E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory distress in neonates born at 34 to 38+6 weeks of gestation |
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E.1.1.1 | Medical condition in easily understood language |
Breathing problems in infants born 2-6 weeks early |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
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 compare duration of neonatal hospital stay in infants randomised to receive early surfactant versus those who received expectant management (standard hospital care).
To compare incidence of severe respiratory failure in infants randomised to receive early surfactant therapy versus those who received expectant management.
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E.2.2 | Secondary objectives of the trial |
To investigate the effects of early surfactant therapy with expectant management on perinatal (mother and baby) secondary outcomes.
To investigate the cost-effectiveness of early surfactant therapy with expectant management.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Born at 34+0–38+6 weeks of gestation 2. ≤ 24 hours old 3. Respiratory distress defined as: -FiO2 ≥ 0.3 and < 0.45 needed to maintain SaO2 ≥ 92%, or -Clinically significant work of breathing, regardless of FiO2 4. Clinical decision to provide non-invasive respiratory support 5. Written parental informed consent
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E.4 | Principal exclusion criteria |
1. Major structural or chromosomal abnormality 2. No realistic prospect of survival 3. Prior intubation and/or surfactant administration 4. Known or suspected hypoxic ischaemic encephalopathy 5. Congenital abnormality of the upper or lower respiratory tract 6. Known or suspected neuromuscular disorder
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E.5 End points |
E.5.1 | Primary end point(s) |
PRIMARY OUTCOMES • Length of infant’s hospital stay after birth, defined as the number of days from birth to discharge home from hospital • Incidence of severe respiratory failure, defined as: -sustained (≥ 30 minutes) requirement for FiO2 ≥ 0.45 to maintain oxygen saturations (SaO2) ≥ 92%
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Length of infant’s hospital stay will be evaluated between birth and discharge home from hospital. Incidence of severe respiratory failure will be evaluated between trial entry and discharge home from hospital. |
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E.5.2 | Secondary end point(s) |
PERINATAL CLINICAL OUTCOMES • Total duration of neonatal unit stay defined as total number of days of inpatient care in a neonatal unit (defined according to Healthcare Resource Group (HRG) Critical Care categories 1–5, 2016) • Total duration of neonatal intensive care support (defined according to HRG Critical Care categories 1-5, 2016) • Duration of mechanical ventilation (via endotracheal tube) • Duration of non-invasive respiratory support using positive airway pressure or high flow • Pulmonary air leaks requiring insertion of a chest drain • Days of mother-infant separation, defined using HRG Critical Care categories 1–5, 2016 • Breast milk feeding (any breast milk feeding during neonatal hospital stay; any breast milk feeding at hospital discharge and exclusive breast milk feeding at hospital discharge) • Late onset sepsis (microbiologically-confirmed or clinically suspected invasive infection more than 72 hours after birth) • Need for inhaled nitric oxide (iNO) therapy • Need for extra-corporeal membrane oxygenation (ECMO) • Medical respiratory diagnoses, defined as any respiratory diagnosis attributed to the infant • Surfactant administration • Maternal length of hospitalisation, defined as the total number of days spent by the mother in hospital after trial entry HEALTH ECONOMICS • Cost of maternal hospitalisation • Self-reported maternal health-related quality of life • Costs associated with neonatal care • Survival, paediatric secondary care use and associated costs using routine national databases such as Hospital Episode Statistics (HES) data
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary outcomes will be evaluated between trial entry and infant discharge home from hospital. The only exceptions are maternal length of hospitalisation, which will be evaluated between trial entry and maternal discharge home from hospital and paediatric secondary care use and associated costs, which will be evaluated between infant discharge home and one year of age, corrected for prematurity. |
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 |
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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 | 35 |
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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The end of trial will be defined as the point when the trial database is locked. An End of Trial Declaration will be made to the Medicines and Healthcare products Regulatory Agency (MHRA) and approving Research Ethics Committee (REC) within 90 days of the end of study. HES data will be requested from NHS Digital six months prior to the end of recruitment, and the timeframe and provision of these data will depend on NHS Digital response. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 30 |