stop_circleTerminated/Withdrawn

Acute respiratory distress syndrome

This study collects information on the safety of inhaled pegylated adrenomedullin (PEG-ADM), how the drug is tolerated and how it affects patients suffering from a type of lung failure that cause fluid to build up in the lungs making breathing difficult (ARDS)

Trial purpose

The study is composed of two parts. In part A of the study two active doses of inhaled pegylated adrenomedullin (PEG-ADM) will be compared regarding safety and efficacy to a substance that has no therapeutic effect (placebo) in order to find an optimal and safe of the study drug. In part B of the study the highest dose that is considered safe and has demonstrated efficacy will be taken forward to collect information how well patients suffering from Acute Respiratory Distress Syndrome (ARDS) respond to treatment with inhaled pegylated adrenomedullin (PEG-ADM) compared to treatment with placebo. ARDS is a type of lung failure that cause fluid to build up in the lungs making breathing difficult or impossible.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - ≥18 years of age at the time of inclusion into study.

    - Invasively mechanically ventilated acute respiratory distress syndrome [ARDS] patients (diagnosed according to Berlin definition of ARDS, including positive end-expiratory pressure [PEEP] of ≥5 cm H2O, X-ray (or CT scan) indicative of ARDS: bilateral opacities not fully explained by cardiac failure, fluid overload, lobar/lung collapse, effusions or nodules).

    - Initial diagnosis of mild, moderate or severe ARDS prior to study inclusion, with acute onset of ARDS within 1 week after suspected trigger factor of

     -- Pneumonia

     -- Aspiration

     -- Sepsis

     -- Pancreatitis

    - Prior to randomization, hypoxemia with PaO2:FiO2 ≤300 mmHg continuously observed for a period of ≥4 hours (with values of ≥2 arterial blood gas [ABG] analyses during that time, with the last value obtained timely (generally ≤3 hours) prior to randomization), under ventilation with minimum PEEP ≥8 cm H2O.

    - Time from first meeting the last diagnostic ARDS criterion (Berlin criteria) to randomization must be ≤48 hours.

    - For Study Part A: ARDS patients for whom measurements of extra-vascular lung water are regarded as medically indicated by the treating physician, and these measurements are planned as part of their clinical care, from Study Day 1 up to Study Day 7 (if then still intubated).
  • - Any value of a PaO2:FiO2 ratio >300 mmHg within a time interval of 4 hours before randomization

    - Rescue therapy (e.g. inhalation of nitric oxide gas and/or inhalation of prostacyclin analogues, or extra corporeal membrane oxygenation [ECMO] / extra corporeal CO2 removal [ECCO2R]) already initiated at screening and/or Study Day 1 (prior to first dose of the study intervention)

    - Moribund participants not expected to survive 24 hours (clinical decision)

    - Expected duration of invasive mechanical ventilation less than 48 hours (clinical decision)

    - History of co-morbidities requiring long-term/home oxygen use (e.g. severe chronic obstructive pulmonary disease [COPD], pulmonary fibrosis) or non-invasive ventilation (except for sleep apnea management), or making weaning per se improbable (e.g. ALS, muscular dystrophy)

    - Smoke inhalation injury, extensive burns or trauma/head injury as concomitant condition

    - History of pneumectomy, lung lobectomy or lung transplant

    - Diffuse alveolar hemorrhage from vasculitis

    - Current lung malignancy (incl. lung metastasis), or other malignancy requiring chemotherapy or radiation within the last month

    - Chronic kidney disease with a history of renal replacement therapy (e.g. dialysis)

    - Chronic liver disease Child-Pugh Class C

    - Chronic heart failure NYHA IV

    - Known hypersensitivity to polyethyleneglycol (PEG, Macrogol)

    - Participation in other interventional studies involving pharmacological interventions, or biological or cell therapy interventions

    - Diagnosis of COVID-19 pneumonia within 6 weeks prior to study inclusion. History of SARS-CoV-2 infection (positive test based on nucleic acid amplification technology or positive antigen test) without COVID-19 pneumonia does not exclude patients

Trial summary

Enrollment Goal
90
Trial Dates
July 2020 - December 2022
Phase
Phase 2
Could I Receive a placebo
Yes
Products
BAY1097761
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Universitätsklinikum AKH WienWien, 1090, Austria
Withdrawn
Medizinische Universität GrazGraz, 8036, Austria
Completed
Fakultni nemocnice Kralovske VinohradyPraha 10, 10034, Czechia
Completed
Masaryk Hospital Usti n/LUsti nad Labem, 401 13, Czechia
Completed
Fakultni nemocnice v MotolePraha 5, 150 06, Czechia
Withdrawn
Kepler Universitätsklinikum Campus IIILinz, 4020, Austria
Completed
Medizinische Universität InnsbruckInnsbruck, 6020, Austria
Completed
Klinikum der Stadt Köln gGmbH - Krankenhaus MerheimKöln, 51109, Germany
Completed
Klinikum Oldenburg AöROldenburg, 26133, Germany
Withdrawn
Medizinische Hochschule Hannover (MHH)Hannover, 30625, Germany
Completed
Hospital de la Santa Creu i de Sant PauBarcelona, 08041, Spain
Completed
Corporació Sanitària Parc TaulíSabadell, 08208, Spain
Completed
Ciutat Sanitaria i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Completed
Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilano, 20122, Italy
Completed
ASST Santi Paolo e CarloMilano, 20142, Italy
Completed
Cochin - ParisPARIS, 75014, France
Completed
Center Hospitalier Michallon - GrenobleLA TRONCHE, 38700, France
Withdrawn
Charité - Universitätsmedizin BerlinBerlin, 10117, Germany
Completed
Centre Hospitalier Universitaire - AngersANGERS CEDEX 09, 49933, France
Completed
Hôpital du Nord - MarseilleMARSEILLE CEDEX 20, 13915, France
Withdrawn
Hospital Universitario de GetafeGetafe, 28905, Spain
Completed
Hôpital de la Pitié-SalpétrièrePARIS, 75013, France
Withdrawn
ASST di MonzaMonza Brianza, 20090, Italy
Withdrawn
Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke PreventionL'Hospitalet de Llobregat, 08907, Spain
Completed
Universitätsklinikum Schleswig-Holstein (UKSH)Kiel, 24105, Germany
Withdrawn
Klinikum der Universität München GrosshadernMünchen, 81377, Germany
Completed
Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.Milano, 20089, Italy
Completed
Hôpital Civil - StrasbourgSTRASBOURG, 67091, France
Withdrawn
Bristol Royal InfirmaryBristol, BS2 8HW, United Kingdom
Completed
University Hospital of WalesCardiff, CF14 4XW, United Kingdom
Withdrawn
Royal Liverpool University HospitalLiverpool, L7 8XP, United Kingdom
Withdrawn
Sci-Res. Institute of Emergency Care n.a. N.V. SklifosovskyMoscow, 129090, Russian Federation
Withdrawn
First City Clinical Hospital n.a. E.E. VolosevichArkhangelsk, 163001, Russian Federation
Withdrawn
Altai Regional Clinical HospitalBarnaul, 656024, Russian Federation
Withdrawn
Regional Clinical Hospital KrasnoyarskKrasnoyarsk, 660022, Russian Federation
Withdrawn
Kemerovo Regional Clinical HospitalKemerovo, 650066, Russian Federation
Withdrawn
Kuban State Medical UniversityKrasnodar, 350072, Russian Federation
Completed
Guy’s HospitalLondon, SE1 9RT, United Kingdom
Withdrawn
Landesklinikum KremsKrems, 3500, Austria
Withdrawn
General Hospital of Athens "Evangelismos"Athens, 10676, Greece
Withdrawn
University General Hospital ATTIKONChaidari, 12462, Greece
Withdrawn
SOTIRIA General Hospital of Chest DiseasesAthens, 11527, Greece
Withdrawn
University General Hospital of HeraklionHeraklion / Crete, 71110, Greece
Withdrawn
General Hospital of LarissaLarissa, 41110, Greece
Withdrawn
Ziekenhuis Gelderse ValleiEde, 6716 RP, Netherlands
Withdrawn
Medisch Spectrum TwenteENSCHEDE, 7512 KZ, Netherlands
Withdrawn
Jeroen Bosch ZiekenhuisDEN BOSCH, 5223 GZ, Netherlands
Withdrawn
Ikazia ZiekenhuisROTTERDAM, 3083 AN, Netherlands
Withdrawn
Canisius Wilhelmina ZiekenhuisNIJMEGEN, 6532 SZ, Netherlands
Withdrawn
Clinique Saint-PierreOTTIGNIES, 1340, Belgium
Withdrawn
Hôpital Erasme/Erasmus ZiekenhuisBRUXELLES - BRUSSEL, 1070, Belgium
Withdrawn
CHU UCL Namur | Intensive CareYvoir, 5530, Belgium
Withdrawn
CU Saint-Luc/UZ St-LucBRUXELLES - BRUSSEL, 1200, Belgium
Withdrawn
Tel-Aviv Sourasky Medical CenterTel Aviv, 6423906, Israel
Withdrawn
Rambam Health CorporationHaifa, 3109601, Israel
Withdrawn
Soroka University Medical CenterBeer Sheva, 8410101, Israel
Withdrawn
Shaare Zedek Medical CenterJerusalem, 9103102, Israel
Withdrawn
Clalit Health Services Rabin Medical Center-Beilinson CampusPetach Tikva, 4941492, Israel
Withdrawn
Vancouver Island Health Authority - Royal Jubilee HospitalVictoria, V8R 1J8, Canada
Withdrawn
Kingston Health Sciences Centre (KGH Site)Kingston, K7L 2V7, Canada
Withdrawn
Toronto General Hospital UHNToronto, M5G 2N2, Canada
Withdrawn
North York General HospitalToronto, M2K 1E1, Canada
Withdrawn
Sunnybrook Health Sciences CentreToronto, M4N 3M5, Canada
Withdrawn
CIUSSS de l’Est-de-l’Ile de Montreal,Installation MaisonneuvMontreal, H1T 2M4, Canada
Withdrawn
Centre intégré universitaire du Nord de l'île de Montréal- HMontréal, H4J 1C5, Canada
Withdrawn
St. Paul's Hospital - VancouverVancouver, V6Z 1Y6, Canada
Withdrawn
Universitätsklinikum EssenEssen, 45147, Germany
Withdrawn
National Taiwan University HospitalTaipei, 100, Taiwan
Withdrawn
Kaohsiung Medical University Chung-Ho Memorial HospitalKaohsiung, 807, Taiwan
Withdrawn
Derriford HospitalPlymouth, PL6 8DH, United Kingdom
Withdrawn
Taichung Veterans General HospitalTaichung, 40705, Taiwan
Withdrawn
Taipei Veterans General HospitalTaipei, 11217, Taiwan
Withdrawn
St Vincents University HospitalDublin, DUBLIN 4, Ireland
Withdrawn
Asan Medical CenterSeoul, 05505, Korea, Republic Of
Withdrawn
Seoul National University Bundang HospitalSeongnam-si, 13620, Korea, Republic Of
Withdrawn
Severance Hospital, Yonsei University Health SystemSeoul, 03722, Korea, Republic Of
Withdrawn
Ajou University HospitalSuwon, 443-721, Korea, Republic Of
Withdrawn
Pulmonary & Critical Care Seoul National University BoramaeSeoul, 07061, Korea, Republic Of
Withdrawn
St James' HospitalDublin, D08 NHY1, Ireland
Withdrawn
Aalborg Universitetshospital, Anesthesiology dept.Aalborg, 9000, Denmark
Withdrawn
Sjællands Universitetshospital Køge - Anesthesiological DeptKøge, 4600, Denmark
Withdrawn
Hôpital Cantonal Universitaire de GenèveGenève, 1205, Switzerland
Withdrawn
UniversitätsSpital ZürichZürich, 8091, Switzerland
Withdrawn
Beaumont HospitalDublin, 9, Ireland
Withdrawn
University College Hospital GalwayGalway, Ireland
Withdrawn
Taunton and Somerset HospitalTaunton, TA1 5DA, United Kingdom
Withdrawn
Royal Victoria HospitalBelfast, BT12 6BA, United Kingdom
Withdrawn
Wythenshawe HospitalManchester, M23 9LT, United Kingdom
Withdrawn
Spitalul Clinic Judetean de Urgenta „Pius Brinzeu” TimisoaraTimisoara, Romania
Withdrawn
Sp. Univ. de Urgenta Militar Central Dr. Carol DavilaBucuresti, 010825, Romania
Withdrawn
Institutul Clinic FundeniBucuresti, 22328, Romania
Withdrawn
Spitalul Universitar de Urgenta EliasBucharest, 11461, Romania
Withdrawn
Eszak-Pesti Centrumkorhaz-HonvedkorhazBudapest, 1134, Hungary
Withdrawn
Debreceni Egyetem Klinikai KozpontDebrecen, 4032, Hungary
Withdrawn
Fakultna Nemocnica s poliklinikou F.D.RooseveltaBanska Bystrica, 975 17, Slovakia
Withdrawn
Centro Hospitalar Vila Nova de Gaia/Espinho | Unit 1 - Clinical Research OfficePorto, 4434-502, Portugal
Withdrawn
Hospital da Luz - LisboaLisboa, 1500-650, Portugal
Withdrawn
Nemocnica AGEL Zvolen, a.s.Zvolen, 960 01, Slovakia
Withdrawn
HUS, Meilahden sairaalaHelsinki, 00290, Finland
Withdrawn
Tampereen yliopistollinen sairaala, keskussairaalaTampere, 33520, Finland
Withdrawn
Kuopion yliopistollinen sairaalaKuopio, 70210, Finland
Withdrawn
Bata HospitalZlin, 762 75, Czechia
Withdrawn
Fakultni nemocnice u sv. AnnyBrno, 656 91, Czechia
Withdrawn
Ospedale regionale di LuganoLugano, 6900, Switzerland

Primary Outcome

  • VFS in Part B participants
    Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)
    date_rangeTime Frame:
    At Day 28

Secondary Outcome

  • CUI in Part A participants
    Clinical Utility Index (CUI) is a summary measure used to compare different treatments, the index score will range between 0 and 1.
    date_rangeTime Frame:
    Up to 7 days
  • VFS in Part A participants
    Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)
    date_rangeTime Frame:
    At Day 28
  • All-cause mortality in Part A and Part B participants
    date_rangeTime Frame:
    At Day 28, Day 60 and Day 90
  • Proportion of participants who still require invasive mechanical ventilation support in Part A and Part B participants
    date_rangeTime Frame:
    At Day 28 and Day 60
  • Ventilator-free days (VFDs) in Part A and Part B participants
    date_rangeTime Frame:
    Within Day 28 and Day 60
  • VFS in Part A and Part B participants
    Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)
    date_rangeTime Frame:
    At Day 60
  • Integrated analysis on VFS invoving all participants from Part A and Part B
    Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)
    date_rangeTime Frame:
    At Day 28 and Day 60

Trial design

Safety and efficacy of inhaled pegylated adrenomedullin (PEG-ADM) in patients suffering from Acute Respiratory Distress Syndrome (ARDS): a double-blind, randomized, placebo-controlled, multicenter Phase 2a/b clinical trial
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
5