E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Infants with induced hypothermic treatment after perinatal asphyxia |
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E.1.1.1 | Medical condition in easily understood language |
Infants with induced hypothermic treatment after perinatal deficient supply of oxygen. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
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 |
The specific aims of this Project are to
•study the PK of fentanyl and clonidine in infants receiving induced hypothermic treatment after perinatal asphyxia using NONMEM® (Non-linear Mixed Effect Modelling) population based PK modelling.
• assess the effects of the drugs on brain function (PD) in these infants and relate the effects to drug concentration (PK/PD).
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E.2.2 | Secondary objectives of the trial |
• assess the effects of the drugs concentration (PK/PD) on to the physiological parameters (including NIRS) and the pain response (pain assessment scales and GSR) in these infants and relate the effects to drug concentration (PK/PD).
• develop a Swedish version of COMFORT-neo that is valid and culturally adapted
• validate ALPS-Neo against behavioural and biomedical pain markers (Comfort-neo, GSR and S-cortisol)
• determine whether specific pharmacogenetic (PG) profile explains the PK and PD phenotypes of these drugs in newborn infants (PK/PD/PG).
•collect descreptive data from neurological and cognitive follow-up examination at the age of 2 years . |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Term infants who, according to national guidelines, will receive hypothermic treatment following perinatal asphyxia, and are in need for analgesic or sedative medication according to clinical judgment based on Thomsons score and ALPS-Neo.
•Existing arterial or venous cannulas/catheters for repeated non-traumatic blood sampling
•Informed and written parental consent;
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E.4 | Principal exclusion criteria |
•AV- block I-III or HR < 70 – same as for hypothermia.
•Serious CHD with need for postnatal surgery – same as for hypothermia
•MABP <35 mmHg despite adequate treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change in drug concentration (metabolism) related to body temperature
• Effect of other medicines on clerance (including but not limited to phenobarbitone, midazolam, thiopentone).
• Change in neurophysiology response in relation to PK |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pre, during 72 h of hypothermic treatment until 72 h after normothermia is achieved. |
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E.5.2 | Secondary end point(s) |
•Change in/association between physiological parameters (heart rate (HR), mean arterial blood pressure (MABP, recorded invasively and, peripheral oxygen saturation (SpO2)) in relation to PK and other PD parameters.
•Change in/association between pain responses as measured by pain assessment score for continuous pain/stress (ALPS-Neo and Comfort Neo) and GSR, in relation to PK and other PD.
•Pain response as measured by pain assessment score ALPS-Neo and Comfort Neo in relation to GSR (=galvanic skin respons)
•Change in S-Cortisol in relation to PK and PD and pain response at a standardized pain procedure performed at a stage of stability after 6 hours of unchanged medication,
•How PK/PD phenotypes depend on pharmacogenetic (PG) profiles.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pre, during 72 h of hypothermic treatment until 72 h after normothermia is achieved. |
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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 | No |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Investigation on new patient group, infants during hypothermia |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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
| 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 | 2 |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |