Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS

ARDS Clinical Trial

Official title:

Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS - a Randomised, Placebo-controlled, Double-blind Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03567577
• Other study ID #: AP301-II-002
• Status: Recruiting
• Phase: Phase 2
• Start date: May 23, 2018
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: Apeptico Forschung und Entwicklung GmbH
• Contact: Bernhard Fischer, Prof. Dr.
• Phone: 0043-664143
• Email: b.fischer[@]apeptico.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase IIb, randomized, placebo-controlled, double-blind, dose escalation study will 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 and review potential efficacy endpoints for a future phase III pivotal trial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 95
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Informed consent

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 in Appendix I) and stable in this condition for at least 8 hours.

4. Moderate-to-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. ARDS diagnosis 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.

8. For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.

9. Male and Female (WOCBP) patients using adequate contraception.

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 enrolment.

3. Severe state of septic shock with a Mean Arterial Pressure (MAP) = 65 mm Hg and a 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. In no way are patients to be denied or delayed these procedures to avoid exclusion from the study.

6. Neutrophil count < 0.3 x 109/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 oedema diagnosed by echocardiography or pulmonary artery catheter.

10. Severe 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.

Related Conditions & MeSH terms

• ARDS

Intervention

Drug:
• Solnatide 25 mg powder for reconstitution for solution for inhalation
Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.
• 0.9% Saline Solution
Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.

Locations

Country	Name	City	State
Austria	Univ.-klinik f. Herz-, Thorax-, Gefäßchirurgische Anästhesiologie und lntensivmedizin, Medizinische Universität Graz	Graz	Steiermark
Austria	Univ. Klinik für Innere Medizin / Gem. Einrichtung für Intensiv- und Notfallmedizin/GE Medizinische Universität Innsbruck	Innsbruck
Austria	Department of Anesthesia, General Intensive Care and Pain Control,Medical University of Vienna	Vienna
Germany	Klinik für Operative Intensivmedizin und Intermediate Care	Aachen	Nordrhein-Westfalen
Germany	Universitätsklinikum Bonn, Operative Intensivmedizin, Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin	Bonn
Germany	Klinik und Poliklinik für Anästhesiologie und Intensivtherapie / Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen
Germany	Georg-August-Universität Göttingen	Göttingen
Germany	Klinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Schleswig-Holstein, Campus Kiel,	Kiel
Germany	Klinik für Anästhesiologie / Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Klinik für Anästhesiologie und operative Intensivmedizin; Universitätsmedizin Mannheim	Mannheim
Germany	Klinik für Anaesthesiologie, Klinikum der Universität München, Campus Großhadern	München	Bayern
Germany	Klinik für Anästhesiologie und Intensivmedizin; Klinikum rechts der Isar der TU München	München
Germany	Klinik und Poliklinik für Innere Medizin II; Klinikum rechts der Isar der TU München	München
Germany	Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie; Universitätsklinikum Münster	Münster
Germany	Universitätsklinikum Würzburg, Klinik und Poliklinik für Anästhesiologie	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
Apeptico Forschung und Entwicklung GmbH

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety endpoint: Any cause death	Primary Safety Endpoint: Composite endpoint including any cause death at day 28	Randomisation - day 28
Primary	Safety endpoint: Drug-related adverse events	Primary Safety Endpoint: Composite endpoint including drug-related adverse events through day 14	Randomisation - day 14
Primary	Safety endpoint: All adverse events	Primary Safety Endpoint: Composite endpoint including all adverse events through day 28	Randomisation - day 28
Secondary	EVLWI	Change in extravascular lung water index (EVLWI) as assessed with a validated bedside measurement (measurement with the PiCCO® system)	baseline - day 7
Secondary	PVPI	Change in pulmonary vascular permeability index (PVPI) as assessed with a validated bedside measurement (measurement with the PiCCO® system)	baseline - day 7
Secondary	Change of ventilatory settings	Composite endpoint including ventilation mode, ventilation pressures (ventilatory plateau pressure, positive end expiratory pressure, peak inspiratory pressure, mean airway pressure, peak airway pressure, driving pressure), tidal volume	baseline - day 14
Secondary	Murray lung injury score	Murray lung injury score is composed of four components: 1) chest radiograph; 2) hypoxaemia score; 3) PEEP and 4) static compliance of respiratory system. The values of the total score may range from 0 to 4. Lower values indicate a better outcome.	baseline - day 7
Secondary	Oxygenation ratio (PaO2 / FiO2 ratio)		baseline - day 7
Secondary	Time to extubation		baseline - day 28
Secondary	Ventilator-free days (VFD)		baseline - day 28
Secondary	Days of hospitalization and in ICU		baseline - day 28