Amoxicillin for Enteral Nutrition Intolerance in Pediatric Intensive Care Unit

Enteral Feeding Intolerance Clinical Trial

— AmoxENI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05828758
• Other study ID #: Soh-Med-23-04-16MS
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: April 24, 2023
• Est. completion date: May 10, 2024

Study information

• Verified date: April 2023
• Source: Sohag University
• Contact: Abanob Francis, MBBCh
• Phone: 0201094930123
• Email: abanobamgad[@]med.sohag.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: May 10, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 12 Years

Eligibility

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).

Related Conditions & MeSH terms

• Enteral Feeding Intolerance

Intervention

Drug:
• Amoxicillin
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.

Other:
• Placebo
Distilled water 0.2 ml/kg by nasogastric tube 3 times daily (8 hours apart) 10 minutes before bolus gastric feeding for 7 days.

Locations

Country	Name	City	State
Egypt	Pediatric Intensive Care Unit - Sohag University Hospital	Sohag

Sponsors (1)

Lead Sponsor	Collaborator
Sohag University

Country where clinical trial is conducted

Egypt, 

References & Publications (14)

Caron F, Ducrotte P, Lerebours E, Colin R, Humbert G, Denis P. Effects of amoxicillin-clavulanate combination on the motility of the small intestine in human beings. Antimicrob Agents Chemother. 1991 Jun;35(6):1085-8. doi: 10.1128/AAC.35.6.1085. — View Citation

Chiusolo F, Capriati T, Erba I, Bianchi R, Ciofi Degli Atti ML, Picardo S, Diamanti A. Management of Enteral Nutrition in the Pediatric Intensive Care Unit: Prokinetic Effects of Amoxicillin/Clavulanate in Real Life Conditions. Pediatr Gastroenterol Hepatol Nutr. 2020 Nov;23(6):521-530. doi: 10.5223/pghn.2020.23.6.521. Epub 2020 Nov 5. — View Citation

Ciciora SL, Williams KC, Gariepy CE. Effects of Amoxicillin and Clavulanic Acid on the Spontaneous Mechanical Activity of Juvenile Rat Duodenum. J Pediatr Gastroenterol Nutr. 2015 Sep;61(3):340-5. doi: 10.1097/MPG.0000000000000804. — View Citation

Eveleens RD, Hulst JM, de Koning BAE, van Brakel J, Rizopoulos D, Garcia Guerra G, Vanhorebeek I, Van den Berghe G, Joosten KFM, Verbruggen SCAT. Achieving enteral nutrition during the acute phase in critically ill children: Associations with patient characteristics and clinical outcome. Clin Nutr. 2021 Apr;40(4):1911-1919. doi: 10.1016/j.clnu.2020.09.005. Epub 2020 Sep 16. — View Citation

Eveleens RD, Joosten KFM, de Koning BAE, Hulst JM, Verbruggen SCAT. Definitions, predictors and outcomes of feeding intolerance in critically ill children: A systematic review. Clin Nutr. 2020 Mar;39(3):685-693. doi: 10.1016/j.clnu.2019.03.026. Epub 2019 Mar 30. — View Citation

Gomez R, Fernandez S, Aspirot A, Punati J, Skaggs B, Mousa H, Di Lorenzo C. Effect of amoxicillin/clavulanate on gastrointestinal motility in children. J Pediatr Gastroenterol Nutr. 2012 Jun;54(6):780-4. doi: 10.1097/MPG.0b013e31824204e4. — View Citation

Hulst JM, Zwart H, Hop WC, Joosten KF. Dutch national survey to test the STRONGkids nutritional risk screening tool in hospitalized children. Clin Nutr. 2010 Feb;29(1):106-11. doi: 10.1016/j.clnu.2009.07.006. Epub 2009 Aug 13. — View Citation

Kratochvil M, Klucka J, Klabusayova E, Musilova T, Vafek V, Skrisovska T, Djakow J, Havrankova P, Osinova D, Stourac P. Nutrition in Pediatric Intensive Care: A Narrative Review. Children (Basel). 2022 Jul 11;9(7):1031. doi: 10.3390/children9071031. — View Citation

Martinez EE, Douglas K, Nurko S, Mehta NM. Gastric Dysmotility in Critically Ill Children: Pathophysiology, Diagnosis, and Management. Pediatr Crit Care Med. 2015 Nov;16(9):828-36. doi: 10.1097/PCC.0000000000000493. — View Citation

Martinez EE, Pereira LM, Gura K, Stenquist N, Ariagno K, Nurko S, Mehta NM. Gastric Emptying in Critically Ill Children. JPEN J Parenter Enteral Nutr. 2017 Sep;41(7):1100-1109. doi: 10.1177/0148607116686330. Epub 2017 Jan 6. — View Citation

Mehta NM, Skillman HE, Irving SY, Coss-Bu JA, Vermilyea S, Farrington EA, McKeever L, Hall AM, Goday PS, Braunschweig C. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Pediatric Critically Ill Patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. Pediatr Crit Care Med. 2017 Jul;18(7):675-715. doi: 10.1097/PCC.0000000000001134. — View Citation

Peng R, Li H, Yang L, Zeng L, Yi Q, Xu P, Pan X, Zhang L. The efficacy and safety of prokinetics in critically ill adults receiving gastric feeding tubes: A systematic review and meta-analysis. PLoS One. 2021 Jan 11;16(1):e0245317. doi: 10.1371/journal.pone.0245317. eCollection 2021. — View Citation

Straney L, Clements A, Parslow RC, Pearson G, Shann F, Alexander J, Slater A; ANZICS Paediatric Study Group and the Paediatric Intensive Care Audit Network. Paediatric index of mortality 3: an updated model for predicting mortality in pediatric intensive care*. Pediatr Crit Care Med. 2013 Sep;14(7):673-81. doi: 10.1097/PCC.0b013e31829760cf. — View Citation

Tume LN, Valla FV, Joosten K, Jotterand Chaparro C, Latten L, Marino LV, Macleod I, Moullet C, Pathan N, Rooze S, van Rosmalen J, Verbruggen SCAT. Nutritional support for children during critical illness: European Society of Pediatric and Neonatal Intensive Care (ESPNIC) metabolism, endocrine and nutrition section position statement and clinical recommendations. Intensive Care Med. 2020 Mar;46(3):411-425. doi: 10.1007/s00134-019-05922-5. Epub 2020 Feb 20. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Vomiting on day 7	Proportion of participants with vomiting (= 2 times gastric content in 24 hours period) on day 7 study timepoint	7 days
Secondary	Diarrhea	Proportion of participants with diarrhea (= 4 times loose stool with negative fluid balance in 24 hours period)	7 days
Secondary	Abdominal distention	Proportion of participants with abdominal distention (= 2 cm increase in abdominal girth)	7 days
Secondary	Melena/hematochezia	Proportion of participants with melena/hematochezia	7 days
Secondary	Skin rash	Proportion of participants with skin rash	7 days