Pulmonary permeability oedema in SARS-Cov-2 positive 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 suspension
INN or Proposed INN: Solnatide
CAS Number: 259206-53-06
Current Sponsor code: AP301
Other descriptive name: human tumour ne
Sponsors
Department of Clinical Pharmacology, Medical University of Vienna, Vienna Austria
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study will enrol SARS-Cov-2 positive patients with 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, if possible. 2. Male or female =18 years of age. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen. 4. Patient has been admitted to an ICU, is mechanically ventilated (according to the ventilation and weaning protocol as outlined in Appendix I) and stable in this condition for at least 8 hours. 5. 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 =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. History of clinically relevant allergies or idiosyncrasies to solnatide. 2. 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. 3. 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). 4. Extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support. In no way are patients to be denied or delayed these procedures to avoid exclusion from the study. 5. Neutrophil count < 0.3 x 10^9/L. 6. 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. 7. Subjects who are not expected to survive the next month because of an underlying uncorrectable medical condition or a do not resuscitate order 8. Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment of the efficacy of 7 days orally inhaled 100 mg solnatide in Covid-19 patients with moderate-to-severe ARDS. Primary endpoint: • Days free of mechanical ventilation (ventilator free days, VFD) within 28 days. ;Secondary Objective: • Assessment on the effect of solnatide on the extravascular lung-water-index (EVLWI), if available • Hemodynamic parameters • Ordinal Scale for Clinical Improvement, as proposed by the WHO ;Primary end point(s): • Days free of mechanical ventilation (ventilator free days, VFD) within 28 days • 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 (if available) 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;Timepoint(s) of evaluation of this end point: Baseline to day 7, respectively to day 14 or day 28. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in ordinal Scale for Clinical Improvement, as proposed by the WHO (assessed daily until discharge; if early discharge at day 14 and 28 after randomization) • All-cause mortality (day 28 and day 60 after randomization) • If available, change from baseline to day 7 in extravascular lung water index (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 airway pressure, ventilation mode through day 14, if patient is mechanical ventilated (controlled mechanical ventilation, assisted breathing, non-invasive ventilation) • Driving pressure (Pplat - PEEP) through Day 14 • Spontaneous breathing trial • Time to extubation through day 28 • Days of hospitalization through day 28, defined as the difference between the date of discharge and the date of randomization. Days of outpatient hospitalization will not be included. • ICU days through day 28. ICU days is defined as the number of calendar days a patient was in the ICU until completion of day 28.;Timepoint(s) of evaluation of this end point: Baseline to day 7, respectively to day 14, 28 or 60. | — |
Countries
Austria
Contacts
Public ContactMarkus Zeitlinger
Department of Clinical Pharmacology, Medical University of Vienna, Vienna Austria
Outcome results
None listed