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Pentoxifylline Dose Optimization in Neonatal Sepsis

Primary Purpose

Neonatal Late Onset Sepsis

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pentoxifylline
Sponsored by
Erasmus Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neonatal Late Onset Sepsis focused on measuring Pentoxifylline, preterm infants, sepsis treatment, dose optimization

Eligibility Criteria

undefined - 30 Weeks (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Preterm born 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:

  • pentoxifylline therapy cannot be started within 24 hours of start of antibiotic treatment.
  • Major congenital defect (e.g. congenital heart disease, pulmonary, or gastrointestinal anomalies).
  • IL-6 values exceeding 25000 pg/mL at time of onset. High IL-6 values represent severe episodes of sepsis and high IL-6 values are associated with high mortality rates.
  • Already participated in this trial during an earlier episode of late onset sepsis.
  • PH below 7 in two consecutive blood samples, with at least 1 hour between the blood samples, at start of sepsis episode.

Sites / Locations

  • Erasmus MC Sophia Children's HospitalRecruiting
  • University Hospital PoznanRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Pentoxifylline therapy 2,5 mg/kg/h for 3 hours.

Pentoxifylline therapy 2,5 mg/kg/h for 6 hours

Pentoxifylline therapy 5 mg/kg/h for 6 hours.

Pentoxifylline therapy 5 mg/kg/h for 12 hours.

Pentoxifylline therapy 5 mg/kg/h for 18 hours.

Pentoxifylline therapy 5 mg/kg/h for 24 hours.

Arm Description

This is a dose optimization study, different dosages will be tested, the lowest dosage that will be tested is 2,5 mg/kg/h for 3 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.

The second lowest dosage that will be tested is 2,5 mg/kg/h for 6 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.

The third lowest dosage, is the start dosage and the dosage that is already used in other clinical studies: 5 mg/kg/h for 6 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.

The fourth dosage that is tested is 5 mg/kg/h for 12 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease..

The fifth dosage that is tested is 5 mg/kg/h for 18 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.

The sixth dosage that is tested is 5 mg/kg/h for 24 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.

Outcomes

Primary Outcome Measures

Adequate pentoxifylline dose
Adequate pentoxifylline doses are determined by 3 co-primary outcome variables: Adequate biochemical response: CRP will be measured in blood at time of onset and 24 , 48 and 72 hours after onset. An area under the curve (AUC) will be calculated for each patient. An area under the curve below the 25th percentile of an historical cohort is considered to be adequate. Adequate clinical outcome: if a patient has one of the following criteria, clinical outcome is considered inadequate: mortality, necrotizing enterocolitis greater than Bell stage 3, pH below 7 in 2 consecutive blood samples with at least 1 hour between the 2 samples after start of sepsis treatment and/or the need to start NO therapy with indication pulmonary hypertension after start of sepsis treatment. No severe side effects/adverse drug reaction

Secondary Outcome Measures

The levels of 91 inflammatory Olink proteomics markers measured in blood plasma and sepsis
The inflammatory panel from Olink Proteomics will be used (link: https://www.olink.com/products/inflammation/) to measure 91 inflammatory proteomics will be measured in blood plasma during sepsis treatment. Olink proteomics are measured in Normalized Protein eXpression (NPX) (link: https://www.olink.com/question/what-is-npx/). The authors want is to further understand the inflammatory and immunological changes of preterm infants during sepsis with pentoxifylline treatment. This analyses will be exploratory, seeing that proteomics haven't been frequently used in neonatal sepsis (research). The aim is to find differential proteomic patterns among patients with gram negative sepsis, gram positive sepsis, culture negative sepsis or no infection. The authors will report proteomic patterns associated with sepsis.
The levels of metabolomic biomarkers of the signalling and peroxidised lipid platform measured in blood plasma and sepsis
Metabolomics of the signalling and peroxidised lipid platform will be measured in blood plasma. The authors want to further understand the inflammatory and immunological changes of preterm infants during sepsis with pentoxifylline treatment. This platform covers the following classes of metabolomics: Eicosanoids / Oxylipins Endocannabinoids Isoprostanes Nitro fatty acids Lysophopholipids & Sphingosine-1-phosphate Polyunsaturated free fatty acids Bile acids The aim is to find differential metabolomics patterns among patients with gram negative sepsis, gram positive sepsis, culture negative sepsis or no infection. The authors will report metabolomic patterns associated with sepsis. Metabolomics measurements are performed using mass spectrometry.
Pentoxifylline and metabolites levels in blood plasma during sepsis treatment
Pentoxifylline concentrations will be analyzed in a pharmacokinetic model and will be integrated with pharmacodynamics data(biochemical response, side effects) and covariates(post menstrual age, weight, morbidity, etc). The authors will report effective pentoxifylline and metabolites concentrations (µg/ml) and concentrations (µg/ml) that might result in side-effects.
The levels of 91 inflammatory Olink proteomics markers measured in blood plasma and clinical outcome
This will be exploratory, seeing that proteomics haven't been frequently used in neonatal sepsis (research). The predictive value of differential proteomic levels and changes in levels in predicting the clinical outcome (e.g. predicting hypotension, respiratory deterioration, etc.) will be evaluated. The inflammatory panel form Olink Proteomics will be used (link: https://www.olink.com/products/inflammation/). The authors will report proteomic levels and patterns in Normalized Protein eXpression (NPX) (link: https://www.olink.com/question/what-is-npx/).
The levels of metabolomic biomarkers of the signalling and peroxidised lipid platform measured in blood plasma and clinical outcome
This will be exploratory, seeing that metabolomics haven't been frequently used in neonatal sepsis (research). The predictive value of differential metabolomic patterns in predicting the clinical outcome (e.g. predicting hypotension, respiratory deterioration, etc.) will be evaluated. Metabolomics of the signalling and peroxidised lipid platform will be measured in blood plasma. This platform covers the following classes of metabolomics: Eicosanoids / Oxylipins Endocannabinoids Isoprostanes Nitro fatty acids Lysophopholipids & Sphingosine-1-phosphate Polyunsaturated free fatty acids Bile acids The authors will report metabolomics levels and patterns by measuring metabolomics using mass spectrometry.
The levels of 91 inflammatory Olink proteomics markers measured in blood plasma and pentoxifylline and metabolites levels in blood plasma during sepsis treatment
Associations between the proteomic levels and pentoxifylline exposure will be explored by visual inspection (i.e. scatter plots) and statistical comparisons as needed. Pentoxifylline exposure will be reported by pentoxifylline and metabolites concentrations (µg/ml) and proteomic levels will be reported in Normalized Protein eXpression (NPX) (link: https://www.olink.com/question/what-is-npx/).
The levels of metabolomic biomarkers of the signalling and peroxidised lipid platform measured in blood plasma and pentoxifylline and metabolites levels in blood plasma during sepsis treatment
Associations between the metabolomic biomarkers of the signalling and peroxidised lipid platform and pentoxifylline exposure will be explored by visual inspection (i.e. scatter plots) and statistical comparisons as needed. This platform covers the following classes of metabolomics: Eicosanoids / Oxylipins Endocannabinoids Isoprostanes Nitro fatty acids Lysophopholipids & Sphingosine-1-phosphate Polyunsaturated free fatty acids Bile acids Pentoxifylline exposure will be reported by pentoxifylline and metabolites concentrations (µg/ml) and metabolomics levels by measuring metabolomics using mass spectrometry.

Full Information

First Posted
June 21, 2019
Last Updated
June 21, 2022
Sponsor
Erasmus Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04152980
Brief Title
Pentoxifylline Dose Optimization in Neonatal Sepsis
Official Title
Pentoxifylline Dose Optimization in Preterm Neonatal Late Onset Sepsis
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 12, 2020 (Actual)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 pg/mL and/ or a C- reactive protein above 50 mg/L is needed at initiation of pentoxifylline therapy. Intervention: The intervention consists of intravenously administered pentoxifylline. Main study parameters/endpoints: 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 effects/adverse 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 dose/response 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neonatal Late Onset Sepsis
Keywords
Pentoxifylline, preterm infants, sepsis treatment, dose optimization

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
Model Description
Prospective dose optimizing 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. The first 3 patients will receive a dose of 5 mg/k/h for 6 h per day, comparable to the dose that has been used before in trials. Upward or downward dose adjustments for the following cohort of 3 patients will be considered. If the dose is effective, the next 3 patients will receive a lower dose, in order to find the lowest effective dose. After the dose optimization study an additional cohort of 10 patients will be treated with the determined optimal dose as a validation of this dose.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pentoxifylline therapy 2,5 mg/kg/h for 3 hours.
Arm Type
Experimental
Arm Description
This is a dose optimization study, different dosages will be tested, the lowest dosage that will be tested is 2,5 mg/kg/h for 3 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.
Arm Title
Pentoxifylline therapy 2,5 mg/kg/h for 6 hours
Arm Type
Experimental
Arm Description
The second lowest dosage that will be tested is 2,5 mg/kg/h for 6 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.
Arm Title
Pentoxifylline therapy 5 mg/kg/h for 6 hours.
Arm Type
Experimental
Arm Description
The third lowest dosage, is the start dosage and the dosage that is already used in other clinical studies: 5 mg/kg/h for 6 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.
Arm Title
Pentoxifylline therapy 5 mg/kg/h for 12 hours.
Arm Type
Experimental
Arm Description
The fourth dosage that is tested is 5 mg/kg/h for 12 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease..
Arm Title
Pentoxifylline therapy 5 mg/kg/h for 18 hours.
Arm Type
Experimental
Arm Description
The fifth dosage that is tested is 5 mg/kg/h for 18 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.
Arm Title
Pentoxifylline therapy 5 mg/kg/h for 24 hours.
Arm Type
Experimental
Arm Description
The sixth dosage that is tested is 5 mg/kg/h for 24 hours every 24 hours for 3 to 6 days. The decision to prolong therapy after 3 days of therapy is made by the treating physician, depending on the clinical state of the patient and the severity of disease.
Intervention Type
Drug
Intervention Name(s)
Pentoxifylline
Other Intervention Name(s)
Trental
Intervention Description
The intervention consists of intravenously administered pentoxifylline. Pentoxifylline , a methylxanthine, is an off patent drug for neonates and currently registered for peripheral artery disease treatment in adults. Pentoxifylline acts as a cyclic adenosine monophosphate(cAMP)-phosphodiesterase inhibitor that suppresses tumor necrosis factor alfa (TNF-α) and modulates important parts of the inflammatory response and also reduces the production of other inflammatory cytokines, such as IL-1α, IL-6, and IL-8.
Primary Outcome Measure Information:
Title
Adequate pentoxifylline dose
Description
Adequate pentoxifylline doses are determined by 3 co-primary outcome variables: Adequate biochemical response: CRP will be measured in blood at time of onset and 24 , 48 and 72 hours after onset. An area under the curve (AUC) will be calculated for each patient. An area under the curve below the 25th percentile of an historical cohort is considered to be adequate. Adequate clinical outcome: if a patient has one of the following criteria, clinical outcome is considered inadequate: mortality, necrotizing enterocolitis greater than Bell stage 3, pH below 7 in 2 consecutive blood samples with at least 1 hour between the 2 samples after start of sepsis treatment and/or the need to start NO therapy with indication pulmonary hypertension after start of sepsis treatment. No severe side effects/adverse drug reaction
Time Frame
3 days
Secondary Outcome Measure Information:
Title
The levels of 91 inflammatory Olink proteomics markers measured in blood plasma and sepsis
Description
The inflammatory panel from Olink Proteomics will be used (link: https://www.olink.com/products/inflammation/) to measure 91 inflammatory proteomics will be measured in blood plasma during sepsis treatment. Olink proteomics are measured in Normalized Protein eXpression (NPX) (link: https://www.olink.com/question/what-is-npx/). The authors want is to further understand the inflammatory and immunological changes of preterm infants during sepsis with pentoxifylline treatment. This analyses will be exploratory, seeing that proteomics haven't been frequently used in neonatal sepsis (research). The aim is to find differential proteomic patterns among patients with gram negative sepsis, gram positive sepsis, culture negative sepsis or no infection. The authors will report proteomic patterns associated with sepsis.
Time Frame
If possible at 3 days old, 1 hour after sepsis onset, 6, 24, 48 hours after onset and at 7 days after sepsis onset.
Title
The levels of metabolomic biomarkers of the signalling and peroxidised lipid platform measured in blood plasma and sepsis
Description
Metabolomics of the signalling and peroxidised lipid platform will be measured in blood plasma. The authors want to further understand the inflammatory and immunological changes of preterm infants during sepsis with pentoxifylline treatment. This platform covers the following classes of metabolomics: Eicosanoids / Oxylipins Endocannabinoids Isoprostanes Nitro fatty acids Lysophopholipids & Sphingosine-1-phosphate Polyunsaturated free fatty acids Bile acids The aim is to find differential metabolomics patterns among patients with gram negative sepsis, gram positive sepsis, culture negative sepsis or no infection. The authors will report metabolomic patterns associated with sepsis. Metabolomics measurements are performed using mass spectrometry.
Time Frame
If possible at 3 days old, 1 hour after sepsis onset, 6, 24, 48 hours after onset and at 7 days after sepsis onset.
Title
Pentoxifylline and metabolites levels in blood plasma during sepsis treatment
Description
Pentoxifylline concentrations will be analyzed in a pharmacokinetic model and will be integrated with pharmacodynamics data(biochemical response, side effects) and covariates(post menstrual age, weight, morbidity, etc). The authors will report effective pentoxifylline and metabolites concentrations (µg/ml) and concentrations (µg/ml) that might result in side-effects.
Time Frame
3 days after start of pentoxifylline treatment
Title
The levels of 91 inflammatory Olink proteomics markers measured in blood plasma and clinical outcome
Description
This will be exploratory, seeing that proteomics haven't been frequently used in neonatal sepsis (research). The predictive value of differential proteomic levels and changes in levels in predicting the clinical outcome (e.g. predicting hypotension, respiratory deterioration, etc.) will be evaluated. The inflammatory panel form Olink Proteomics will be used (link: https://www.olink.com/products/inflammation/). The authors will report proteomic levels and patterns in Normalized Protein eXpression (NPX) (link: https://www.olink.com/question/what-is-npx/).
Time Frame
If possible at 3 days old, 1 hour after sepsis onset, 6, 24, 48 hours after onset and at 7 days after sepsis onset.
Title
The levels of metabolomic biomarkers of the signalling and peroxidised lipid platform measured in blood plasma and clinical outcome
Description
This will be exploratory, seeing that metabolomics haven't been frequently used in neonatal sepsis (research). The predictive value of differential metabolomic patterns in predicting the clinical outcome (e.g. predicting hypotension, respiratory deterioration, etc.) will be evaluated. Metabolomics of the signalling and peroxidised lipid platform will be measured in blood plasma. This platform covers the following classes of metabolomics: Eicosanoids / Oxylipins Endocannabinoids Isoprostanes Nitro fatty acids Lysophopholipids & Sphingosine-1-phosphate Polyunsaturated free fatty acids Bile acids The authors will report metabolomics levels and patterns by measuring metabolomics using mass spectrometry.
Time Frame
If possible at 3 days old, 1 hour after sepsis onset, 6, 24, 48 hours after onset and at 7 days after sepsis onset.
Title
The levels of 91 inflammatory Olink proteomics markers measured in blood plasma and pentoxifylline and metabolites levels in blood plasma during sepsis treatment
Description
Associations between the proteomic levels and pentoxifylline exposure will be explored by visual inspection (i.e. scatter plots) and statistical comparisons as needed. Pentoxifylline exposure will be reported by pentoxifylline and metabolites concentrations (µg/ml) and proteomic levels will be reported in Normalized Protein eXpression (NPX) (link: https://www.olink.com/question/what-is-npx/).
Time Frame
If possible at onset of sepsis and 24 and 48 hours after onset of sepsis
Title
The levels of metabolomic biomarkers of the signalling and peroxidised lipid platform measured in blood plasma and pentoxifylline and metabolites levels in blood plasma during sepsis treatment
Description
Associations between the metabolomic biomarkers of the signalling and peroxidised lipid platform and pentoxifylline exposure will be explored by visual inspection (i.e. scatter plots) and statistical comparisons as needed. This platform covers the following classes of metabolomics: Eicosanoids / Oxylipins Endocannabinoids Isoprostanes Nitro fatty acids Lysophopholipids & Sphingosine-1-phosphate Polyunsaturated free fatty acids Bile acids Pentoxifylline exposure will be reported by pentoxifylline and metabolites concentrations (µg/ml) and metabolomics levels by measuring metabolomics using mass spectrometry.
Time Frame
If possible at onset of sepsis and 24 and 48 hours after onset of sepsis

10. Eligibility

Sex
All
Maximum Age & Unit of Time
30 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Preterm born 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: pentoxifylline therapy cannot be started within 24 hours of start of antibiotic treatment. Major congenital defect (e.g. congenital heart disease, pulmonary, or gastrointestinal anomalies). IL-6 values exceeding 25000 pg/mL at time of onset. High IL-6 values represent severe episodes of sepsis and high IL-6 values are associated with high mortality rates. Already participated in this trial during an earlier episode of late onset sepsis. PH below 7 in two consecutive blood samples, with at least 1 hour between the blood samples, at start of sepsis episode.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sinno Simons, MD, PhD
Phone
+0031 (0)107040704
Email
s.simons@erasmusmc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Rob Taal, MD, PhD
Phone
+0031 (0)107040704
Email
h.taal@erasmusmc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sinno Simons, MD, PhD
Organizational Affiliation
Erasmus Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Erasmus MC Sophia Children's Hospital
City
Rotterdam
ZIP/Postal Code
3000CB
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sinno Simons, MD PhD
Phone
0031107040704
Email
s.simons@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Irwin Reiss, MD PhD
Phone
00317040704
Email
i.reiss@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Sinno Simons, MD PhD
Facility Name
University Hospital Poznan
City
Poznan
ZIP/Postal Code
61-701
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Mazela
Email
janco@pol-med.com.pl

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The investigators have made a Data management plan in DMPonline in collaboration with local datamanager Dr. A Ham. The investigators plan to publish in an open access journal There is a management plan considering making data findable, accessible and intraoperable and reusable.
IPD Sharing Time Frame
Protocol, Statistical Analysis Plan and Informed Consent Form will be shared after the protocol has been approved by the medical ethical committee.
IPD Sharing Access Criteria
The data management plan is shared in a public area. The investigators intend to share our data after our clinical study report is published. Sharing of data will only occur after permission is given by the investigators.
IPD Sharing URL
https://dmponline.dcc.ac.uk/public_plans
Citations:
PubMed Identifier
7835945
Citation
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.
Results Reference
background
PubMed Identifier
8699856
Citation
Mandell GL. Cytokines, phagocytes, and pentoxifylline. J Cardiovasc Pharmacol. 1995;25 Suppl 2:S20-2. doi: 10.1097/00005344-199500252-00005.
Results Reference
background
PubMed Identifier
9251897
Citation
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.
Results Reference
background
PubMed Identifier
3927788
Citation
Schroer RH. Antithrombotic potential of pentoxifylline. A hemorheologically active drug. Angiology. 1985 Jun;36(6):387-98. doi: 10.1177/000331978503600608.
Results Reference
background
PubMed Identifier
10484426
Citation
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.
Results Reference
background
PubMed Identifier
8605790
Citation
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.
Results Reference
background
PubMed Identifier
25751631
Citation
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.
Results Reference
background
PubMed Identifier
21975745
Citation
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.
Results Reference
background
PubMed Identifier
34794420
Citation
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.
Results Reference
derived
Links:
URL
https://www.olink.com/products/inflammation/
Description
Olink Proteomics Inflammation Panel
URL
https://www.olink.com/question/what-is-npx/
Description
Olink Proteomics NPX unit of measurement

Learn more about this trial

Pentoxifylline Dose Optimization in Neonatal Sepsis

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