E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypoperfusion status of preterm and term newborns during the first days of life. |
Hüpoperfusioon enneaegsetel ja ajalistel vastsündinutel esimestel elupäevadel. |
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E.1.1.1 | Medical condition in easily understood language |
Low blood flow status of very sick preterm and term newborns during the first days of life. |
Väga haigete enneaegsete ja ajaliste vastsündinute vereringe puudulikkus esimestel elupäevadel. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 describe the pharmacokinetics and pharmacodynamics of dobutamine in preterm and term neonates during the first days of life. |
Kirjeldada dobutamiini farmakokineetikat ja farmakodünaamikat enneaegsetel ja ajalistel vastsündinutel esimestel elupäevadel. |
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E.2.2 | Secondary objectives of the trial |
To find out the optimum dose of dobutamine in relation to organ perfusion in neonates and to assess the safety profile of dobutamine in preterm and term neonates during the first days of life.
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Leida optimaalne dobutamiini doos sõltuvalt soovitud südame- ja veresoonkonna efektist ja hinnata dobutamiini ohutust enneaegsetel ja ajalistel vastsündinutel esimestel elupäevadel.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Postnatal age below 72 hours 2) Need for inotropic therapy (based on clinical and biochemical data) 3) Informed consent given by the parents or guardians 4) Arterial catheter and/or central venous catheter in place on clinical indication
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1) Postnataalne vanus kuni 72 tundi 2) Inotroopne ravi dobutamiiniga on lapse seisundist tulenevalt vajalik 3) Vanemate või seadusliku esindaja kirjalik teavitatud nõusolek uuringus osalemiseks 4) Arteri- ja/või tsentraalveeni kanüül on paigaldatud kliinilisel näidustusel
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E.4 | Principal exclusion criteria |
1) Congenital defect that impacts haemodynamics /response to inotropic therapy (congenital heart disease) 2) Congenital hydrops 3) Other unresolved cause of low blood flow (air leak) 4) Known metabolic disease 5) Informed consent from parents or guardians not obtained 6) Situation where the treating physician considers a different vasoactive treatment necessary/dobutamine contraindicated 7) Hypersensitivity to dobutamine or any other component of the study drug
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1) Kaasasündinud väärareng, mis mõjutab oluliselt vereringet/ vastust inotroopsetele ravimitele (näiteks südamerike) 2) Kaasasündinud hüdrops 3) Teadaolev lahendamata madala verevoolu põhjus (pneumotooraks) 4) Teadaolev ainevahetushaigus 5) Puudub vanemate või seadusliku esindaja teavitatud nõusolek uuringus osalemiseks 6) Olukord, kus raviarst otsustab mõne muu inotroopse ravimi kasuks või dobutamiin on vastunäidustatud 7) Ülitundlikkus uuritava ravimi ja/või mõne selle abiaine suhtes
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E.5 End points |
E.5.1 | Primary end point(s) |
The pharmacokinetics of dobutamine in preterm and term neonates. Adverse events experienced by neonates receiving dobutamine.
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Dobutamiini farmakokineetika enneaegsetel ja ajalistel vastsündinutel. Dobutamiini ebasoodsad toimed vastsündinutel. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetic parameters are evaluated during the treatment period and 15 min after the end of treatment with dobutamine. Adverse events are recorded until 24 hours after the end of treatment with dobutamine. |
Farmakokineetikat hinnatakse dobutamiinravi ajal ja 15 minutit peale ravimi infusiooni lõpetamist. Ebasoodsaid toimeid registreeritakse kuni 24 tundi peale dobutamiini infusiooni lõpetamist. |
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E.5.2 | Secondary end point(s) |
Pharmacodynamics of dobutamine, including effects on blood pressure, heart rate and percutaneous oxygen saturation, central haemodynamics assessed by heart ultrasonography, regional cerebral perfusion assessed by NIRS and microcirculation, assessed by SDF imaging in neonates during first days of life.
Clinical and biochemical measures of systemic hypoperfusion, including blood gases, lactate, diuresis.
Clinical outcome at FU visit – survival, duration of respiratory and vasoactive support.
Neurological evaluation as assessed by cerebral ultrasound at any time up until the FU visit.
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Dobutamiini faramakodünaamika: toime vererõhule, südamesagedusele, hapnikusaturatsioonile, tsentraalse hemodünaamika parameetritele (hinnatakse südame ultraheliuuringul), aju regionaalsele verevoolule(hinnatakse NIRS monitooringuga) ja naha mikrotsirkulatsioonile (hinnatakse videokapillaroskoopial).
Süsteemse hüpoperfusiooni kliinilised ja biokeemilised tunnused - veregaasid, laktaat, diurees.
Kliiniline tulem FU visiidil - elulemus, hingamis- ja vereringetoetuse kestus.
Neuroloogiline hindamine aju ultraheli uuringul kuni FU visiidini.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The pharmacodynamic effect of dobutamine is evaluated during the treatment/intervention period (starts from the beginning of treatment with IMP and ends 30 min after the dobutamine dose escalation to the highest level of 15 or 20 μg/kg/min) , haemodynamic parameters are recorded continuously or 20-30 min after each dose escalation (heart ultrasonography and videocapillaroscopy).
Clinical and biochemical measures of hypoperfusion are taken at the end of treatment/intervention period.
FU visit is 24 hours after the end of treatment with dobutamine. |
Dobutamiini farmakodünaamilist toimet hinnatakse raviperioodi jooksul (algab dobutamiinravi algusest ja lõpeb 30 min peale dobutamiini doosi tõstmist maksimaalsele tasemele 15 või 20 μg/kg/min) , hemodünaamika parameetrid salvestatakse pidevalt või 20-30 min peale igat doosi tõstmist (südame ultraheliuuring ja videokapillaroskoopia).
Hüpoperfusiooni kliinilisi ja biokeemilisi tunnuseid hinnatakse raviperioodi lõpus.  FU visiit on 24 tundi peale ravi lõpetamist dobutamiiniga. |
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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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |