge of the child's typical bowel movements per day, the investigators will also employ a Global Rating Scale for diarrhea (GRSd), using a 0 to 4 scale (0 = no diarrhea, 1 = mild diarrhea, 2 = moderate diarrhea, 3 = severe diarrhea, 4 = worse imaginable diarrhea). The investigators will ask participants to select values based on diarrhea severity, which is a combination of stool frequency and consistency over 24 hours. Our registered sample size is based on the incidence of AAD (33%; 95% CI 23% to 43%) according to the qPAD. However, the incidence of AAD according to GRSd is 23%, which corresponds to the lower bound of the 95% CI for the qPAD. The investigators are currently applying for additional peer-reviewed funds. If these funds are obtained the investigators will power the trial based GRSd, a more conservative AAD incidence (23%). The investigators will also power the trial for a smaller treatment effect (39% relative risk reduction).
Measured: 2 weeks after antibiotic + probiotic completion
Secondary outcomes (3)
Severity of AAD
The investigators will assess severity using the qPAD and the investigators will employ definitions for diarrhea from the Canadian Nosocomial Infection Surveillance Program, modified for use in children, defined as: severe: ≥6 loose/unformed/liquid stools; moderate: ≥3 loose/unformed/liquid stools; mild: a change in stooling pattern to 1-2 loose/unformed/liquid stools daily (Gravel 2007). The investigators will classify severity according to the 24-hour period with the highest degree of severity.
Measured: 2 weeks after antibiotic completion
Adverse events
Incidence of mild (e.g. self-resolving), moderate (e.g. those that warrant medical evaluation) and serious (e.g. those that warrant continued hospitalization) adverse events based on criteria adopted by the National Institute of Health common terminology criteria for adverse events (NIH severity) will be evaluated.
Measured: 2 weeks after antibiotic completion
Duration of AAD
The investigators will measure duration of AAD using a definition of diarrhea resolution (diarrhea offset) developed based on a systematic review of 138 trials of Pediatric Acute Diarrhea, and Delphi consensus with a panel of experts in pediatrics, clinical gastroenterology and measurement (Johnston BC et al. Pediatrics 2010; Jul;126(1):e222-31; Johnston BC et al. Symposium Probio, Quebec City, Canada, 2015).
For children up to 17 years of age, acute diarrhea typically lasts less than 7 days and not longer than 14 days and resolution is marked by
- production of 2 consecutive normal stools (i.e. "soft and formed" or "hard and formed") stool or;
- production of one normal stool followed by 12 hours with no stool production or;
- normal stool production (or no stool production) for a period of 24 hours.
Measured: 2 weeks after antibiotic completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2016 (estimated)
- Study startNov 2016
- Primary completionOct 2017
- Study completionJan 2018
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute DiarrheaStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- McMaster University
- Responsible party
- Principal investigator, Patricia Parkin, The Hospital for Sick Children
- Investigators
- Patricia Parkin, MD, Principal investigator, The Hospital for Sick ChildrenGordon Guyatt, MD, Study chair, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02817165
- Sponsor's protocol ID
- 1000052303
- Acronym
- PAID
- Status last verified
- Apr 2018
- First submitted
- 12 Apr 2016
- Last updated
- 18 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: To be determined.
Publications
Johnston BC, Shamseer L, da Costa BR, Tsuyuki RT, Vohra S. Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review. Pediatrics. 2010 Jul;126(1):e222-31. doi: 10.1542/peds.2009-3667. Epub 2010 Jun 21.
PubMed 20566617Johnston B, Pirrello D, Lytvyn L, Mahant S, Sherman P, Ship N, Parkin P. Prospective cohort study of antibiotic-associated diarrhea among hospitalized children. Symposium Probio, Quebec City, Canada. (October 29, 2015).
Goldenberg JZ, Lytvyn L, Steurich J, Parkin P, Mahant S, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2015 Dec 22;(12):CD004827. doi: 10.1002/14651858.CD004827.pub4.
PubMed 26695080
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Probiotics in the Prevention of Antibiotic-Associated Diarrhea in Hospitalized Children: a Randomized Trial
- ClinicalTrials.gov ID
- NCT02817165
- Acronym / sponsor ID
- PAID / 1000052303
- Conditions
- Acute Diarrhea
- Keywords
- Probiotics, diarrhea, antibiotic, children, hospital
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 16 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- McMaster University
- Study start
- Nov 2016
- Primary completion
- Oct 2017 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 29 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In North America, one of the most common reasons for hospitalization in previously healthy children is for the treatment of infections with antibiotics. This study will determine if, in previously healthy children hospitalized and prescribed intravenous (IV) antibiotics, the co-administration of a probiotic milk product containing good bacteria, is safe and effective for reducing AAD, as compared to a placebo (identical appearing milk product). This will be a two-center, randomized, masked, placebo-controlled clinical trial. The results of this study will help inform clinicians and families on the use of probiotics in the prevention of AAD, a common side effect of antibiotic use among hospitalized children.
Detailed description
A two-centred randomized, multi-blind (i.e. patients, caregivers, data collectors, outcome assessors, data managers and analysts), placebo-controlled clinical trial intended to evaluate the efficacy and safety of Bio-K+ (Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2) in the prevention of AAD in hospitalized children 1 year to 17 years of age administered IV antibiotics.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic (BioK+) | Experimental | Dietary Supplement: Probiotic (BioK+)Children will receive 10-40 billion CFUs/day of Bio-K+ (Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2), with dose based on their weight. The product will be administered as a strawberry flavored tub of milk. |
| Placebo | Placebo comparator | Other: PlaceboStrawberry flavored tub of milk, identical (taste, color, odor) to the active Bio-K+ treatment. |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Participants will be children aged 1 year to 17 years admitted to the General Pediatric inpatient unit at The Hospital for Sick Children (Site 1) or McMaster Children's Hospital (Site 2).
- Participants will be prescribed IV antibiotics with a planned duration of 1 or more days, and a total course of both IV and oral antibiotics, if applicable, of no more than 28 days.
- Parent (if parent-report) or patient (if patient-report) is able to communicate in English (read, write, speak).
Key exclusion criteria (10 listed)
- Parental or patient (e.g. child > 12 years old) report of current diarrhea, diarrhea within the last week.
- Lactose intolerance.
- Allergies to strawberry, dried citrus pulp, or any other components of the study product.
- Immuno-compromised patients or those on immunosuppressive agents (e.g. heart or kidney transplant, complex care, sickle cell disease, chemotherapy agents, oral prednisone).
- Patients with known or potentially compromised gut integrity (e.g. short gut, Inflammatory Bowel Disease, Celiac disease, Irritable Bowel Syndrome, nasogastric, nasojejunal or gastrostomy tube).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotic (BioK+)Probiotic (BioK+) with 3 stains of Lactobacillus | Dietary supplement | Probiotic (BioK+) |
| PlaceboStrawberry flavored tub of milk, identical (taste, color, odor) to the active Bio-K+ treatment. | Other | Placebo |
Primary outcome
Incidence of antibiotic-associated diarrhea (AAD)
Time frame: 2 weeks after antibiotic + probiotic completion
The investigators will employ a questionnaire addressing Pediatric Acute Diarrhea (qPAD), a measure of diarrhea involving the assessment of stool frequency and consistency for each bowel movement. To measure consistency, the qPAD contains a stool consistency classification system. Our registered sample size is based on pilot data from The Hospital for Sick Children indicating that the incidence of AAD is 33% (95% CI 23% to 43%) according to the qPAD. Given an estimated baseline AAD risk of 32.9% and a 48% relative risk reduction in AAD (Johnston et al, Cochrane Library, 2011), a randomized trial with 80% power and a 2-sided alpha of 0.05 comparing Bio-K+ with placebo would require a total sample size of 118 patients per group (236 total).
Incidence of antibiotic-associated diarrhea (AAD), global impression
Time frame: 2 weeks after antibiotic + probiotic completion
Given that parents have knowledge of the child's typical bowel movements per day, the investigators will also employ a Global Rating Scale for diarrhea (GRSd), using a 0 to 4 scale (0 = no diarrhea, 1 = mild diarrhea, 2 = moderate diarrhea, 3 = severe diarrhea, 4 = worse imaginable diarrhea). The investigators will ask participants to select values based on diarrhea severity, which is a combination of stool frequency and consistency over 24 hours. Our registered sample size is based on the incidence of AAD (33%; 95% CI 23% to 43%) according to the qPAD. However, the incidence of AAD according to GRSd is 23%, which corresponds to the lower bound of the 95% CI for the qPAD. The investigators are currently applying for additional peer-reviewed funds. If these funds are obtained the investigators will power the trial based GRSd, a more conservative AAD incidence (23%). The investigators will also power the trial for a smaller treatment effect (39% relative risk reduction).
3 secondary outcomes
Severity of AAD
Time frame: 2 weeks after antibiotic completion
Adverse events
Time frame: 2 weeks after antibiotic completion
Duration of AAD
Time frame: 2 weeks after antibiotic completion
Results and safety
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2018.
- Background: PubMed 20566617Johnston BC, Shamseer L, da Costa BR, Tsuyuki RT, Vohra S. Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review. Pediatrics. 2010 Jul;126(1):e222-31. doi: 10.1542/peds.2009-3667. Epub 2010 Jun 21.
- BackgroundJohnston B, Pirrello D, Lytvyn L, Mahant S, Sherman P, Ship N, Parkin P. Prospective cohort study of antibiotic-associated diarrhea among hospitalized children. Symposium Probio, Quebec City, Canada. (October 29, 2015).
- Background: PubMed 26695080Goldenberg JZ, Lytvyn L, Steurich J, Parkin P, Mahant S, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2015 Dec 22;(12):CD004827. doi: 10.1002/14651858.CD004827.pub4.
- Individual participant dataSharing planned: Undecided. To be determined.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patricia Parkin, MD principal investigator
The Hospital for Sick Children
Gordon Guyatt, MD study chair
McMaster University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic (BioK+) in people with Acute Diarrhea, run by The Hospital for Sick Children at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of antibiotic-associated diarrhea (AAD) (time frame: 2 weeks after antibiotic + probiotic completion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02817165, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2018.