Probiotics and Antibiotic Associated Diarrhea in Pediatric Complicated Appendicitis

Study Overview
=================
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.

Official Title
-----------------
Probiotics and Antibiotic Associated Diarrhea in Pediatric Complicated Appendicitis: Prospective Controlled-Comparison Trial

Conditions
-----------------
Appendicitis, Appendicitis; Perforation

Intervention / Treatment
-----------------
* Dietary Supplement: Lactobacillus rhamnosus GG (LGG) Probiotic
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with a post-operative diagnosis of complicated appendicitis who undergo an immediate appendectomy. Patients between the ages of 4 and 18 years of age. Exclusion Criteria: Patients diagnosed with an complicated appendicitis with deferred appendectomy or non-perforated appendicitis Patients that have a history of being immunosuppressed, on immunosuppression therapy, or long-term steroid therapy within the last month. Patients that have central line access. Patients under 4 years of age. Patients that are developmentally delayed and cannot ambulate at baseline. Patients with significant past medical history. Patients that are in Child Protective Services custody. Patients that are incarcerated. Patients that are pregnant. Patients that speak languages other than English and Spanish.

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactobacillus rhanmosus GG(LGG®) Group<br>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. As such, this dietary supplement is not reviewed and approved by the FDA. 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. Patients in the treatment group will receive a standard dose of Lactobacillus rhamnosus GG capsule following their surgery while in the hospital until discharge. | Dietary Supplement: Lactobacillus rhamnosus GG (LGG) Probiotic<br>* 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.<br>* Other names: Culturelle Probiotics Digestive Health;|
| Placebo Comparator: Placebo Control Group<br>Patients in the placebo group will receive a placebo capsule following their surgery while in the hospital until discharge. | Dietary Supplement: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Hospital Stay | Length of hospital stay measured in hours from admission to discharge. | Through study completion, an average 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of diarrhea episodes daily | Documented number of diarrhea episodes each day in EHR. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months | 
| Number of times patient ambulated each day | Documented number of times patient ambulated each day in EHR. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Appendicitis, Probiotics