Amoxicillin for Enteral Nutrition Intolerance in Pediatric Intensive Care Unit

Study Overview
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Brief Summary
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The goal of this randomized controlled study is to investigate the efficacy of enteral amoxicillin for the treatment of children with feeding intolerance in pediatric intensive care unit. Children with feeding intolerance will be randomized into study and comparison groups. The study group will receive amoxicillin 10 mg/kg by nasogastric tube 3 times daily 10 minutes before bolus gastric feeding for 7 days. The comparison group will receive equal volume of distilled water as a placebo. The primary outcome will be the improvement of feeding intolerance on day 7 study timepoint.

Detailed Description
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Malnutrition is a common problem in critically ill children admitted to the pediatric intensive care unit (PICU) with a reported prevalence up to 57%. This condition is associated with increased length of hospital stay, morbidity (e.g., hospital-acquired infections, weakness, and longer duration of mechanical ventilation), and mortality. Data from observational studies indicate that adequate energy intake is associated with better outcomes in the PICU. Enteral nutrition (EN) is the preferred route to administer nutritional support for critically ill children unless contraindicated. However, EN of critically ill children is challenging, and nutritional targets are commonly not attained. EN intolerance (a clinical manifestation of delayed gastric emptying) is one of the main factors for limited delivery of enteral feeding. Promotility agents are commonly used as a first-line treatment for patients with EN intolerance. In critically ill adults, prokinetics have been shown to improve gastric emptying and enhance tolerance to gastric feeding. Available options include metoclopramide, domperidone, and erythromycin. However, there is insufficient evidence for recommending the use of prokinetics in children with critical illness to enhance gastric emptying and EN tolerance. Furthermore, currently available prokinetics are associated with serious side effects. Amoxicillin/clavulanate combination is one of the most commonly prescribed antibiotics for children worldwide. Besides its antibacterial properties, some studies showed that amoxicillin/clavulanate could have prokinetic effects. However, well-designed randomized controlled trials to confirm the prokinetic effects of amoxicillin/clavulanate are lacking. Additionally, no human study has investigated the prokinetic effects of amoxicillin and clavulanate individually. In a study on juvenile rats, amoxicillin alone, but not clavulanate, was shown to increase the amplitude of spontaneous duodenal contractions. The use of amoxicillin alone rather than amoxicillin/clavulanate could have the advantages of avoiding the side effects of clavulanate, lowering the cost, and decreasing the risk of antibiotic resistance. The goal of this randomized controlled study is to investigate the efficacy of enteral amoxicillin for the treatment of children with EN intolerance in PICU.

Official Title
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Efficacy of Amoxicillin for Treatment of Enteral Nutrition Intolerance in Pediatric Intensive Care Unit

Conditions
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Enteral Feeding Intolerance

Intervention / Treatment
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* Drug: Amoxicillin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ranges from 1 month to 12 years. Nasogastric tube feeding Enteral nutrition intolerance after 7 days of admission to the PICU. Exclusion Criteria: Failure to obtain informed consent. Allergy or contraindication to amoxicillin or other beta-lactam antibiotics. Current or recent (within 7 days) treatment with amoxicillin. Ongoing ketogenic diet. Clinical contraindications to advance EN feeds (e.g., bowel obstruction/tight stenosis, severe diarrhea/malabsorption, gut ischemia, severe hypoxemia/acidosis, intractable upper gastrointestinal bleeding, abdominal compartment syndrome, high-output fistula).

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two groups of children with enteral feeding intolerance: Study group: will receive amoxicillin 10 mg/kg (50 mg/ml concentration) by nasogastric tube 3 times daily (8 hours apart) 10 minutes before bolus gastric feeding for 7 days. The nasogastric tube will be flushed by 5 ml distilled water after each dose. Control group: will receive equal volume of distilled water (0.2 ml/kg + 5 ml) as a placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>Children receiving amoxicillin | Drug: Amoxicillin<br>* Amoxicillin 10 mg/kg (50 mg/ml concentration) by nasogastric tube 3 times daily (8 hours apart) 10 minutes before bolus gastric feeding for 7 days.<br>|
| Placebo Comparator: Comparison group<br>Children receiving placebo | Other: Placebo<br>* Distilled water 0.2 ml/kg by nasogastric tube 3 times daily (8 hours apart) 10 minutes before bolus gastric feeding for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feeding tolerance on day 7 | Proportion of participants achieving feeding tolerance (enteral intake ≥ two-thirds of the prescribed daily target in the absence of gastrointestinal symptoms, including large gastric residual volume (≥ 50% of enteral feeding in the last 4 hours), vomiting (≥ 2 times gastric content in 24 hours period), diarrhea (≥ 4 times loose stool with negative fluid balance in 24 hours period), abdominal distention (≥ 2 cm increase in abdominal girth), abdominal pain, melena, or hematochezia) on day 7 study timepoint | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enteral intake ≥ two-thirds of the prescribed daily target on day 7 | Proportion of participants achieving enteral intake ≥ two-thirds of the prescribed daily target on day 7 study timepoint | 7 days | 
| Change in achieved percentage of prescribed enteral feeding on day 7 study compared with baseline | Change in achieved percentage of prescribed enteral feeding on day 7 study timepoint compared with baseline | 7 days | 
| Large gastric residual volume on day 7 | Proportion of participants with large gastric residual volume (≥ 50% of enteral feeding in the last 4 hours) on day 7 study timepoint | 7 days | 
| Vomiting on day 7 | Proportion of participants with vomiting (≥ 2 times gastric content in 24 hours period) on day 7 study timepoint | 7 days | 
| Diarrhea | Proportion of participants with diarrhea (≥ 4 times loose stool with negative fluid balance in 24 hours period) | 7 days | 
| Abdominal distention | Proportion of participants with abdominal distention (≥ 2 cm increase in abdominal girth) | 7 days | 
| Melena/hematochezia | Proportion of participants with melena/hematochezia | 7 days | 
| Skin rash | Proportion of participants with skin rash | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Feeding intolerance, Pediatric intensive care unit, PICU, Amoxicillin