E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Trauma |
Traumatisme grave [Injury Severity Score > 15]
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E.1.1.1 | Medical condition in easily understood language |
Multiple Trauma |
Traumatisme grave |
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E.1.1.2 | Therapeutic area | Not possible to specify |
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 demonstrate the efficacy of early intratracheal administration of dornase alfa in reducing the incidence of moderate and severe acute respiratory distress syndrome (PaO2/FiO2 ratio < 200) during the first 7 days post-traumatic in patients with severe trauma (ISS>15) and hospitalized in intensive care. |
Démontrer l’efficacité de l’administration intratrachéale précoce de dornase alfa pour réduire l’incidence du syndrome de détresse respiratoire aigu modéré et sévère (rapport PaO2/FiO2 < 200) au cours des 7 premiers jours post-traumatiques chez les patients victimes de traumatismes graves (ISS>15) et hospitalisés en réanimation. |
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E.2.2 | Secondary objectives of the trial |
Demonstrate the efficacy of early intratracheal administration of dornase alfa to reduce: the incidence of ventilation acquired pneumonia the impact of multi organ failure The incidence of minimal respiratory distress syndromes (200 < PaO2/FiO2 ≤ 300) the duration of mechanical ventilation (hours) the length of intensive care unit stay (hours) the length of hospital stay the mortality on D30
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Démontrer l’efficacité de l’administration intratrachéale précoce de dornase alfa pour réduire : • l’incidence des pneumopathies acquises sous ventilation mécanique • l’incidence de la défaillance multiviscérale o L’incidence des syndromes de détresse respiratoire minime (200 < PaO2/FiO2 ≤ 300) • la durée de ventilation mécanique post-traumatique • la durée de séjour en réanimation • la durée de séjour à l’hôpital • la mortalité à J30
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult (>18) patient of either sex affiliated to the National Health Service • Severe trauma patient (either blunt or penetrating), Injury Severity Score > 15 • Under mechanical ventilation for an expected duration > 48h • Admitted in the ICU for less than 6 hours (or less than 18 hours after arrival at the hospital[de-shocking] in the case of prior surgery or embolization) • Signed informed consent from the patient’s relative • Patient equipped with an indwelling arterial catheter |
- Patient majeur - Sujet affilié à un régime de protection sociale d’assurance maladie - Personne de confiance ayant été informée des résultats de la visite médicale préalable - Patient victime d’un traumatisme grave [Injury Severity Score > 15] - Patient admis en réanimation depuis moins de 6h (ou moins de 18h après l’arrivée à l’hôpital [déchocage] en cas d’interventions chirurgicales ou embolisation préalables) - Patient intubé dont la durée prévisible de ventilation mécanique est > 48h - Porteur d’un cathéter artériel
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E.4 | Principal exclusion criteria |
• Pregnancy or breast feeding • Opposition from the patient or his/her relatives • Protected major (Guardianship) • Contraindication to the use of dornase alfa • Known intolerance to dornase alfa • Ventilation by high frequency oscillations |
- Opposition du patient ou de la personne de confiance - Patiente enceinte (test de grossesse sanguin positif) - Patient sous mesure de tutelle ou sauvegarde de justice - Hypersensibilité connue à la dornase alfa ou à l’un des excipients - Traitement (en cours ou antérieur) par dornase alfa - Ventilation par oscillations à haute fréquence
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of moderate to severe ARDS (PaO2/FiO2 < 200, according to the Berlin definition in severe trauma patients (Injury Severity Score > 15). |
Incidence du syndrome de détresse respiratoire aigue (SDRA) modéré et sévère selon la classification de Berlin (rapport PaO2/FiO2 < 200) au cours des 7 premiers jours post-traumatiques chez les patients victimes de traumatismes graves (ISS>15) et hospitalisés en réanimation. |
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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- Incidence of VAP (ATS and CDC definitions) according to both the ATS and CDC definitions. 2- Incidence of multi-organ failure 3- Duration of mechanical ventilation [hours] 4- Length of ICU stay [hours] 5- Length of stay in the hospital 6- Mortality on day 30 7-- Incidence of minimal ARDS with a PaO2/FiO2 ratio between 200 and 300 |
1- Incidence des pneumopathies acquises sous ventilation mécanique [%] selon les définitions de l’American Thoracic Society (ATS et du Center for Disease Control and Prevention au cours des 7 premiers jours post-traumatiques. 2- Incidence de la défaillance multiviscérale [%] (selon le SOFA score au cours des 7 premiers jours post-traumatiques. 3-Durée de ventilation mécanique post-traumatique [en heures] entre l’intubation et la première extubation réussie (définie par l’absence de recours à la ventilation invasive pendant les 48h qui suivent l’extubation) 4- La durée de séjour en réanimation [en heures] 5- La durée de séjour à l’hôpital [en jours] 6- La mortalité à J30 7-L’ncidence du syndrome de détresse respiratoire minime avec un rapport PaO2/FiO2 compris entre 200 et 300 [200 < PaO2/FiO2 ≤ 300] |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- day 7 2- day 7 3- day 7 4- day 7 5- day 7 6. day 30 7- day 7 |
1- A 7 jours 2- A 7 jours 3- A 7 jours 4- A 7 jours 5- A 7 jours 6. A 30 jours 7- A 7 jours |
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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 | 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 | 7 |
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 | No |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |