Ignite Creation Date:
2024-05-06 @ 1:53 PM
Last Modification Date:
2024-10-26 @ 1:21 PM
Study NCT ID:
NCT04152980
Status:
COMPLETED
Last Update Posted:
2022-06-22
First Post:
2019-06-21
Brief Title:
Pentoxifylline Dose Optimization in Neonatal Sepsis
Sponsor:
Erasmus Medical Center
Organization:
Erasmus Medical Center
Study Overview
Official Title:
Pentoxifylline Dose Optimization in Preterm Neonatal Late Onset Sepsis
Status:
COMPLETED
Status Verified Date:
2024-08
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Detailed Description:
Rationale 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 are strong indications that preterm neonates with sepsis could benefit next to antibiotics from treatment with pentoxifylline Pentoxifylline which is registered for adults with intermittent claudication is already used in preterm neonates with sepsis Knowledge about optimal dosing is however limited
Objective The main objective is to determine in what optimal dose pentoxifylline 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 Around 30 included neonates are expected to be needed to determine the optimal dose using this study design Subsequently The optimal dose will be validated in 10 preterm neonates
Study population Preterm born neonates with a gestational age below 30 weeks and suspected late onset sepsis and relevant inflammation are eligible for inclusion To quantify inflammation an interleukin-6 above 500 pgmL and or a C- reactive protein above 50 mgL is needed at initiation of pentoxifylline therapy
Intervention The intervention consists of intravenously administered pentoxifylline
Main study parametersendpoints Primary outcome is the optimal dose of pentoxifylline Optimized pentoxifylline dosage needs to be related with adequate biochemical response adequate clinical response and no severe side effectsadverse drug reaction In each patient it is determined if the patient has an adequate pentoxifylline dosage The dosage is considered to be adequate if the biochemical response is adequate and the clinical outcome is adequate with no severe side effects When 3 patients are treated with a certain dosage a decision will be made whether to increase or decrease the dosage for the next 3 patients If the dosage was considered inadequate at least 2 patients in whom the dosage was inadequate the dosage for the next patients will be increased If the dosage was considered adequate at least 2 patients in whom the dosage was adequate the dosage for the next patients will be decreased Secondary endpoints include further understanding the inflammatory and immunological changes of preterm infants during sepsis with pentoxifylline treatment by measuring metabolomic biomarkers of the signalling and peroxidised lipid platform and 91 inflammatory proteomics
Nature and extent of the burden and risks associated with participation benefit and group relatedness Pentoxifylline is already used at our neonatal intensive care unit for patients with sepsis but data on the doseresponse curve do not exist Pentoxifylline has already been shown to have beneficial effects in humans and animal models of sepsis especially in preterm infants A meta-analysis showed that pentoxifylline increases the survival of preterm infants suffering from sepsis and suggests that pentoxifylline is well tolerated No severe side effects have been detected in previous studies or in clinical practice of preterm infants A therapeutic gain for participants of the study is expected because of the expected benefits from optimized pentoxifylline 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 No further additional burden is expected
Objective The main objective is to determine in what optimal dose pentoxifylline 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 Around 30 included neonates are expected to be needed to determine the optimal dose using this study design Subsequently The optimal dose will be validated in 10 preterm neonates
Study population Preterm born neonates with a gestational age below 30 weeks and suspected late onset sepsis and relevant inflammation are eligible for inclusion To quantify inflammation an interleukin-6 above 500 pgmL and or a C- reactive protein above 50 mgL is needed at initiation of pentoxifylline therapy
Intervention The intervention consists of intravenously administered pentoxifylline
Main study parametersendpoints Primary outcome is the optimal dose of pentoxifylline Optimized pentoxifylline dosage needs to be related with adequate biochemical response adequate clinical response and no severe side effectsadverse drug reaction In each patient it is determined if the patient has an adequate pentoxifylline dosage The dosage is considered to be adequate if the biochemical response is adequate and the clinical outcome is adequate with no severe side effects When 3 patients are treated with a certain dosage a decision will be made whether to increase or decrease the dosage for the next 3 patients If the dosage was considered inadequate at least 2 patients in whom the dosage was inadequate the dosage for the next patients will be increased If the dosage was considered adequate at least 2 patients in whom the dosage was adequate the dosage for the next patients will be decreased Secondary endpoints include further understanding the inflammatory and immunological changes of preterm infants during sepsis with pentoxifylline treatment by measuring metabolomic biomarkers of the signalling and peroxidised lipid platform and 91 inflammatory proteomics
Nature and extent of the burden and risks associated with participation benefit and group relatedness Pentoxifylline is already used at our neonatal intensive care unit for patients with sepsis but data on the doseresponse curve do not exist Pentoxifylline has already been shown to have beneficial effects in humans and animal models of sepsis especially in preterm infants A meta-analysis showed that pentoxifylline increases the survival of preterm infants suffering from sepsis and suggests that pentoxifylline is well tolerated No severe side effects have been detected in previous studies or in clinical practice of preterm infants A therapeutic gain for participants of the study is expected because of the expected benefits from optimized pentoxifylline 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 No further additional burden is expected
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None