E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of orally inhaled AP301 on alveolar liquid clearance in ALI patients with the purpose to assess the treatment associated changes of extravascular lung water (EVLW) within 7 days of treatment. |
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E.2.2 | Secondary objectives of the trial |
To assess: • the treatment associated changes of oxygenation as measured by the PaO2 / FiO2 ratio until day 7 of therapy, • the ventilatory plateau pressure and other ventilation parameters (Tidal volume, positive endexpiratory pressure, PIP, FiO2, respiratory rate, mean airway pressure and peak airway pressure) until day 7 of therapy, • the Murray lung injury score (a composite variable that includes components of oxygenation, compliance, positive end-expiratory pressure, and the appearance of the chest radiograph), • the duration of stay at ICU in the first 28 days, • the duration of controlled ventilation period until extubation, • number of days free from ventilatory support [for > 48 h] in the first 28 days • the survival status at day 28, • the local and systemic safety and tolerability and to identify possible dose related adverse events.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- age ≥ 18 - intubated and mechanically ventilated male and female patients of the Intensive Care Units of the Department of Anesthesia, General Intensive Care and Pain Control - meets the criteria of ALI (as defined by the American-European Consensus Conference on ALI/ ARDS): - Onset of ALI within 48 hours - Bilateral infiltrates seen on frontal chest radiograph - PCWP ≤ 18 mm Hg or no clinical evidence of left atrial hypertension - paO2/ FiO2 ratio ≤ 300 mm Hg
- EVLW in PiCCO® at screening ≥ 8 ml/PBW - Meeting criteria for extensive hemodynamic monitoring according to investigators discretion - Informed consent: - For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided. |
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E.4 | Principal exclusion criteria |
Medical Issues • History of clinically relevant allergies or idiosyncrasies to AP301 or any other inactive ingredient(s) of the investigational product • Brainstem death at screening • Current evidence of septic shock as defined by the Surviving Sepsis Campaign (Presence of acute organ dysfunction secondary to infection plus hypotension with systolic blood pressure < 90 mm Hg or mean arterial pressure (MAP) < 70 mm Hg for not less than one hour which cannot be reversed with fluid resuscitation) • Neutrophil count <0.3 x 10^9 L • Patients under immunosuppression: high dose steroids (> 80 mg Prednisolone /d; > 300 mg hydrocortisone / d), cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks • BMI < 18.5 or > 35 • Pregnancy / lactation or intention to fall pregnant during the time course of the study • Women of childbearing potential who are not using adequate contraception
General Issues • Participation in other interventional drug trials
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint is EVWL (measured with PiCCO® technique) between day 0 and day 7 of treatment. |
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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) |
• Oxygenation index (PaO2 / FiO2 ratio) until day 7 of treatment • Ventilator plateau pressure until day 7 of treatment • Murray Lung Injury Score until day 7 of treatment • Ventilation parameters / lung function: tidal volume (Vt), positive endexpiratory pressure (PEEP), PIP, respiratory rate, FiO2 , meak airway pressure, peak airway pressure until day 7 of treatment • Duration of stay at ICU in the first 28 days • Duration of controlled ventilation period until extubation • Number of days free from ventilation support (for > 48 h) in the first 28 days • Survival status at day 28 • the local and systemic safety and tolerability and to identify possible dose related adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline to day 7 respectively day 28 (+7) |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |