Clinical trial NCT04417036: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Respiratory Distress Syndrome
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-06-04
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* ≥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).

Exclusion Criteria:

* 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

Primary outcomes:
measure: VFS in Part B participants
timeFrame: At Day 28
Secondary outcomes:
measure: CUI in Part A participants
timeFrame: Up to 7 days
measure: VFS in Part A participants
timeFrame: At Day 28
measure: All-cause mortality in Part A and Part B participants
timeFrame: At Day 28, Day 60 and Day 90
measure: Proportion of participants who still require invasive mechanical ventilation support in Part A and Part B participants
timeFrame: At Day 28 and Day 60
measure: Ventilator-free days (VFDs) in Part A and Part B participants
timeFrame: Within Day 28 and Day 60
measure: VFS in Part A and Part B participants
timeFrame: At Day 60
measure: Integrated analysis on VFS invoving all participants from Part A and Part B
timeFrame: At Day 28 and Day 60
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
state: Tirol
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Usti nad Labem
country: Czechia
facility: Masaryk Hospital Usti n/L
city: Angers Cedex 09
country: France
facility: Centre Hospitalier Universitaire - Angers
city: La Tronche
country: France
facility: Center Hospitalier Michallon - Grenoble
city: Marseille Cedex 20
country: France
facility: Hôpital du Nord - Marseille
city: Paris
country: France
facility: Hôpital de la Pitié-Salpétrière
city: Paris
country: France
facility: Cochin - Paris
city: Strasbourg
country: France
facility: Hôpital Civil - Strasbourg
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg AöR
state: Niedersachsen
city: Köln
country: Germany
facility: Klinikum der Stadt Köln gGmbH - Krankenhaus Merheim
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein (UKSH)
state: Schleswig-Holstein
city: Milano
country: Italy
facility: Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Milano
country: Italy
facility: ASST Santi Paolo e Carlo
state: Lombardia
city: Sabadell
country: Spain
facility: Corporació Sanitària Parc Taulí
state: Barcelona
city: Barcelona
country: Spain
facility: Ciutat Sanitaria i Universitaria de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: Guy's Hospital
Study officials:
References: