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

• ClinicalTrials.gov Identifier: NCT01773967
• Recruitment Status: Completed
• First Posted: January 23, 2013
• Results First Posted: September 6, 2019
• Last Update Posted: September 6, 2019
• Sponsor: Washington University School of Medicine
• Collaborators: 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
• Information provided by (Responsible Party): Washington University School of Medicine

Tracking Information

• First Submitted Date: January 10, 2013
• First Posted Date: January 23, 2013
• Results First Submitted Date: June 25, 2019
• Results First Posted Date: September 6, 2019
• Last Update Posted Date: September 6, 2019
• Actual Study Start Date: July 2014
• Actual Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 13, 2019)

Number of Participants With Modified Vesikari Scale Score >=9 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: January 18, 2013)

• Modified Vesikari Score [ Time Frame: 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
• Severe adverse events [ Time Frame: 1 year ]
  presence of severe adverse events up to 1 year after treatment

Current Secondary Outcome Measures (submitted: August 13, 2019)

• Number of Participants With LGG Bacteremia [ Time Frame: 1 month ]
  bacteremia caused by LGG
• Diarrhea Duration [ Time Frame: 14 days ]
  diarrhea duration in hours after randomization

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Impact of Emergency Department Probiotic (LGG) Treatment of Pediatric Gastroenteritis
• Official Title: Impact of Emergency Department Probiotic (LGG) Treatment of Pediatric Gastroenteritis
• Brief Summary: The investigators will study the efficacy and side effect profile of LGG, a probiotic, in pediatric patients with acute gastroenteritis.
• Detailed Description: Multicenter randomized controlled trial of LGG in patients 3-48 months of age presenting to the Emergency Department with acute gastroenteritis.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Gastroenteritis

Intervention

• Drug: LGG
  LGG 10^10 cfu PO BID X 5 days
  Other Names:

  • Lactobacillus GG ATCC 53103
  • Lactobacillus rhamnosus
  • culturelle
• Drug: micro-crystalline cellulose
  1 capsule PO bid x 5 days
  Other Name: placebo micro-crystalline cellulose

Study Arms

• Experimental: LGG
  LGG 10^10 cfu PO bid x 5 days
  Intervention: Drug: LGG
• Placebo Comparator: Placebo
  micro-crystalline cellulose PO bid x 5 days
  Intervention: Drug: micro-crystalline cellulose

Publications *

• Freedman SB, Finkelstein Y, Pang XL, Chui L, Tarr PI, VanBuren JM, Olsen C, Lee BE, Hall-Moore CA, Sapien R, O'Connell K, Levine AC, Poonai N, Roskind C, Schuh S, Rogers A, Bhatt S, Gouin S, Mahajan P, Vance C, Hurley K, Powell EC, Farion KJ, Schnadower D. Pathogen-Specific Effects of Probiotics in Children With Acute Gastroenteritis Seeking Emergency Care: A Randomized Trial. Clin Infect Dis. 2022 Aug 24;75(1):55-64. doi: 10.1093/cid/ciab876.
• Schnadower D, O'Connell KJ, VanBuren JM, Vance C, Tarr PI, Schuh S, Hurley K, Rogers AJ, Poonai N, Roskind CG, Bhatt SR, Gouin S, Mahajan P, Olsen CS, Powell EC, Farion K, Sapien RE, Chun TH, Freedman SB; Pediatric Emergency Care Applied Research Network and Pediatric Emergency Research Canada. Association Between Diarrhea Duration and Severity and Probiotic Efficacy in Children With Acute Gastroenteritis. Am J Gastroenterol. 2021 Jul 1;116(7):1523-1532. doi: 10.14309/ajg.0000000000001295.
• Freedman SB, Roskind CG, Schuh S, VanBuren JM, Norris JG, Tarr PI, Hurley K, Levine AC, Rogers A, Bhatt S, Gouin S, Mahajan P, Vance C, Powell EC, Farion KJ, Sapien R, O'Connell K, Poonai N, Schnadower D; Pediatric Emergency Research Canada and Pediatric Emergency Care Applied Research Networks. Comparing Pediatric Gastroenteritis Emergency Department Care in Canada and the United States. Pediatrics. 2021 Jun;147(6):e2020030890. doi: 10.1542/peds.2020-030890. Epub 2021 May 20.
• Poonai N, Powell EC, Schnadower D, Casper TC, Roskind CG, Olsen CS, Tarr PI, Mahajan P, Rogers AJ, Schuh S, Hurley KF, Gouin S, Vance C, Farion KJ, Sapien RE, O'Connell KJ, Levine AC, Bhatt S, Freedman SB; Pediatric Emergency Care Applied Research Network (PECARN) and Pediatric Emergency Research Canada (PERC). Variables Associated With Intravenous Rehydration and Hospitalization in Children With Acute Gastroenteritis: A Secondary Analysis of 2 Randomized Clinical Trials. JAMA Netw Open. 2021 Apr 1;4(4):e216433. doi: 10.1001/jamanetworkopen.2021.6433. Erratum In: JAMA Netw Open. 2021 Jun 1;4(6):e2116800.
• Schnadower D, Sapien RE, Casper TC, Vance C, Tarr PI, O'Connell KJ, Levine AC, Roskind CG, Rogers AJ, Bhatt SR, Mahajan P, Powell EC, Olsen CS, Gorelick MH, Dean JM, Freedman SB; Pediatric Emergency Care Applied Research Network (PECARN) Probiotics Study. Association between Age, Weight, and Dose and Clinical Response to Probiotics in Children with Acute Gastroenteritis. J Nutr. 2021 Jan 4;151(1):65-72. doi: 10.1093/jn/nxaa313.
• Schnadower D, Tarr PI, Casper TC, Gorelick MH, Dean JM, O'Connell KJ, Mahajan P, Levine AC, Bhatt SR, Roskind CG, Powell EC, Rogers AJ, Vance C, Sapien RE, Olsen CS, Metheney M, Dickey VP, Hall-Moore C, Freedman SB. Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children. N Engl J Med. 2018 Nov 22;379(21):2002-2014. doi: 10.1056/NEJMoa1802598.
• Schnadower D, Tarr PI, Casper TC, Gorelick MH, Dean MJ, O'Connell KJ, Mahajan P, Chun TH, Bhatt SR, Roskind CG, Powell EC, Rogers AJ, Vance C, Sapien RE, Gao F, Freedman SB. Randomised controlled trial of Lactobacillus rhamnosus (LGG) versus placebo in children presenting to the emergency department with acute gastroenteritis: the PECARN probiotic study protocol. BMJ Open. 2017 Sep 24;7(9):e018115. doi: 10.1136/bmjopen-2017-018115.
• Freedman SB, Williamson-Urquhart S, Schuh S, Sherman PM, Farion KJ, Gouin S, Willan AR, Goeree R, Johnson DW, Black K, Schnadower D, Gorelick MH; Pediatric Emergency Research Canada (PERC) Gastroenteritis Study Group. Impact of emergency department probiotic treatment of pediatric gastroenteritis: study protocol for the PROGUT (Probiotic Regimen for Outpatient Gastroenteritis Utility of Treatment) randomized controlled trial. Trials. 2014 May 14;15:170. doi: 10.1186/1745-6215-15-170.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 13, 2019): 971
• Original Estimated Enrollment (submitted: January 18, 2013): 900
• Actual Study Completion Date: August 2018
• Actual Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Months to 48 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01773967
• Other Study ID Numbers: 1R01HD071915( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Washington University School of Medicine
• Original Responsible Party: David Schnadower, Washington University School of Medicine, Assistant Professor of Pediatrics
• Current Study Sponsor: Washington University School of Medicine
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: Washington University School of Medicine
• Verification Date: August 2019