Emergency Department Probiotic Treatment of Pediatric Gastroenteritis

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

886 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2017-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The objective of this study is to determine for previously healthy children who present to a Canadian Emergency Department (ED) with acute gastroenteritis (infection or irritation of the digestive tract); if compared with placebo, the administration of a probiotic agent (Lacidofil) will result in a significantly lower proportion of children developing moderate to severe disease over the subsequent 2 weeks and will not be associated with a significantly greater occurrence of side effects.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Impact of Emergency Department Probiotic Treatment of Diarrheal Illness on Daycare Attendance

NCT00760773

Gastroenteritis

TERMINATED PHASE2

Efficacy of Two Probiotic Preparations in Children With Acute Diarrhoea

NCT02080130

Gastroenteritis

WITHDRAWN NA

Efficacy and Safety of Probiotics in the Treatment of Acute Gastroenteritis in Children

NCT03539913

Acute Gastroenteritis

COMPLETED PHASE4

Impact of Emergency Department Probiotic (LGG) Treatment of Pediatric Gastroenteritis

NCT01773967

Gastroenteritis

COMPLETED PHASE2/PHASE3

Probiotics in the Management of Acute Rotavirus Diarrhea in Bolivian Children

NCT00981877

Diarrhea Rotavirus Infection

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The burden of acute gastroenteritis (AGE) on children and their families continues to be enormous. It accounts for 1.7 million pediatric emergency department (ED) visits annually in the United States and nearly 240,000 in Canada. Children often suffer from prolonged and severe illness; amongst hospitalized Canadian children, 19% have clinical sepsis, 7% seizures and 4% require intensive care unit admission.3 In a study that we conducted at 11 Canadian EDs, 51% of children experienced moderate to severe disease. Parents rate such episodes as being equivalent to a 10 day admission (moderate) and persistent moderate hearing loss (severe). The burden is augmented by the 50% household transmission rate2, 6 and 42% prolonged work absenteeism rate. Apart from supportive care, health-care providers have little to offer to relieve suffering.

Probiotics, which are defined as viable microbial preparations that have a beneficial effect on the health of the host, represent a rapidly expanding field. While they are available as over-the-counter products, according to the National Institutes of Health, the Food and Drug Administration has not yet approved a single agent for any health claims. Further, a 2012 meta-analysis concluded that there is limited data to support their indications and no published pediatric gastroenteritis trials reported on side effects. Thus, understanding the benefits and side effects of probiotics is crucial before widespread use can be endorsed. Although probiotic clinical trials have been performed, only one (still unpublished) has been ED based. Most studies to date have been significantly flawed and guidelines do NOT endorse their use stating that well-controlled human trials are needed. Consequently, we and others have found that they are rarely used in clinical practice. Reasons cited include (1) questionable clinical meaning to the outcomes evaluated thus far; (2) absence of studies in the appropriate patient population, and (3) a lack of confidence in the quality of probiotic agents studied.

This study will address (1) the needs of the medical community, which is aware of the widening gap between the number of important pediatric and adult trials and (2) the interest of caregivers in "probiotics" - 71% are aware of the term; 31% believe they may be beneficial in children with diarrhea, and \> 90% would administer a probiotic if it could make their child better. Furthermore, our pilot study has provided promising preliminary data and has proven the feasibility of our methods. Thus we are poised to conduct a randomized controlled trial (RCT)that will definitively determine if meaningful benefits are derived from probiotic use and will provide critical information regarding their mechanism of action. This information will impact on practice, the burden of disease, and ensure that children receive the best care possible. The results of our proposed RCT will enable guidelines to either clearly endorse or recommend against the routine use of a probiotic agent in children with Acute Gastroenteritis.

We also hypothesize that the therapeutic benefits of probiotics in children with AGE vary by infecting pathogen. We have assembled a team to bridge the gap between the clinical RCT team, molecular diagnostics, and immunologic to quantify the pathogen-specific effects of probiotics. The latter is likely because there are distinct mechanisms (e.g. invasive, inflammatory, non-inflammatory) by which pathogens cause clinical symptoms. Similarly, probiotic effects are exerted through multiple modes-of-action (e.g. direct antimicrobial activity, competitive exclusion, immune response stimulation, inhibition of virulence gene or protein expression). The simultaneous evaluation of pathogen-specific effects on clinical, microbiological and immunological levels has not previously been performed.

The knowledge gained through this multi-faceted approach will inform understanding of the probiotic-host-pathogen interactions that are responsible for improved clinical outcomes in children with AGE. Our study population, outpatient children, is both the main group of patients who suffer from AGE as well as the main consumer of probiotics. Thus, our findings will be relevant and ready for translation into clinical care while simultaneously opening up avenues for future research.

The principal questions to be addressed are as follows:

Hypotheses: In children aged 3-48 months presenting to an ED with less than 72 hours of AGE like symptoms, compared with placebo, the administration of a probiotic agent:

1. Will result in a significantly lower proportion of children developing moderate to severe disease over the subsequent 2 weeks.
2. Will not be associated with a significantly greater occurrence of minor side effects.
3. Will be associated with a greater increase in secretory IgA (sIgA).
4. Will have varying effects based on the etiologic pathogen, given the diverse underlying pathophysiologic processes induced by the causative agents and the multiple mechanisms of action of probiotics.

Clinical Efficacy:

Primary Question: For previously healthy children, ages 3-48 months, who present to an ED with less than 72 hours of AGE like symptoms, is the proportion who develop moderate to severe disease \[Modified Vesikari Score (MVS) ≥ 9\] following ED evaluation, significantly different in those who receive a probiotic agent (Lacidofil) compared to those who receive placebo?

Secondary Questions: In this group of patients, amongst those receiving active treatment versus placebo:

1. Is there a difference in the (a) duration of diarrhea or (b) duration of vomiting?
2. Is there a difference in the proportion who require an unscheduled health care provider visit?
3. Is there a difference in the effectiveness of treatment based on the infecting pathogen?

Side Effect Profile:

Question: In this group of patients, is the proportion that experiences a side effect (e.g. bloating, fever, abdominal distention, rash) significantly different in those who receive Lacidofil compared to placebo?

Mechanism of Action:

Question: In this group of patients, are fecal sIgA levels 5 days and 4 weeks after the initiation of treatment higher in those who receive Lacidofil compared to those who receive placebo?

Microbiologic - Stool Pathogen-Specific Load:

Question: In this group of patients, is there a difference in the pathogen specific reduction in stool pathogen load in those who receive Lacidofil compared to those who receive placebo?

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Gastroenteritis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Lacidofil

Lacidofil sachet containing active ingredients

Group Type EXPERIMENTAL

Lacidofil

Intervention Type DRUG

All patients in this arm of the study will take 1 sachet twice daily for 5 days. Each sachet will contain a minimum of 4 billion colony-forming units (CFU) of Lactobacillus rhamnosus Rosell-11 (95%) and L. helveticus Rosell-52 (5%). The total weight of all ingredients is 1 gm. Doses should be ideally separated by 12 hours (minimum of 8 hours) and taken within 30 minutes of food/drink. If the child vomits within 15 minutes of medication administration (initial or subsequent dose), the dose will be repeated. Total daily dose = 8 billion CFU x 5 days.

Placebo

Placebo sachet containing inactive ingredients

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

All patients in this arm of the study will take 1 sachet containing inactive ingredients (maltodextrin, magnesium stearate, and ascorbic acid) twice daily for 5 days. Doses should be ideally separated by 12 hours (minimum of 8 hours) and taken within 30 minutes of food/drink. If the child vomits within 15 minutes of medication administration (initial or subsequent dose), the dose will be repeated. Total of 2 sachets per day for 5 days.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Placebo

All patients in this arm of the study will take 1 sachet containing inactive ingredients (maltodextrin, magnesium stearate, and ascorbic acid) twice daily for 5 days. Doses should be ideally separated by 12 hours (minimum of 8 hours) and taken within 30 minutes of food/drink. If the child vomits within 15 minutes of medication administration (initial or subsequent dose), the dose will be repeated. Total of 2 sachets per day for 5 days.

Intervention Type DRUG

Lacidofil

All patients in this arm of the study will take 1 sachet twice daily for 5 days. Each sachet will contain a minimum of 4 billion colony-forming units (CFU) of Lactobacillus rhamnosus Rosell-11 (95%) and L. helveticus Rosell-52 (5%). The total weight of all ingredients is 1 gm. Doses should be ideally separated by 12 hours (minimum of 8 hours) and taken within 30 minutes of food/drink. If the child vomits within 15 minutes of medication administration (initial or subsequent dose), the dose will be repeated. Total daily dose = 8 billion CFU x 5 days.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Presence of diarrhea: defined as ≥ 3 watery stools in a 24-hour period
* Duration of vomiting and/or diarrhea \< 72 hours
* Age 3 to \< 48 months

Exclusion Criteria

* Presence of an indwelling vascular access line or structural heart disease
* Taking immunosuppressive therapy, or known history of immunodeficiency
* Hematochezia in the preceding 72 hours, underlying significant chronic gastrointestinal problem or inflammatory bowel disease
* Family member with an indwelling vascular access line, on immunosuppressive therapy, or with a known immunodeficiency
* Bilious vomiting
* Probiotic use (supplement) in the preceding 2 weeks
* Previously enrolled in this trial
* Daily follow-up not possible
* Allergy to Soy
* Pre-existing (known) pancreatic dysfunction or insufficiency
* Oral or Gastrointestinal surgery within preceding 7 days

Minimum Eligible Age

3 Months

Maximum Eligible Age

48 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Dr. Stephen Freedman

Associate Professor of Pediatrics; Alberta Children's Hospital Foundation Professor in Child Health and Wellness Alberta Children's Hospital Theme Lead

Responsibility Role SPONSOR_INVESTIGATOR