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)

Acute Respiratory Distress Syndrome Clinical Trial

— SEAL  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04417036
• Other study ID #: 19999
• Secondary ID: 2019-001078-27
• Status: Terminated
• Phase: Phase 2
• Start date: July 7, 2020
• Est. completion date: December 28, 2022

Study information

• Verified date: March 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 90
• Est. completion date: December 28, 2022
• Est. primary completion date: December 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• BAY1097761 Active Dose 1
Participants will receive a lower dose ADM by inhalation

Other:
• Placebo to BAY1097761
Participants will receive Placebo to BAY1097761 by inhalation

Drug:
• BAY1097761 Active Dose 2
Participants will receive a higher dose ADM by inhalation

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck	Tirol
Austria	Universitätsklinikum AKH Wien	Wien
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Fakultni nemocnice v Motole	Praha 5
Czechia	Masaryk Hospital Usti n/L	Usti nad Labem
France	Centre Hospitalier Universitaire - Angers	Angers Cedex 09
France	Center Hospitalier Michallon - Grenoble	La Tronche
France	Hôpital du Nord - Marseille	Marseille Cedex 20
France	Cochin - Paris	Paris
France	Hôpital de la Pitié-Salpétrière	Paris
France	Hôpital Civil - Strasbourg	Strasbourg
Germany	Universitätsklinikum Schleswig-Holstein (UKSH)	Kiel	Schleswig-Holstein
Germany	Klinikum der Stadt Köln gGmbH - Krankenhaus Merheim	Köln	Nordrhein-Westfalen
Germany	Klinikum Oldenburg AöR	Oldenburg	Niedersachsen
Italy	ASST Santi Paolo e Carlo	Milano	Lombardia
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano	Lombardia
Italy	Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.	Milano	Lombardia
Spain	Ciutat Sanitaria i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital de la Santa Creu i de Sant Pau	Barcelona
Spain	Corporació Sanitària Parc Taulí	Sabadell	Barcelona
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Guy's Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Austria,  Czechia,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	VFS in Part B participants	Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)	At Day 28
Secondary	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.	Up to 7 days
Secondary	VFS in Part A participants	Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)	At Day 28
Secondary	All-cause mortality in Part A and Part B participants		At Day 28, Day 60 and Day 90
Secondary	Proportion of participants who still require invasive mechanical ventilation support in Part A and Part B participants		At Day 28 and Day 60
Secondary	Ventilator-free days (VFDs) in Part A and Part B participants		Within Day 28 and Day 60
Secondary	VFS in Part A and Part B participants	Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)	At Day 60
Secondary	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)	At Day 28 and Day 60

External Links

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