Pentoxifylline Dose Optimization in Neonatal Sepsis

Summary

Sepsis is a very important cause of death and morbidity in preterm infants. There are strong indications that preterm neonates with sepsis could benefit, next to antibiotics, from treatment with pentoxifylline (PTX). Knowledge about optimal dosing is however limited. This study is a dose optimization study using a step-up and step-down model. In order to find the optimal dose, the infusion of pentoxifylline in different dosages will be studied, next to antibiotics with 3 patients per dosage. After the dose optimization study an additional cohort of 10 patients will be treated with the found dosage as a validation of the dose.

Timeline

Start

2020-01-12

Primary completion

2022-10-31

Completion

2022-12-31

Publications

• Background Neuner P, Klosner G, Schauer E, Pourmojib M, Macheiner W, Grunwald C, Knobler R, Schwarz A, Luger TA, Schwarz T. Pentoxifylline in vivo down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha by human peripheral blood mononuclear cells. Immunology. 1994 Oct;83(2):262-7.
• Background Mandell GL. Cytokines, phagocytes, and pentoxifylline. J Cardiovasc Pharmacol. 1995;25 Suppl 2:S20-2. doi: 10.1097/00005344-199500252-00005.
• Background Windmeier C, Gressner AM. Pharmacological aspects of pentoxifylline with emphasis on its inhibitory actions on hepatic fibrogenesis. Gen Pharmacol. 1997 Aug;29(2):181-96. doi: 10.1016/s0306-3623(96)00314-x.
• Background Schroer RH. Antithrombotic potential of pentoxifylline. A hemorheologically active drug. Angiology. 1985 Jun;36(6):387-98. doi: 10.1177/000331978503600608.
• Background Yang S, Zhou M, Koo DJ, Chaudry IH, Wang P. Pentoxifylline prevents the transition from the hyperdynamic to hypodynamic response during sepsis. Am J Physiol. 1999 Sep;277(3):H1036-44. doi: 10.1152/ajpheart.1999.277.3.H1036.
• Background Zeni F, Pain P, Vindimian M, Gay JP, Gery P, Bertrand M, Page Y, Page D, Vermesch R, Bertrand JC. Effects of pentoxifylline on circulating cytokine concentrations and hemodynamics in patients with septic shock: results from a double-blind, randomized, placebo-controlled study. Crit Care Med. 1996 Feb;24(2):207-14. doi: 10.1097/00003246-199602000-00005.
• Background Pammi M, Haque KN. Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates. Cochrane Database Syst Rev. 2015 Mar 9;(3):CD004205. doi: 10.1002/14651858.CD004205.pub3.
• Background Haque KN, Pammi M. Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD004205. doi: 10.1002/14651858.CD004205.pub2.
• Kurul S, Taal HR, Flint RB, Mazela J, Reiss IKM, Allegaert K, Simons SHP. Protocol: Pentoxifylline optimal dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial). BMC Pediatr. 2021 Nov 18;21(1):517. doi: 10.1186/s12887-021-02975-8.

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