E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients admitted to the neonatal intensive care unit with single-organ respiratory failure |
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E.1.1.1 | Medical condition in easily understood language |
Patients admitted to the neonatal intensive care unit with single-organ respiratory failure |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053349 |
E.1.2 | Term | Pharmacokinetic study |
E.1.2 | System Organ Class | 100000004848 |
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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 |
- what are the pharmacokinetic parameters (distribution volume, distribution half-life, terminal half-life, context-sensitive half-life, clearance) of dexmedetomidine infusion in mechanically ventilated neonates with single-organ respiratory failure? - do size, age (postmenstrual, postconceptional, postnatal), co-medication, severity of illness, infusion length (covariates) contribute to a variability in exposure and response to dexmedetomidine in this population? - knowledge of the pharmacokinetic parameters of dexmedetomidine and their covariates will allow targeted dosing in this population |
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E.2.2 | Secondary objectives of the trial |
- does CYP2A6 and UDP-glucuronosyltransferase genotype (covariates) contribute to a variability in exposure and response to dexmedetomidine in this population? - describe the maturational trends in PK and PD in combining the observations in neonates with similar observations during childhood |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- patient age less than 1 month (adaptive design:step-down strategy for age) - patients with single-organ respiratory failure in need for analgosedation (guidance : Comfort neo score>14 or Numeric Rating Scale (NRS) score Pain (P)/Comfort (C)>4) - patients admitted to the neonatal intensive care or cardiac intensive care unit - expected to require at least 20 h of mechanical ventilation
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E.4 | Principal exclusion criteria |
- patients with neurologic conditions that prohibit an evaluation of adequate analgosedation - no arterial catheter in place at inclusion - patients who have received another investigational drug within 30 days - patients on continuous infusion with neuromuscular blockers - patients with a life expectancy <72h - patients with a known allergy to fentanyl - congenital or acquired heart block (grade 3) - sustained bradycardia - haemodynamically unstable patients (definition : Mean Arterial Pressure (MAP) lower than : gestational age (in weeks) – (absolute minimum for cardiac surgery patients: 40 mm Hg), eventually under dopamine infusion max. 15 mcg/kg/min and/or dobutamine infusion max. 15 mcg/kg/min) and/or epinephrine infusion: max 0,2 mcg/kg/min. More stringent criteria can be used based on an individual basis at the discretion of the attending neonatologist/intensivist. - patients with significant renal insufficiency (creatinine plasma level >1.5 mg/dl) - patients with significant hepatic insufficiency (as estimated by local investigators) - previous treatment with α2-adrenoreceptor agonist clonidine within 14 days - absence of parental consent
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E.5 End points |
E.5.1 | Primary end point(s) |
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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) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline and at least once every hour after start of dexmedetomidine. |
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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 | No |
E.6.4 | Safety | Yes |
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 | No |
E.6.10 | Pharmacogenetic | Yes |
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) | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 4 |
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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |