Clinical trial NCT03567577: Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: ARDS
Keywords: Peptide
Lead sponsor: Apeptico Forschung und Entwicklung GmbH
Sponsor class: INDUSTRY
First posted: 2018-06-26
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety endpoint: Any cause death
timeFrame: Randomisation - day 28
measure: Safety endpoint: Drug-related adverse events
timeFrame: Randomisation - day 14
measure: Safety endpoint: All adverse events
timeFrame: Randomisation - day 28
Secondary outcomes:
measure: EVLWI
timeFrame: baseline - day 7
measure: PVPI
timeFrame: baseline - day 7
measure: Change of ventilatory settings
timeFrame: baseline - day 14
measure: Murray lung injury score
timeFrame: baseline - day 7
measure: Oxygenation ratio (PaO2 / FiO2 ratio)
timeFrame: baseline - day 7
measure: Time to extubation
timeFrame: baseline - day 28
measure: Ventilator-free days (VFD)
timeFrame: baseline - day 28
measure: Days of hospitalization and in ICU
timeFrame: baseline - day 28
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Univ.-klinik f. Herz-, Thorax-, Gefäßchirurgische Anästhesiologie und lntensivmedizin, Medizinische Universität Graz
state: Steiermark
city: Innsbruck
country: Austria
facility: Univ. Klinik für Innere Medizin / Gem. Einrichtung für Intensiv- und Notfallmedizin/GE Medizinische Universität Innsbruck
city: Vienna
country: Austria
facility: Department of Anesthesia, General Intensive Care and Pain Control,Medical University of Vienna
city: München
country: Germany
facility: Klinik für Anaesthesiologie, Klinikum der Universität München, Campus Großhadern
state: Bayern
city: Aachen
country: Germany
facility: Klinik für Operative Intensivmedizin und Intermediate Care
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Klinik und Poliklinik für Anästhesiologie und Intensivtherapie / Universitätsklinikum Carl Gustav Carus
state: Sachsen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Operative Intensivmedizin, Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin
city: Göttingen
country: Germany
facility: Georg-August-Universität Göttingen
city: Kiel
country: Germany
facility: Klinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Schleswig-Holstein, Campus Kiel,
city: Mainz
country: Germany
facility: Klinik für Anästhesiologie / Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Mannheim
country: Germany
facility: Klinik für Anästhesiologie und operative Intensivmedizin; Universitätsmedizin Mannheim
city: München
country: Germany
facility: Klinik für Anästhesiologie und Intensivmedizin; Klinikum rechts der Isar der TU München
city: München
country: Germany
facility: Klinik und Poliklinik für Innere Medizin II; Klinikum rechts der Isar der TU München
city: Münster
country: Germany
facility: Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie; Universitätsklinikum Münster
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg, Klinik und Poliklinik für Anästhesiologie
Study officials:
References: