A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients

NCT07484633 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2024-518115-19-02
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to examine the success and safety of administering certain antibiotics (beta-lactams) given in a longer 3-hour infusion to children (0-17 years) who are critically ill and have severe infection. The main question it aims to answer is: Is the longer infusion more effective than the conventional short-term (0.5-hour-long) infusion? Researchers will compare the 3-hour-long infusion group to the 0.5-hour-long infusion group to determine whether the longer infusion can cure the infection earlier and whether it is equally safe. The doses are the same in the two groups. Only the duration differs until the patient receives the antibiotic. Participants will:

• be given the required antibiotic drug in a 3-hour-long or in a 0.5 hour-long infusion.
• be examined to make sure their blood drug levels are correct. This will require two blood tests.
• be treated according to routine care and have examinations and blood tests performed.

Conditions

Infection; Sepsis; NICU; PICU; Beta Lactams

Outcome Measures

Primary Outcomes (1)

• Proportion of patients achieving PK/PD index: 100% fT>MIC (Ctrough >MIC)

  In critically ill patients, it is recommended to maintain plasma levels 1-4 times higher than the minimal inhibitory concentration (MIC) of the bacterium isolated throughout the dosing interval (100% fT\>1-4×MIC). The primary outcome for the study will be the proportion of patients achieving therapeutic and optimal drug exposure, defined as plasma concentrations above the MIC for 100% of the dosing interval. Trough plasma concentration levels should be measured. The pharmacokinetic-pharmacodynamic (PK/PD) index used is 100% fT\>MIC (Ctrough \>MIC).

  two times >48 hours after initiation of antibiotic treatment according to the treatment allocation

Secondary Outcomes (13)

• Proportion of patients achieving PK/PD index: 100% fT>4xMIC (Ctrough >4xMIC)

  two times >48 hours after initiation of antibiotic treatment according to the treatment allocation

• Time to normalisation of C-reactive protein (CRP)

  From enrollment to the end of treatment (maximum 30 days).

• Time to normalisation of procalcitonin (PCT)

  From enrollment to the end of treatment (maximum 30 days).

• Time to normalisation of white blood cells (WBC)

  From enrollment to the end of treatment (maximum 30 days).

• Microbiological eradication rate

  On day 0 before initiation of antibiotic treatment and on days 2, 3 and 5 after initiation of antibiotic treatment

Study Arms (2)

pediatric patients, short-term infusion (P, SI) and neonatal patients, short-term infusion (N, SI)

ACTIVE COMPARATOR

subset P: 28 days - 17 years subset N: term or pre-term infants \< 28 days of post-natal age, or PMA\* \< 44 weeks \*postmenstrual age

Drug: Short-term infusion time of the following beta-lactam: meropenem; Drug: Short-term infusion time of the following beta-lactam: piperacillin/tazobactam; Drug: Short-term infusion time of the following beta-lactam: cefepime; Drug: Short-term infusion time of the following beta-lactam: ceftriaxone

pediatric patients, extended infusion (P, EI) and neonatal patients, extended infusion (N, EI)

EXPERIMENTAL

subset P: 28 days - 17 years subset N: term or pre-term infants \< 28 days of post-natal age, or PMA\* \< 44 weeks \*postmenstrual age

Drug: Extended infusion time of the following beta-lactam: meropenem; Drug: Extended infusion time of the following beta-lactam: piperacillin/tazobactam; Drug: Extended infusion time of the following beta-lactam: cefepime; Drug: Extended infusion time of the following beta-lactam: ceftriaxone

Interventions

Extended infusion time of the following beta-lactam: meropenem DRUG

Group extended infusion (EI): Duration of infusion is 3 hours (h) Subset paediatric (P): The doses of beta-lactams are (q…h= every…hours): \- meropenem (MPM): 30 mg/kg or 40 mg/kg for meningitis q8h (max. 2 g q8h) Subset neonatal (N): The doses of beta-lactams are as recommended by NeoFax® (MerativeTM Micromedex® database), based on postmenstrual age (PMA) and postnatal age.

pediatric patients, extended infusion (P, EI) and neonatal patients, extended infusion (N, EI)

Short-term infusion time of the following beta-lactam: meropenem DRUG

Group short-term infusion (SI): Duration of infusion is 0.5 hour (h) Subset paediatric (P): The doses of beta-lactams are (q…h= every…hours): \- meropenem (MPM): 30 mg/kg or 40 mg/kg for meningitis q8h (max. 2 g q8h) Subset neonatal (N): The doses of beta-lactams are as recommended by NeoFax® (MerativeTM Micromedex® database), based on postmenstrual age (PMA) and postnatal age.

pediatric patients, short-term infusion (P, SI) and neonatal patients, short-term infusion (N, SI)

Extended infusion time of the following beta-lactam: piperacillin/tazobactam DRUG

Group extended infusion (EI): Duration of infusion is 3 hours (h) Subset paediatric (P): The doses of beta-lactams are (q…h= every…hours): \- piperacillin/tazobactam (TZP): 90 mg/kg piperacillin q6h for non-immunosuppressed patients and 100 mg/kg piperacillin q6h for immunosuppressed patients (max. 4.5 g piperacillin/tazobactam per dose) Subset neonatal (N): The doses of beta-lactams are as recommended by NeoFax® (MerativeTM Micromedex® database), based on postmenstrual age (PMA) and postnatal age.

pediatric patients, extended infusion (P, EI) and neonatal patients, extended infusion (N, EI)

Extended infusion time of the following beta-lactam: cefepime DRUG

Group extended infusion (EI): Duration of infusion is 3 hours (h) Subset paediatric (P): The doses of beta-lactams are (q…h= every…hours): \- cefepime (CFP): 30-50 mg/kg q8h or q12h (\>1 month: 30 mg/kg every 8-12 hours, 2 months-17 years (bodyweight up to 41 kg): 50 mg/kg every 8-12 hours (max. 2 g per dose; increased dose \[q8h\] used for severe infection and febrile neutropenia) Subset neonatal (N): The doses of beta-lactams are as recommended by NeoFax® (MerativeTM Micromedex® database), based on postmenstrual age (PMA) and postnatal age.

pediatric patients, extended infusion (P, EI) and neonatal patients, extended infusion (N, EI)

Extended infusion time of the following beta-lactam: ceftriaxone DRUG

Group extended infusion (EI): Duration of infusion is 3 hours (h) Subset paediatric (P): The doses of beta-lactams are (q…h= every…hours): \- ceftriaxone (CTX): 50 mg/kg q12h (max. 4 g per day) Subset neonatal (N): The doses of beta-lactams are as recommended by NeoFax® (MerativeTM Micromedex® database), based on postmenstrual age (PMA) and postnatal age.

pediatric patients, extended infusion (P, EI) and neonatal patients, extended infusion (N, EI)

Short-term infusion time of the following beta-lactam: piperacillin/tazobactam DRUG

Group short-term infusion (SI): Duration of infusion is 0.5 hour (h) Subset paediatric (P): The doses of beta-lactams are (q…h= every…hours): \- piperacillin/tazobactam (TZP): 90 mg/kg piperacillin q6h for non-immunosuppressed patients and 100 mg/kg piperacillin q6h for immunosuppressed patients (max. 4.5 g piperacillin/tazobactam per dose) Subset neonatal (N): The doses of beta-lactams are as recommended by NeoFax® (MerativeTM Micromedex® database), based on postmenstrual age (PMA) and postnatal age.

pediatric patients, short-term infusion (P, SI) and neonatal patients, short-term infusion (N, SI)

Short-term infusion time of the following beta-lactam: cefepime DRUG

Group short-term infusion (SI): Duration of infusion is 0.5 hour (h) Subset paediatric (P): The doses of beta-lactams are (q…h= every…hours): \- cefepime (CFP): 30-50 mg/kg q8h or q12h (\>1 month: 30 mg/kg every 8-12 hours, 2 months-17 years (bodyweight up to 41 kg): 50 mg/kg every 8-12 hours (max. 2 g per dose; increased dose \[q8h\] used for severe infection and febrile neutropenia) Subset neonatal (N): The doses of beta-lactams are as recommended by NeoFax® (MerativeTM Micromedex® database), based on postmenstrual age (PMA) and postnatal age.

pediatric patients, short-term infusion (P, SI) and neonatal patients, short-term infusion (N, SI)

Short-term infusion time of the following beta-lactam: ceftriaxone DRUG

Group short-term infusion (SI): Duration of infusion is 0.5 hour (h) Subset paediatric (P): The doses of beta-lactams are (q…h= every…hours): \- ceftriaxone (CTX): 50 mg/kg q12h (max. 4 g per day) Subset neonatal (N): The doses of beta-lactams are as recommended by NeoFax® (MerativeTM Micromedex® database), based on postmenstrual age (PMA) and postnatal age.

pediatric patients, short-term infusion (P, SI) and neonatal patients, short-term infusion (N, SI)

Eligibility Criteria

• Age: 0 Hours - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• paediatric patients (0-17 years of age) with suspected or confirmed bacterial infection who are treated in a PICU or NICU and diagnosed with sepsis with a total Phoenix Sepsis Score ≥2 points, and the infection is clinically probable or confirmed by microbiological culture (e.g. from a blood culture, cerebrospinal fluid, urine, trachea, wound, etc.), excluding contamination;
• who are receiving β-lactams including meropenem, piperacillin/tazobactam, cefepime and ceftriaxone;
• written consent of the parent or guardian is obtained.

You may not qualify if:

• palliative care patients;
• patients participating in other drug trials;
• patients with impaired renal function if dosing modification is required (estimated Glomerular Filtration Rate \[eGFR\]\<50 mL/min/1.73m2 for meropenem, cefepime, and piperacillin/tazobactam; eGFR\<10 mL/min/1.73m2 for ceftriaxone);
• patients undergoing plasmapheresis (TPE);
• patients undergoing extracorporeal therapy (continuous kidney replacement therapy \[CKRT\] or extracorporeal membrane oxygenation \[ECMO\]);
• β-lactam allergy;
• patients admitted from another institution or department who have been on the same β-lactam treatment for more than 24 hours;
• pregnancy.

Sponsors & Collaborators

• Semmelweis University: lead

Study Sites (2)

Pediatric Center (Bókay Street Department), Semmelweis University

Budapest, 1083, Hungary

Location

Pediatric Center (Tűzoltó Street Department), Semmelweis University

Budapest, 1094, Hungary

Location

Related Publications (10)

• Andre P, Diezi L, Dao K, Crisinel PA, Rothuizen LE, Chtioui H, Decosterd LA, Diezi M, Asner S, Buclin T. Ensuring Sufficient Trough Plasma Concentrations for Broad-Spectrum Beta-Lactam Antibiotics in Children With Malignancies: Beware of Augmented Renal Clearance! Front Pediatr. 2022 Jan 5;9:768438. doi: 10.3389/fped.2021.768438. eCollection 2021.

  PMID: 35083184 BACKGROUND

• Van Der Heggen T, Dhont E, Willems J, Herck I, Delanghe JR, Stove V, Verstraete AG, Vanhaesebrouck S, De Paepe P, De Cock PAJG. Suboptimal Beta-Lactam Therapy in Critically Ill Children: Risk Factors and Outcome. Pediatr Crit Care Med. 2022 Jul 1;23(7):e309-e318. doi: 10.1097/PCC.0000000000002951. Epub 2022 Apr 15.

  PMID: 35426861 BACKGROUND

• O'Keefe K, Denny KJ, Le Marsney R, McCullough J, Gilholm P, Budai KA, Beranger A, Lodi C, Obeidat M, Ragonnet G, Wacharachaisurapol N, Roberts JA, Gibbons KS, Raman S. Prolonged Versus Intermittent Beta-Lactam Antibiotic Infusions in Paediatric Critical Care: A Systematic Review and Meta-Analysis. J Paediatr Child Health. 2026 Feb;62(2):160-170. doi: 10.1111/jpc.70275. Epub 2025 Dec 27.

  PMID: 41454710 BACKGROUND

• Briand A, Bernier L, Pincivy A, Roumeliotis N, Autmizguine J, Marsot A, Metras ME, Thibault C. Prolonged Beta-Lactam Infusions in Children: A Systematic Review and Meta-Analysis. J Pediatr. 2024 Dec;275:114220. doi: 10.1016/j.jpeds.2024.114220. Epub 2024 Aug 2.

  PMID: 39097265 BACKGROUND

• Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Kaukonen KM, Koulenti D, Martin C, Montravers P, Rello J, Rhodes A, Starr T, Wallis SC, Lipman J; DALI Study. DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014 Apr;58(8):1072-83. doi: 10.1093/cid/ciu027. Epub 2014 Jan 14.

  PMID: 24429437 BACKGROUND

• Zhou P, Zhang Y, Wang Z, Ying Y, Xing Y, Tong X, Zhai S. Extended or Continuous Infusion of Carbapenems in Children with Severe Infections: A Systematic Review and Narrative Synthesis. Antibiotics (Basel). 2021 Sep 9;10(9):1088. doi: 10.3390/antibiotics10091088.

  PMID: 34572670 BACKGROUND

• Hartman SJF, Bruggemann RJ, Orriens L, Dia N, Schreuder MF, de Wildt SN. Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature. Clin Pharmacokinet. 2020 Feb;59(2):173-205. doi: 10.1007/s40262-019-00813-w.

  PMID: 31432468 BACKGROUND

• Cies JJ, Moore WS 2nd, Enache A, Chopra A. beta-lactam Therapeutic Drug Management in the PICU. Crit Care Med. 2018 Feb;46(2):272-279. doi: 10.1097/CCM.0000000000002817.

  PMID: 29112080 BACKGROUND

• Imburgia TA, Kussin ML. A Review of Extended and Continuous Infusion Beta-Lactams in Pediatric Patients. J Pediatr Pharmacol Ther. 2022;27(3):214-227. doi: 10.5863/1551-6776-27.3.214. Epub 2022 Mar 21.

  PMID: 35350159 BACKGROUND

• Budai KA, Timar AE, Obeidat M, Mate V, Nagy R, Harnos A, Kiss-Dala S, Hegyi P, Garami M, Hanko B, Lodi C. Extended infusion of beta-lactams significantly reduces mortality and enhances microbiological eradication in paediatric patients: a systematic review and meta-analysis. EClinicalMedicine. 2023 Nov 2;65:102293. doi: 10.1016/j.eclinm.2023.102293. eCollection 2023 Nov.

  PMID: 38021371 BACKGROUND

MeSH Terms

Conditions

Infections; Sepsis

Interventions

Tazobactam

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Kinga Anna Budai

CONTACT

+36206632915; budai.kinga@semmelweis.hu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2026
• First Posted: March 20, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

HU (2)