The main objective is to determine in what optimal dose PTX should be used in preterm infants suffering from sepsis. Previous clinical studies have already indicated the safety of the drug in preterm infants.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Dose optimisation will be based on the clinical and biochemical (CRP, IL-6,
PCT, TNF-a) response after 3 days in comparison to baseline and on adverse drug
effects.
Secondary outcome
Secondary study parameters include the evaluation of longitudinally determined
91 inflammatory markers (Olink proteomics) and metabolomics of the whole
inflammatory panel, to further understand the inflammatory and immunological
changes of preterm infants during sepsis with PTX treatment and the
pharmacokinetics of PTX and its metabolites in preterm infants. A target
concentration of PTX and its metabolites will be calculated and PK/PD model for
PTX will be developed.
Background summary
Sepsis is a very important cause of death in preterm infants. Survival from
sepsis is often related to severe short and long term morbidity. Despite
optimal antibiotic treatment, immaturity of the immune system in preterm
neonates causes this severe sepsis related mortality and morbidity. There is
strong indications that preterm neonates with sepsis could benefit, next to
antibiotics, from treatment with pentoxifylline (PTX). PTX which is registered
for adults with intermittent claudication, is already used in preterm neonates
with sepsis. Knowledge about optimal dosing is however limited.
Study objective
The main objective is to determine in what optimal dose PTX should be used in
preterm infants suffering from sepsis. Previous clinical studies have already
indicated the safety of the drug in preterm infants.
Study design
Dose optimisation study in preterm born infants with late onset sepsis and
increased inflammation. In this study different dosages will be evaluated, with
dosage step-up and step-down in every 3 patients. Starting dose will be the
dose as described in all previous studies. We expect that around 30 included
infants are needed to determine the optimal dose using this study design.
Subsequently, we will validate this optimal dose in 10 preterm neonates
Intervention
The intervention consists of intravenously administered pentoxifylline (PTX).
Study burden and risks
PTX is already used at our NICU for patients with sepsis, but data on the
dose/response curve do not exist. PTX has already been shown to have beneficial
effects in humans and animal models of sepsis, especially in preterm infants. A
meta-analysis showed that PTX increases the survival of preterm infants
suffering from sepsis and suggests that PTX is well tolerated. No severe side
effects have been detected in previous studies or in clinical practice of
preterm infants .We do expect a therapeutic gain for participants of the study
because of the expected benefits from optimized PTX treatment. Improved outcome
of neonatal sepsis is expected. During the study a limited amount of additional
blood will be collected either from arterial lines or during routine blood
drawing. No extra heelsticks or venipunctures will be performed for the study.
A maximum amount of 3% of the total blood volume is used for research purposes
in a 4 weeks period. Urine will be collected non-invasively. No further
additional burden is expected.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
- Neonates with gestational age <30 weeks
- suspected of late onset sepsis with blood drawn for blood culture and
inflammatory biomarkers
- IL-6 > 500 pg/ml and/or CRP > 50 mg/L
Exclusion criteria
- PTX therapy cannot be started within 24 hours of start of antibiotic
treatment.
- Patients with known major congenital defects (e.g. congenital heart disease,
pulmonary, or gastrointestinal anomalies) will also be excluded.
- If subjects have IL-6 values exceeding 25000 pg/mL at time of onset they will
also be excluded. High IL-6 values represent severe episodes of sepsis and high
IL-6 values are associated with high mortality rates.
- Patients who already participated in this trial during an earlier episode of
late onset sepsis.
- Patients with pH below 7 in two consecutive blood samples, with at least 1
hour between the blood samples, at start of sepsis episode.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002020-33-NL |
| Other | EudraCT nummer 2019-002020-33 |
| CCMO | NL70075.078.19 |