Clinical trial NCT04529980: Probiotics and Antibiotic Associated Diarrhea in Pediatric Complicated Appendicitis
Official title: Probiotics and Antibiotic Associated Diarrhea in Pediatric Complicated Appendicitis: Prospective Controlled-Comparison Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Appendicitis
Appendicitis; Perforation
Keywords: Appendicitis
Probiotics
Lead sponsor: Children's Health
Sponsor class: OTHER
First posted: 2020-08-28
Enrollment: 98
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Those randomized to the treatment group will be given probiotic therapy until discharge, while those randomized to the placebo group will be given a placebo until discharge.
Primary purpose: TREATMENT

Brief summary: To determine the effectiveness of the use of probiotics in patients with a diagnosis of complicated appendicitis on antibiotic associated diarrhea (AAD). Probiotics are defined as live microbial organisms that when administered in sufficient amounts, can provide a protective benefit to the individual patient. The use of probiotics in a pediatric population exposed to antibiotics and gastrointestinal surgery such as an appendectomy may provide a protective effect and prevent antibiotic associated diarrhea (ADD)

Detailed description: Appendicitis is the most common urgent surgical procedure performed on children. Approximately one third of the population end up having complicated appendicitis with evidence of peritoneal contamination and infection or abscess requiring the use of IV antibiotics and prolonged hospital stay. Antibiotic Associated Diarrhea (AAD) is a common complication seen in both outpatient and inpatient settings in approximately a third of all patients treated with antibiotics (Mantegazza, et al., 2018). In particular, pediatric patients experience ADD 11-62% of the time and can up upwards to 80% in hospitalized toddlers (Mantegazza, et al., 2018). Current literature defines AAD as three or more liquid stools per day. The causes of AAD are often related to the use of multiple antibiotics, prolonged hospital stay and gastrointestinal surgery. Antibiotics often disturb the normal enteric microbiome in the gut and allow for an increased growth of pathogens (Hojsak, 2017). AAD can occur as late as six to eight weeks after antibiotic exposure. Lactobacillus rhanmosus GG(LGG®)(Culturelle) is an over the counter dietary supplement that can help to restore the balance in the gut by promoting colonization to support better digestion and immune health.This study does not intend to investigate route of administration, dose, patient population, or other factor that significantly increases the risk (or decreases the acceptability of the risk) associated with the use of the dietary supplement.At Children's Medical Center, the investigators see over 1000 cases of appendicitis a year with approximately 1/3 of those patients being complicated appendicitis. For those requiring immediate appendectomy, the typical course of treatment include surgery, admission to the hospital for 3 to 5 days, administration of IV antibiotics while in hospital, and discharge orders for oral antibiotics to complete their treatment. The investigators propose to perform a randomized controlled trial where one group of patients will receive probiotic therapy and another group of patients does not. The investigators hypothesize patients given probiotics after a diagnosis of complicated appendicitis with immediate appendectomy who receive antibiotic treatment during their inpatient stay will decrease the overall length of stay (LOS) by 25% vs the LOS in those patients who do not receive probiotics.

Eligibility criteria: Inclusion Criteria:

1. Patients with a post-operative diagnosis of complicated appendicitis who undergo an immediate appendectomy.
2. Patients between the ages of 4 and 18 years of age.

Exclusion Criteria:

1. Patients diagnosed with an complicated appendicitis with deferred appendectomy or non-perforated appendicitis
2. Patients that have a history of being immunosuppressed, on immunosuppression therapy, or long-term steroid therapy within the last month.
3. Patients that have central line access.
4. Patients under 4 years of age.
5. Patients that are developmentally delayed and cannot ambulate at baseline.
6. Patients with significant past medical history.
7. Patients that are in Child Protective Services custody.
8. Patients that are incarcerated.
9. Patients that are pregnant.
10. Patients that speak languages other than English and Spanish.

Primary outcomes:
measure: Length of Hospital Stay
timeFrame: From admission to discharge, up to 1 month
Secondary outcomes:
measure: Number of Diarrhea Episodes Daily
timeFrame: up to 1 month
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Children's Health Children's Medical Center
state: Texas
Study officials:
affiliation: Children's Health
name: Mayra Garcia, APRN, CNS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Agamennone V, Krul CAM, Rijkers G, Kort R. A practical guide for probiotics applied to the case of antibiotic-associated diarrhea in The Netherlands. BMC Gastroenterol. 2018 Aug 6;18(1):103. doi: 10.1186/s12876-018-0831-x.
citation: Bethel M. Probiotics for the prevention of pediatric antibiotic-associated diarrhea: Summary of a Cochrane review. Explore (NY). 2019 Sep-Oct;15(5):382-383. doi: 10.1016/j.explore.2019.07.001. Epub 2019 Jul 11. No abstract available.
citation: Hayes SR, Vargas AJ. Probiotics for the Prevention of Pediatric Antibiotic-Associated Diarrhea. Explore (NY). 2016 Nov-Dec;12(6):463-466. doi: 10.1016/j.explore.2016.08.015. Epub 2016 Aug 26.
citation: Hojsak I. Probiotics in Children: What Is the Evidence? Pediatr Gastroenterol Hepatol Nutr. 2017 Sep;20(3):139-146. doi: 10.5223/pghn.2017.20.3.139. Epub 2017 Sep 26.
citation: Mantegazza C, Molinari P, D'Auria E, Sonnino M, Morelli L, Zuccotti GV. Probiotics and antibiotic-associated diarrhea in children: A review and new evidence on Lactobacillus rhamnosus GG during and after antibiotic treatment. Pharmacol Res. 2018 Feb;128:63-72. doi: 10.1016/j.phrs.2017.08.001. Epub 2017 Aug 19.
citation: Szajewska H, Kolodziej M. Systematic review with meta-analysis: Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea in children and adults. Aliment Pharmacol Ther. 2015 Nov;42(10):1149-57. doi: 10.1111/apt.13404. Epub 2015 Sep 13.