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

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01773967
• Collaborator: Columbia University (Other), Northwestern University (Other), University of New Mexico (Other), Children's National Research Institute (Other), University of Utah (Other), Wayne State University (Other), Children's Hospital Medical Center, Cincinnati (Other), University of Michigan (Other), Brown University (Other), University of California, Davis (Other)
• Enrollment: 971
• Locations: 10
• Arms: 2
• Actual Duration (Months): 49
• Patients Per Site: 97.1
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The investigators will study the efficacy and side effect profile of LGG, a probiotic, in pediatric patients with acute gastroenteritis.

Condition or Disease	Intervention/Treatment	Phase
Gastroenteritis	Drug: LGG; Drug: micro-crystalline cellulose	Phase 2/Phase 3

Detailed Description

Multicenter randomized controlled trial of LGG in patients 3-48 months of age presenting to the Emergency Department with acute gastroenteritis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 971 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Impact of Emergency Department Probiotic (LGG) Treatment of Pediatric Gastroenteritis
• Actual Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Aug 1, 2018
• Actual Study Completion Date: Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LGG LGG 10^10 cfu PO bid x 5 days	Drug: LGG; LGG 10^10 cfu PO BID X 5 days; Other Names: Lactobacillus GG ATCC 53103 Lactobacillus rhamnosus culturelle
Placebo Comparator: Placebo micro-crystalline cellulose PO bid x 5 days	Drug: micro-crystalline cellulose; 1 capsule PO bid x 5 days; Other Names: placebo micro-crystalline cellulose

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Modified Vesikari Scale Score >=9 [14 days]

   This is a validated gastroenteritis severity score that includes duration and frequency of diarrhea, duration and frequency of vomiting, duration and frequency of fever and use of health care resources. Scores >=9 indicate moderate-severe gastroenteritis. Higher is worse.

Secondary Outcome Measures

1. Number of Participants With LGG Bacteremia [1 month]

   bacteremia caused by LGG

2. Diarrhea Duration [14 days]

   diarrhea duration in hours after randomization

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Months to 48 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age 3-48 months (have not yet reached their fourth birthday); AND

2. Presence of 3 or more watery stools within 24 hours of screening; AND

3. Duration of vomiting or diarrhea less than 7 days; AND

4. Symptoms consistent with acute intestinal infectious process.

Exclusion Criteria:

1. Presence of an indwelling vascular access line; OR

2. Presence of structural heart disease excluding non-pathological heart murmurs; OR

3. Receiving immunosuppressive therapy or history of immunodeficiency; OR

4. Hematochezia in the preceding 48 hours; OR

5. Chronic gastrointestinal problems (e.g. short gut syndrome, inflammatory bowel disease); OR

6. Patients with known pancreatitis; OR

7. History of abdominal surgery; OR

8. Critically ill patients; OR

9. Family member with an indwelling vascular access line, or on immunosuppressive therapy, or with a known immunodeficiency; OR

10. Bilious emesis; OR

11. Probiotic use (supplement) in the preceding 2 weeks; OR

12. Oral or intravenous steroid use in the preceding six months; OR

13. Previously enrolled in this trial; OR

14. Allergy to lactobacillus or Microcrystalline Cellulose (MCC); OR

15. Allergy to erythromycin, clindamycin, AND betalactam antibiotics (all); OR

16. Not available for daily follow-up while symptomatic; OR

17. Parent/guardian not speaking English or Spanish; OR

18. Under 6 months old AND premature (<37 weeks).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Davis Medical Center	Sacramento	California	United States	95817
2	Children's National Medical Center	Washington	District of Columbia	United States	20010
3	Lurie Children's Hospital	Chicago	Illinois	United States	60611
4	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
5	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
6	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
7	University of New Mexico	Albuquerque	New Mexico	United States	87106
8	Children's Hospital of New York	New York	New York	United States	10032
9	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
10	Hasbro Children's Hospital	Providence	Rhode Island	United States	02903

Sponsors and Collaborators

• Washington University School of Medicine
• Columbia University
• Northwestern University
• University of New Mexico
• Children's National Research Institute
• University of Utah
• Wayne State University
• Children's Hospital Medical Center, Cincinnati
• University of Michigan
• Brown University
• University of California, Davis

Investigators

• Principal Investigator: Kimberly Quayle, MD, Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 6, 2017

More Information

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01773967
• Other Study ID Numbers: 1R01HD071915; NCT00970164
• First Posted: Jan 23, 2013
• Last Update Posted: Sep 6, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Washington University School of Medicine: Lactobacillus rhamnosus GG; LGG; Probiotic; Gastroenteritis; acute gastroenteritis; child; pediatric; RCT
• Additional relevant MeSH terms: Gastroenteritis; Emergencies

Study Results

Participant Flow

Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo
Arm/Group Description	LGG 10^10 cfu PO bid x 5 days LGG: LGG 10^10 cfu PO BID X 5 days	micro-crystalline cellulose PO bid x 5 days micro-crystalline cellulose: 1 capsule PO bid x 5 days
Period Title: Overall Study
STARTED	483	488
COMPLETED	468	475
NOT COMPLETED	15	13

Baseline Characteristics

Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo	Total
Arm/Group Description	LGG 10^10 cfu PO bid x 5 days LGG: LGG 10^10 cfu PO BID X 5 days	micro-crystalline cellulose PO bid x 5 days micro-crystalline cellulose: 1 capsule PO bid x 5 days	Total of all reporting groups
Overall Participants	483	488	971
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	1.4	1.4	1.4
Sex: Female, Male (Count of Participants)
Female	236 48.9%	222 45.5%	458 47.2%
Male	247 51.1%	266 54.5%	513 52.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	9 1.9%	0 0%	9 0.9%
Asian	8 1.7%	6 1.2%	14 1.4%
Native Hawaiian or Other Pacific Islander	1 0.2%	3 0.6%	4 0.4%
Black or African American	176 36.4%	162 33.2%	338 34.8%
White	144 29.8%	163 33.4%	307 31.6%
More than one race	24 5%	16 3.3%	40 4.1%
Unknown or Not Reported	121 25.1%	138 28.3%	259 26.7%
Region of Enrollment (participants) [Number]
United States	483 100%	488 100%	971 100%
Median Modified Vesikari Scale score at presentation (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	12	12	12

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Modified Vesikari Scale Score >=9
Description	This is a validated gastroenteritis severity score that includes duration and frequency of diarrhea, duration and frequency of vomiting, duration and frequency of fever and use of health care resources. Scores >=9 indicate moderate-severe gastroenteritis. Higher is worse.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo
Arm/Group Description	LGG 10^10 cfu PO bid x 5 days LGG: LGG 10^10 cfu PO BID X 5 days	micro-crystalline cellulose PO bid x 5 days micro-crystalline cellulose: 1 capsule PO bid x 5 days
Measure Participants	468	475
Count of Participants [Participants]	55 11.4%	60 12.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lactobacillus Rhamnosus GG, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Mantel Haenszel
	Comments

2. Secondary Outcome

Title	Number of Participants With LGG Bacteremia
Description	bacteremia caused by LGG
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo
Arm/Group Description	LGG 10^10 cfu PO bid x 5 days LGG: LGG 10^10 cfu PO BID X 5 days	micro-crystalline cellulose PO bid x 5 days micro-crystalline cellulose: 1 capsule PO bid x 5 days
Measure Participants	468	475
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Diarrhea Duration
Description	diarrhea duration in hours after randomization
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo
Arm/Group Description	LGG 10^10 cfu PO bid x 5 days LGG: LGG 10^10 cfu PO BID X 5 days	micro-crystalline cellulose PO bid x 5 days micro-crystalline cellulose: 1 capsule PO bid x 5 days
Measure Participants	468	475
Median (Inter-Quartile Range) [hours]	49.7	50.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lactobacillus Rhamnosus GG, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Van Elteren's modification Mann-Whitney
	Comments

Adverse Events

Time Frame	35 days, long term follow up 1 year
Arm/Group Title	Lactobacillus Rhamnosus GG		Placebo
Arm/Group Description	LGG 10^10 cfu PO bid x 5 days LGG: LGG 10^10 cfu PO BID X 5 days		micro-crystalline cellulose PO bid x 5 days micro-crystalline cellulose: 1 capsule PO bid x 5 days
All Cause Mortality
	Lactobacillus Rhamnosus GG		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/483 (0%)		0/488 (0%)
Serious Adverse Events
	Lactobacillus Rhamnosus GG		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/483 (1.7%)		13/488 (2.7%)
Gastrointestinal disorders
Worsening diarrhea	3/483 (0.6%)	3	4/488 (0.8%)	4
ileus	1/483 (0.2%)	1	1/488 (0.2%)	1
dehydration	1/483 (0.2%)	1	2/488 (0.4%)	2
vomiting	0/483 (0%)	0	1/488 (0.2%)	1
General disorders
fever	0/483 (0%)	0	1/488 (0.2%)	1
Metabolism and nutrition disorders
metabolic acidosis	1/483 (0.2%)	1	0/488 (0%)	0
Nervous system disorders
seizure	1/483 (0.2%)	1	1/488 (0.2%)	1
lethargy	1/483 (0.2%)	1	1/488 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
lower respiratory infection	0/483 (0%)	0	2/488 (0.4%)	2
Other (Not Including Serious) Adverse Events
	Lactobacillus Rhamnosus GG		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/483 (11.4%)		49/488 (10%)
Gastrointestinal disorders
other	40/483 (8.3%)	40	35/488 (7.2%)	35
Respiratory, thoracic and mediastinal disorders
other	15/483 (3.1%)	15	14/488 (2.9%)	14

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.