E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Distress Syndrome in Premature Babies. |
respiratory distress syndroom (RDS) bij premature pasgeborenen. |
|
E.1.1.1 | Medical condition in easily understood language |
Premature baby immature lung disease. |
Te vroeggeboren kinderen met onrijpe longen |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 evaluate in a randomised controlled trial the efficacy of surfactant delivery via a minimally invasive technique in preterm infants 25-28 weeks gestation with RDS treated with CPAP. |
Het bepalen van het effect van de toediening van surfactant via een minimaal invassieve techniek bij premature kinderen (zwangerschapsduur 25-28 weken) aan de CPAP op hun overleving, respiratoire en neurologische uitkomst. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate that early surfactant administration via a minimally-invasive technique to preterm infants on CPAP will result in a lesser duration of mechanical respiratory support, and a higher incidence of survival without bronchopulmonary dysplasia. |
Het bepalen van het effect van de toediening van surfactant via een minimale techniek bij premature kinderen aan de CPAP op de beademingsduur en overleving zonder chronische longziekte. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Requiring CPAP or nasal IPPV because of respiratory distress.
2. CPAP pressure of 5-8 cm H2O and FiO2 ≥0.30.
3. Less than 6 hours of age.
4. Agreement of the Treating Physician in charge of the infant’s care.
5. Signed parental consent.
|
1. Preterme neonaten geboren na een zwangerschapsduur van 25-28 weken
2. CPAP of nasale intermitterende Positieve Druk Beademing vanwege RDS.
3. CPAP druk tussen 5 en 8 cm H2O en een FiO2 ≥ 0.30.
4. Minder dan 6 uur postnataal.
5. Toestemming van de behandelend arts.
6. Getekend informed consent van de ouders/verzorgers. |
|
E.4 | Principal exclusion criteria |
1. Previously intubated, or in imminent need of intubation because of respiratory distress, apnoea or persistent acidosis.
2. Congenital anomaly or condition that might adversely affect breathing.
3. Identifiable alternative cause for respiratory distress (e.g. congenital pneumonia or pulmonary hypoplasia).
4. Lack of availability of an OPTIMIST treatment team.
|
1. Geintubeerde neonaten, of wanneer intubatie nodig is vanwege de kliniek (respiratoire insufficientie, apnoes, onbehandelbare acidose)
2. Congenitale afwijking of stoornis die de ademhaling negatief beinvloedt.
3. Een alternatieve oorzaak voor de respiratoire problemen (congenitale pneumonie or longhypoplasie).
4. Het niet beschikbaar zijn van een OPTIMIST behandel team. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of composite outcome of death or physiological BPD |
Incidentie van een samengestelde uitkomstmaat: overlijden of bronchopulmonale dysplasie (BPD). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
36 week gestational age |
OP de leeftijd van 36 weken. |
|
E.5.2 | Secondary end point(s) |
• Physiological BPD
• Clinical BPD (requirement for oxygen or any form of positive pressure support at 36
weeks corrected gestation).
• Mild/moderate/severe BPD
• Death
• Death or BPD (clinical definition)
• Intraventricular haemorrhage (IVH) (all grades)
• IVH grades III and IV
• Periventricular leukomalacia
• Retinopathy of prematurity > stage II
• Major morbidity (any of IVH grade III or IV, periventricular leukomalacia, ROP >stage II, physiological BPD)
• Death or major morbidity
• NEC (Modified Bell stage 2 or greater)
• NEC or spontaneous intestinal perforation requiring surgery
• Requirement for intubation in the first 72 hours of life
• Requirement for intubation at any time
• Need for additional surfactant therapy
• Overall number of surfactant doses (including that given by MIST)
• Duration of intubation (all episodes)
• Duration of CPAP/NIPPV (all episodes)
• Duration of intubation and CPAP
• Duration of high flow nasal cannula (HFNC), minimum flow rate 2 L/min
• Duration of respiratory support
• Duration of oxygen therapy
• Requirement for oxygen at home
• Length of stay in intensive care
• Length of hospital stay
• Total hospital billings
• Calculated cost of hospitalisation
• Pneumothorax requiring drainage
• Pulmonary haemorrhage
• Patent ductus arteriosus (PDA) requiring anti-prostaglandin therapy
• PDA requiring ligation
• Late onset sepsis (positive bacterial or fungal culture from a normally sterile site)
• Time to regain birth weight
• Incidence of successful surfactant administration via MIST
• Number of catheterisation attempts
• Duration of bradycardia and hypoxaemia
• Requirement for, and duration of, positive pressure ventilation by mask
• Incidence of apparent discomfort
|
Secundaire uitkomsten: Incidentie van overlijden, ernstige neonatale morbiditeit (BPD, intraventriculaire bloeding, periventriculaire leukomalacie, retinopathie van de prematuur, necrotiserende enterocolitis, pneumothorax en open ductus arteriosus; noodzaak voor intubatie en surfactant therapie; duur van intubaties, van mechanische ventilatie, van CPAP, van intubatie en CPAP, van high flow nasale canule, van zuurstof therapie, van opnameduur intensive care en verpleegafdeling; hospitalisatie kosten; uitvoerbaarheid en veiligheid van de MIST procedure; en lange termijn (neurologische) uitkomst op de leeftijd van 2 jaar. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Discharge of baby from hospital (first admission) |
Onslag van het kind naar ander zieken huis. De lange termijn (neurologische) uitkomst op de leeftijd van 2 jaar. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Een sham procedure zal worden uitgevoerd |
A sham procedure will be performed. |
|
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 | 1 |
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 | Yes |
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 |
Australia |
Israel |
Netherlands |
New Zealand |
Slovenia |
Turkey |
United States |
|
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |