pulmonary permeability oedema in patients with moderate-to-severe ARDS MedDRA version: 21.1 Level: LLT Classification code 10003083 Term: ARDS System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 20.0 Level: PT Classification code 10037423 Term: Pulmonary oedema System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Solnatide
Pharmaceutical Form: Powder for nebuliser solution
CAS Number: 259206-53-06
Current Sponsor code: AP301
Other descriptive name: human tumour necrosis factor alpha-derived pepti
Sponsors
Apeptico Forschung und Entwicklung GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study will enrol patients with pulmonary permeability oedema (EVLWI = 10) and moderate to severe ARDS admitted to an Intensive Care Unit (ICU) and under mechanical ventilation*. To be eligible to participate in this study, an individual must meet all the following criteria: 1. Informed consent (for details see Section 10.1.1) 2. Male or female =18 years of age 3. Patient has been admitted to an ICU, is mechanically ventilated (according to the ventilation and weaning protocol as outlined in the study protocol) and stable in this condition for at least 8 hours 4. Moderate and severe ARDS diagnosis as defined by the Berlin Definition: • Onset of ARDS within 1 week of a known clinical insult or new or worsening respiratory symptoms • Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules • Respiratory failure not fully explained by cardiac failure or fluid overload (origin of oedema) • PaO2/FiO2 = 200 mm Hg with Positive End-Expiratory Pressure (PEEP) =5 cm H2O 5. Verified ARDS diagnosis (moderate or sever according to BERLIN Definition) not older than 48 hours 6. Extravascular lung water index (EVLWI) = 10 mL/PBW, as assessed with a validated bedside measurement (single indicator transpulmonary thermodilution measurement with the PiCCO system) 7. Patient who meets criteria for extensive hemodynamic monitoring as per international intensive-care medicine standards Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. History of clinically relevant allergies or idiosyncrasies to solnatide 2. Known use of any other investigational or non-registered drug within 30 days prior to study enrollment 3. Severe state of septic shock with a Mean Arterial Pressure (MAP) = 65 mm Hg and serum lactate level > 4 mmol/L (36 mg/dL) despite adequate volume resuscitation 4. An underlying clinical condition that, in the opinion of the Investigator, would make it very unlikely for the patient to be successfully weaned from ventilation due to severe underlying diseases (e.g. severe malnutrition, severe neurological diseases, pulmonary fibrosis or COPD) 5. Extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support 6. Neutrophil count < 0.3 x 10^9/L 7. Cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks 8. Cachexia (BMI < 18.5 kg/m2) 9. Cardiogenic pulmonary edema diagnosed by echocardiography or pulmonary artery catheter 10. Skin burns involving more than 15% of body surface 11. Subjects who are extremely unlikely to survive more than 48 hours due to the acute conditions of the patient in the opinion of the Investigator 12. Subjects transferred from a hospital not participating in this study who are already planned to be re-transferred during the observation period 13. Subjects who are not expected to survive the next month because of an underlying uncorrectable medical condition or a do not resuscitate order 14. Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the local and systemic safety of 7 days orally inhaled sequential multiple ascending doses of solnatide in patients with pulmonary permeability oedema and moderate-to-severe ARDS.;Secondary Objective: To review potential efficacy endpoints for a future phase III pivotal trial. To assess plasma level of orally inhaled solnatide in selected patients.;Primary end point(s): Safety Safety will be assessed by a review of mortality, the incidence of adverse events and serious adverse events, as well as by analysis of relevant laboratory data and ECG. Safety parameters •Drug-related adverse events (through day 14) •All adverse events through day 28 •All-cause deaths through day 28 •Vital signs daily through day 14 (heart rate, systolic and diastolic blood pressure, and body temperature) •ECG parameters including heart rate PQ, QRS, QT and QTc intervals through day 7 •Clinical laboratory assessments (haematology, clinical chemistry, blood gases and urine analysis) daily through day 14 •24-hour fluid balance through day 7 •Hemodynamic parameters: mean arterial pressure, pulmonary blood volume (PBV), cardiac index and cardiac output assessed at screening and daily until end of treatment •Need for vasoactive drugs assessed at screening and daily until end of treatment Preliminary efficacy parameters •Change from baseline to day 7 in EVLWI and pulmonary vascular permeability index (PVPI) as assessed with a validated bedside measurement (single indicator transpulmonary thermodilution measurement with the PiCCO system) •Lung compliance through day 14, if patient is mechanical ventilated (controlled mechanical ventilation) •Murray lung injury score (LIS) through day 7 if chest x-ray is available •Oxygenation ratio (PaO2/FiO2 ratio) assessed through day 7 •Ventilation parameters: ventilatory plateau pressure, tidal volume (Vt), positive end expiratory pressure (PEEP), respiratory rate, FiO2, peak inspiratory pressure (PIP), mean airway pressure, peak airwa | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): not applicable;Timepoint(s) of evaluation of this end point: n.a. | — |
Countries
Austria, Germany
Contacts
Public ContactProf. Dr. Bernhard Fischer
Apeptico Forschung und Entwicklung GmbH
Outcome results
None listed