E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neonatal late onset sepsis |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053598 |
E.1.2 | Term | Late onset neonatal sepsis |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
- To further understand the inflammatory and immunological changes of preterm infants during sepsis with PTX treatment. We will longitudinally evaluate 91 inflammatory markers (Olink proteomics) and metabolomics of the whole inflammatory panel, . - To study the pharmacokinetics of PTX and its metabolites in preterm infants - To calculate a target concentration for PTX and its metabolites and develop a PK/PD model |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Neonates with gestational age <30 weeks - Suspected of sepsis with blood drawn for blood culture and inflammatory biomarkers - IL-6 > 500 pg/ml or if CRP > 50 mg/L |
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E.4 | Principal exclusion criteria |
- PTX therapy cannot be started within 24 hours of start of antibiotic treatment. - Patients with 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose optimisation will be based on the clinical and biochemical (CRP, IL-6, PCT, TNF-a) effects and on adverse drug effects. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints include the evaluation of longitudinally determined 91 inflammatory markers (Olink proteomics) and metabolomics of the whole inflammatory panel. Furthermore a target concentration of PTX and its metabolites will be calculated and PK/PD model for PTX will be developed.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of PTX-treatment of the last patient in the prospective dose evaluation. Last visit of the last subject is not applicable in this setting because the patients are already hospitalized. The patients will probably stay at the NICU for a longer time than the PTX treatment due to the prematurity. This does not differ from the expected normal treatment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 28 |