E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary permeability oedema in SARS-Cov-2 positive patients with moderate-to-severe ARDS |
Pulmonales Permeabilitätsödem bei SARS-Cov2 positiven Patienten mit mäßigem bis schwerem akutem Atemnotsyndrom (ARDS) |
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E.1.1.1 | Medical condition in easily understood language |
Pulmonary permeability oedema in SARS-Cov-2 positive patients with moderate-to-severe ARDS |
Pulmonales Permeabilitätsödem bei SARS-Cov2 positiven Patienten mit mäßigem bis schwerem akutem Atemnotsyndrom (ARDS) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003083 |
E.1.2 | Term | ARDS |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037423 |
E.1.2 | Term | Pulmonary oedema |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 |
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.
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E.2.2 | Secondary objectives of the trial |
• 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
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Full title: Biomarker Sub-Study by Prof. Schaden Version: 2.0 Date: 01.04.2020 Objective: -To assess the role of the coagulation system in the pathogenesis of COVID-19 -To assess the benefit of coagulation markers for the prognosis and course of disease in seriously ill COVID-19 patients -To find possible therapeutic targets |
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E.3 | Principal 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 < 200 mm Hg continuously observed for a period of ≥4hours (≥2 ABG analyses during that time, with the last value obtained shortly prior to randomization), minimum PEEP ≥8 cm H2O 6. Time from intubation to randomization ≤ 96h |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to day 7, respectively to day 14 or day 28. |
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E.5.2 | 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline to day 7, respectively to day 14, 28 or 60. |
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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 | 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 | 4 |
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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The end of the study is defined as completion of the last visit or procedure by all patients in 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 | |