E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Distress Syndrome of preterm babies born < 32 weeks of gestational age |
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E.1.1.1 | Medical condition in easily understood language |
Respiratory Distress Syndrome of preterm babies born < 32 weeks of gestational age |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
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 |
In a population of preterm babies less than <32wGA, our objective is to perform a double-blind, non-inferiority trial comparing sedation by Propofol versus placebo during the LISA procedure, evaluating the need for MV within 72hours of life. |
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E.2.2 | Secondary objectives of the trial |
1. To compare sedation by Propofol versus placebo during the LISA procedure, evaluating the need for MV within 72hours of life, in each class of GA (<28, 28-31wGA)
2. To assess comfort and reduction of pain in the intervention versus control group, during the LISA procedure and at 1 hour after it
3. To assess the rate of ketamine administration for rescue in each group
4. To assess the quality conditions of the procedure: per procedure events (tolerance) and the clinician’s satisfaction (efficacy) during the LISA procedure
5. To assess BPD at 36wGA
6. To assess in-hospital neonatal morbidity and mortality.
7. To evaluate the neurodevelopmental outcome at two years corrected age among survivors.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Preterm Infants < 32 wGA
- Presenting a RDS
in the first 48 hours of life
treated by CPAP
requiring surfactant :
FIO2 :
if 28 - 31 SA : FiO2 ≥30% for a duration ≥ 10mn
if <28 SA FIO2 ≥25% for a duration ≥10mn
SaO2 :
To obtain a SaO2 between ≥88 and ≤ 95%
- Available Intra-Venous line
- Covered by French Social Security
- Informed consent form signed
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E.4 | Principal exclusion criteria |
- Congenital and/or major malformations
- FIO2> 60%
- Silverman score> at 6
- Low Blood Pressure with 2 successive measurements (Mean < Gestational Age expressed in Weeks of Gestation) persisting after one volume expansion
- Use of inotropic medication to maintain normal blood pressure.
- Use of sedative or analgesic drugs (except paracetamol and ibuprofen) in the previous 24h
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of MV from the start of the LISA procedure up to 72 hours of life in each group.
The need of MV will be indicated by:
• Repeated and severe apnea with bradycardia and/or low oxygen saturation, according the American Academy of Pediatrics Guidelines (American Academy of Pediatrics, 2003):
o Respiratory pause during 20 sec
o Or a shorter respiratory pause if accompanied by bradycardia or cyanosis
• High FIO2 justifying intubation for a second administration of surfactant and mechanical ventilation
• Respiratory complications such pneumothorax, with an aggravation of the respiratory distress syndrome
• Any other cause where the clinician judges the necessity for mechanical ventilation: the motive for the respiratory assistance must be indicated in the case report form |
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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. Rate of MV from the start of the LISA procedure up to 72 hours of life in each class of GA (<28, 28-31wGA)
2. Faceless Acute Neonatal Scale (FANS) assessed during the LISA: this scale evaluates behavioral items (limb movements, vocal expression) and physiological items (heart rate variation, bradycardia or desaturation), on a scale from 0 (no pain) to 10 (maximal pain). Its reliability and validity have already been documented (Milesi, Arch Dis Child Fetal Neonatl Ed 2010). This scale allows a painful procedure to be evaluated, whether the face is visible or not.
3. Rate of ketamine administration for rescue: This administration will be indicated after two (< 28 wGA) or 3 (28 – 31 wGA) administrations of the drug, if adequate comfort is not achieved (FANS≥6) (See paragraph 5.3)
4. Quality conditions
5. BPD at 36 wGA according the definition proposed by Jobe with the distinction between severe, moderate and mild BPD (Jobe 2001)
Final Evaluation at a post-conceptional age of 36wGA
6. In-hospital neonatal morbidity and mortality
7. At two years : ASQ questionnaire, Gross Motor Function Classification Scale in cases of motor impairment, Visual and hearing function |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | 12 |
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 the study is the Follow up visit at two years. |
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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 | |
E.8.9.1 | In the Member State concerned days | |