E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Preterm Infants at risk of respiratory distress syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Premature babies at risk of respiratory distress syndrome |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10054933 |
E.1.2 | Term | Neonatal respiratory distress syndrome prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
Our primary objective is to investigate the efficacy of prophylactic oropharyngeal surfactant for reducing the rate of endotracheal intubation, compared to no intervention in infants at risk of RDS. |
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E.2.2 | Secondary objectives of the trial |
To investigate the efficacy of prophylactic oropharyngeal surfactant compared to no intervention for preventing some possible complications in premature infants at risk of RDS, we will also record a number of variables relating to prematurity, from enrolment into the trial until discharge home from hospital. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• born at a participating centres with a gestational age at birth < 29 weeks (i.e. up to 28+6 days gestation) by best obstetric estimate; and
• the treating doctors plan to offer them intensive care
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E.4 | Principal exclusion criteria |
- Infants with major congenital anomalies including neural tube defects, major structural cardiac anomalies (excluding PDA/ASD/VSD), abdominal wall defects and congenital diaphragmatic hernia and major dysmorphic features with an abnormal karyotype e.g. T21, T13, T18
- The treating clinician does not intend to offer the infant intensive care.
- Written informed consent has not been obtained prior to delivery or subjects’ parent(s)/guardian(s) withdraws consent following enrolment.
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E.5 End points |
E.5.1 | Primary end point(s) |
The incidence of endotracheal intubation for respiratory failure within 120 hours of birth. Enrolled infants will be intubated for persistent apnoea and/or bradycardia in the DR, or for respiratory failure in the NICU defined as ≥ 2 of:
• Clinical signs – worsening tachypnoea; grunting; subcostal, intercostal and/or sternal recession
• Acidosis – pH < 7.2 on 2 blood gases (arterial or capillary) ≥ 30 minutes apart
• O2 – FiO2 > 0.4 to keep SpO2 ≥ 90% for > 30 minutes
• PCO2 > 9.0 kPa on 2 blood gases (arterial or capillary) ≥ 30 minutes apart
• Apnoea – recurrent apnoea treated with mask ventilation
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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) |
1. Number of attempts taken to successfully intubate in the DR
2. Chest compressions in the DR
3. Adrenaline administration in the DR
4. Rectal temperature on admission to the NICU
5. NICU intubation
6. Surfactant use before death or hospital discharge
7. Number of doses, including total dose
8. Intra-tracheal surfactant received post-intervention
9. Doses of post-intervention surfactant
10. Respiratory distress syndrome
o Clinical evidence of respiratory distress with radiological evidence (ground glass appearance on CXR)
11. Incidence of pneumothorax
o Incidence of pneumothorax on CXR
12. Incidence of pulmonary haemorrhage
o Clinical evidence of pulmonary haemorrhage
13. Mechanical ventilation
14. Days of mechanical ventilation
15. Use of postnatal corticosteroids for ventilator dependence
16. Days of duration of respiratory support (endotracheal ventilation, high-frequency oscillatory ventilation, CPAP, heated humidified high-flow nasal cannula O2 ,low flow nasal cannula O2)
17. Bronchopulmonary dysplasia (BPD) –supplemental O2 at 28 days of life
18. Chronic lung disease of prematurity (CLD) – need for supplemental O2 at 36 weeks corrected gestational age (CGA) determined by physiological oxygen reduction test
19. Medical treatment for a patent ductus arteriosus
o Administration of ibuprofen or paracetemol for PDA
20 Surgical treatment for a patent ductus arteriosus
21. Proven necrotising enterocolitis (≥ Bell’s stage 2)
22. Incidence of Intraventricular haemorrhage (IVH) (any and severe: IVH grade ≥ 3)
o Evidence on surveillance cranial ultrasounds performed regularly in NICU as standard of care
23. Incidence of cystic periventricular leukomalacia
o Evidence on surveillance cranial ultrasounds performed regularly in NICU as standard of care
24. Retinopathy of prematurity treated with laser photocoagulation or intravitreal injections
o Evidence on surveillance ophthalmology review performed regularly in NICU as standard of care
25. Death before hospital discharge
26. Survival without BPD at hospital discharge
27. Survival without CLD at hospital discharge
28. Duration of hospitalisation
29. Use of home oxygen therapy
o Discharged home on oxygen therapy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Endpoints 1-5 will be measured between day 0 - 120 hours of life.
Secondary Endpoint 17, Bronchopulmonary dysplasia will be assessed at 28 days of life.
Secondary Endpoint 18, Chronic lung disease prematurity, will be assessed at 36 weeks corrected gestational age.
All remaining secondary endpoints to be assessed at discharge home.
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Continuous positive airway pressure (CPAP) as per routine practice |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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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LVLS (discharge of patient) |
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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 | |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |