“How can a drug to treat claudication in adults save preterm newborns?”

Kurul, Şerife; Allegaert, Karel; Flint, Robert B.; Taal, H. Rob

doi:10.1007/s00431-020-03631-6

Cited by 2 publications

(3 citation statements)

References 27 publications

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“…In a recent Cochrane review including 6 relatively small studies, Pammi et al demonstrated that PTX improves survival in neonatal sepsis [15]. Unfortunately, as is the case for most drugs used in neonates, the optimal dosage has not yet been investigated with good quality dose seeking studies for this particular population and indication [8]. This has consequences for both research and clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…This has consequences for both research and clinical practice. In the subsequent placebo controlled trial, a sub-optimal dosage may be compared, leading to suboptimal findings or increased risk of adverse events [8]. The dosage regimen used in clinical practice might be suboptimal with either under-or overexposure.…”

Section: Discussionmentioning

confidence: 99%

“…Pentoxifylline (PTX), a methylxanthine, is currently registered only for peripheral artery disease treatment in adults and is used off label in newborn infants with sepsis. PTX is a promising therapeutic compound, which can be repurposed as adjuvant therapy next to antibiotics for preterm infants with sepsis [8]. PTX acts as a cAMPphosphodiesterase inhibitor that suppresses TNF-α and modulates important parts of the inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

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Protocol: Pentoxifylline optimal dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial)

et al. 2021

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Background Late onset sepsis is a leading cause of death and morbidity in preterm infants. Despite optimal antibiotic treatment, sepsis related mortality and morbidity is still high. Pentoxifylline (PTX) is a methylxanthine with promising immunomodulatory properties, which can be used as an additional therapy next to antibiotics in preterm infants. PTX is increasingly used off-label in neonatal intensive care units, however up till now no dose finding study has been done for PTX in this specific population. The aim of this study (PTX-trial) is to determine the optimal dose of PTX in preterm infants (gestational age < 30 weeks) with (suspected) late onset sepsis. Dose finding in this particular population is unique, since for most drugs used in neonates the optimal dosage has not been investigated in phase II dose-seeking studies. Methods The PTX-trial is a prospective open label sequential dose-optimization study with an adapted continual reassessment method. An up-and-down dose-response design will be used, with dose step-up and step-down titration after every 3 patients. The PTX starting dosage will be 30 mg/kg/day in 6 hours as described in most previous neonatal studies. Efficacy is defined by means of biochemical and clinical parameters. Toxicity in these vulnerable patients is unwarranted. The optimal dose is defined as the ED75 (i.e., clinically and chemically effective dose for 75% of patients) in preterm neonates with late onset sepsis. We plan to include 30 neonates to determine the optimal dose using this study design. Subsequently, the optimal dose will be validated in 10 additional preterm neonates. In parallel, pharmacokinetics of PTX and its metabolites will be described as well as longitudinal evaluation of metabolomics and proteomics. Discussion The study has been approved by the Regional Medical Ethics Board of Erasmus Medical Center University Rotterdam (MEC 2019-0477) and registered at Clinicaltrials.gov (NCT04152980). Results of the main trial and each of the secondary endpoints will be submitted for publications in peer-reviewed journals. Trial registration Clinicaltrials.gov, NCT04152980, Registered November 6th, 2019

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protocol: Pentoxifylline optimal dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial)

et al. 2021

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Stratified Management for Bacterial Infections in Late Preterm and Term Neonates: Current Strategies and Future Opportunities Toward Precision Medicine

Keij¹,

Achten²,

Tramper-Stranders³

et al. 2021

Front. Pediatr.

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Bacterial infections remain a major cause of morbidity and mortality in the neonatal period. Therefore, many neonates, including late preterm and term neonates, are exposed to antibiotics in the first weeks of life. Data on the importance of inter-individual differences and disease signatures are accumulating. Differences that may potentially influence treatment requirement and success rate. However, currently, many neonates are treated following a “one size fits all” approach, based on general protocols and standard antibiotic treatment regimens. Precision medicine has emerged in the last years and is perceived as a new, holistic, way of stratifying patients based on large-scale data including patient characteristics and disease specific features. Specific to sepsis, differences in disease susceptibility, disease severity, immune response and pharmacokinetics and -dynamics can be used for the development of treatment algorithms helping clinicians decide when and how to treat a specific patient or a specific subpopulation. In this review, we highlight the current and future developments that could allow transition to a more precise manner of antibiotic treatment in late preterm and term neonates, and propose a research agenda toward precision medicine for neonatal bacterial infections.

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“How can a drug to treat claudication in adults save preterm newborns?”

Cited by 2 publications

References 27 publications

Protocol: Pentoxifylline optimal dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial)

Protocol: Pentoxifylline optimal dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial)

Stratified Management for Bacterial Infections in Late Preterm and Term Neonates: Current Strategies and Future Opportunities Toward Precision Medicine

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