E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neonatal probable bacterial infection |
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E.1.1.1 | Medical condition in easily understood language |
neonatal probable bacterial infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
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 |
To demonstrate the non-inferiority of intravenous-to-oral antibiotic switch therapy in clinically stable neonates with probable bacterial infection compared to a complete course of intravenous antibiotic therapy |
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E.2.2 | Secondary objectives of the trial |
• To describe the pharmacokinetics of oral amoxicillin/clavulanic acid in neonates • To quantify the cost-effectiveness of oral antimicrobial switch therapy in neonates • To study antimicrobial resistance and modification of the gut microbiome in relation to type and delivery of antibiotics.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Neonates, ≥ 35+0 weeks of gestation, 0-28 days old, ≥ 2.0 kg.
• probable bacterial infection (clinical symptoms and/or maternal risk factors and elevated inflammatory parameters (elevated PCT according to age-related normogram and/or elevated CRP)) for which empiric broad-spectrum antimicrobial treatment was initiated and need to be continued for > 48 hours at the discretion of the treating physician • reassuring level and trends of inflammatory parameters 48-72 hours after initiation of antimicrobial treatment • clinically stable • tolerates oral feeding and/or liquids without overt vomiting • written informed consent of parents or legal representatives
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E.4 | Principal exclusion criteria |
• proven bloodstream infection, failed blood culture • severe localized infection such as meningitis, osteomyelitis, necrotizing enterocolitis (pneumonia and urinary tract infection excluded) • severe clinical sepsis on admission (compromised circulation; need for mechanical ventilation) • known colonization with resistant bacteria such as MRSA, ESBL-producing bacteria • continuous need for central venous line (umbilical venous catheter, PICC) • clinicians’ decision to continue with intravenous antibiotics because of other reasons • parents’ inability to administer medication because of social reasons or language difficulties
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E.5 End points |
E.5.1 | Primary end point(s) |
Bacterial (re)-infection within 28 days after finishing of antimicrobial therapy ((defined as clinical signs and symptoms of bacterial infection and fever (> 38.0 deg C) or undertemperature (< 36.0 deg C) and elevated inflammatory parameters (CRP, PCT) and need for prolonged (> 48 h) antibiotic treatment)). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
28 days after finishing treatment |
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E.5.2 | Secondary end point(s) |
• duration of hospitalization • percentage re-admission • total costs and cost-effectiveness • clinical side effects of antibiotics • pharmacokinetic profile of oral amoxicillin • pharmacokinetic profile of oral clavulanic acid • quality of life at day 7, 14, 21, 28, 35 (painful procedures; breastfeeding; sleep quality; gastro-intestinal symptoms; parental satisfaction) • nosocomial infections • gut microbial flora profile and antimicrobial resistance genes
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
intravenous broad spectrum antibiotics |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | No |
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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last visit of last subject |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |