E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024895 |
E.1.2 | Term | Low blood pressure |
E.1.2 | System Organ Class | 100000004866 |
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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 |
To determine whether in infants born before 28 completed weeks of gestation, an observational approach to the management of hypotension compared to a standard approach using dopamine as a first line inotrope within the first 72 hrs improves: 1. Survival free from neurodevelopmental disability at 2 years corrected gestational age (GA). 2. Survival without significant brain injury at 36 weeks corrected GA.
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E.2.2 | Secondary objectives of the trial |
To determine whether an observational approach to the management of hypotension compared to a standard approach with dopamine affects: •All cause mortality at 36 weeks GA. •The incidence of severe abnormality (grade III-IV intraventricular haemorrhage (IVH), periventricular cystic leukomalacia or ventricular dilatation) detected on serial cranial ultrasound examinations. •The number of adverse effects attributable to treatment. •Individual impairments at 2 years. •Developmental and behavioural scores at 2 years. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Gestational age from 23 weeks at birth to less than 28 completed weeks (i.e. up to and including 27 weeks and 6 days). •Within 72 hours of birth. •An indwelling arterial line, suitably calibrated and zeroed, to monitor blood pressure with the measuring dome at the level of the mid axillary line when supine. •A pre-trial cranial ultrasound scan free of grade III-IV IVH or cystic PVL. •A mean blood pressure (BP) 1 mmHg or more below a mean BP value equivalent to the GA in completed weeks, which persists over a 15 minute period.
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E.4 | Principal exclusion criteria |
•Infant is considered non-viable by attending clinicians. •Life-threatening congenital abnormalities including congenital heart disease (excluding patent ductus arteriosus) and chromosomal abnormalities. Infants known to require surgical treatment e.g. congenital diaphragmatic hernia, tracheoesophageal fistula, omphalocele, gastroschisis. Hydrops Fetalis. •Parenchymal haemorrhage or a grade III IVH (where over 50% of the ventricle is filled with blood).
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E.5 End points |
E.5.1 | Primary end point(s) |
Survival free from neurodisability at 2 years corrected GA.
Survival to 36 weeks corrected GA free of severe brain injury on 36 week cranial ultrasound.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Survival free from neurodisability at 2 years corrected gestational age
Survival to 36 weeks corrected GA free of severe brain injury on 36 week cranial ultrasound.
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E.5.2 | Secondary end point(s) |
All cause of mortality at 36 weeks corrected gestational age
All cause of mortality before first discharge home.
Recording and reporting of any Adverse Events.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
36 weeks corrected gestational age |
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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 | Yes |
E.6.8 | Bioequivalence | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Czech Republic |
Ireland |
United Kingdom |
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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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Neurological assessment at 24 months corrected GA. |
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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 | 5 |
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 | 5 |
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 |