Amoxicillin for Enteral Nutrition Intolerance in Pediatric Intensive Care Unit

NCT ID: NCT05828758

Last Updated: 2023-04-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-24

Study Completion Date

2024-05-10

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.

Conditions

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Enteral Feeding Intolerance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Enrolled children will be equally randomized into study and control group using computer generated numbers, which will be sealed into sequentially numbered opaque envelopes by a person not belonging to the research team. For each enrolled participant, the envelope in order will be opened, and the assigned study drug will be used. A pharmacist will fill the active and placebo preparations in similar containers with sealed code for identification. Participants' families, treating clinicians, and investigators will be unaware of group assignment and drug/placebo therapy.

Study Groups

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Study group

Children receiving amoxicillin

Group Type EXPERIMENTAL

Amoxicillin

Intervention Type DRUG

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.

Comparison group

Children receiving placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type OTHER

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).
Minimum Eligible Age

1 Month

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sohag University

OTHER

Sponsor Role lead

Responsible Party

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Abanob Amgad Francis

Pediatric Resident

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Safaa H Ali, MD, PhD

Role: STUDY_CHAIR

Sohag University

Locations

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Pediatric Intensive Care Unit - Sohag University Hospital

Sohag, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Abanob Francis, MBBCh

Role: CONTACT

0201094930123

Elsayed Abdelkreem, MD, PhD

Role: CONTACT

+201114232126

Facility Contacts

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Abdelrahim A Sadek, MD, PhD

Role: primary

+201065067057

References

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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.

Reference Type BACKGROUND
PMID: 26218259 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32981755 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32077997 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28691958 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35884015 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28061320 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30962102 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33428672 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33215023 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22584747 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1929247 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25844706 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19682776 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23863821 (View on PubMed)

Abdelatif RG, Francis AA, Abdelkreem E, Ahmed SH. Amoxicillin for critically ill children with enteral nutrition intolerance (AmoxENI study): A randomized controlled trial. J Pediatr Gastroenterol Nutr. 2025 Sep;81(3):712-721. doi: 10.1002/jpn3.70105. Epub 2025 Jun 12.

Reference Type DERIVED
PMID: 40501446 (View on PubMed)

Other Identifiers

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Soh-Med-23-04-16MS

Identifier Type: -

Identifier Source: org_study_id

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