Acute Respiratory Distress SyndromePhase 2SEALNCT04417036
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)
A Phase 2 study testing BAY1097761 Active Dose 1 and BAY1097761 Active Dose 2 in people with Acute Respiratory Distress Syndrome, run by Bayer at 22 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- BAY1097761 Active Dose 1 and BAY1097761 Active Dose 2
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 22 sitesin 7 countries
- Study dates
- 7 Jul 2020to 28 Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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
Show all 10Show fewer
- 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).
Who cannot join
- 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
Show all 15Show fewer
- 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 locations and contacts
22 sites in 7 countries.
22 sites in 7 countries
France6 sites
Centre Hospitalier Universitaire - Angers
Angers, 49933
Center Hospitalier Michallon - Grenoble
La Tronche, 38700
Hôpital du Nord - Marseille
Marseille, 13915
Hôpital de la Pitié-Salpétrière
Paris, 75013
Cochin - Paris
Paris, 75014
Hôpital Civil - Strasbourg
Strasbourg, 67091
Czechia3 sites
Fakultni nemocnice Kralovske Vinohrady
Prague, 10034
Fakultni nemocnice v Motole
Prague, 150 06
Masaryk Hospital Usti n/L
Ústí nad Labem, 401 13
Germany3 sites
Klinikum der Stadt Köln gGmbH - Krankenhaus Merheim
Cologne, North Rhine-Westphalia, 51109
Universitätsklinikum Schleswig-Holstein (UKSH)
Kiel, Schleswig-Holstein, 24105
Klinikum Oldenburg AöR
Oldenburg, Lower Saxony, 26133
Italy3 sites
Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
Milan, Lombardy, 20089
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, Lombardy, 20122
ASST Santi Paolo e Carlo
Milan, Lombardy, 20142
Spain3 sites
Ciutat Sanitaria i Universitaria de la Vall d'Hebron
Barcelona, 08035
Hospital de la Santa Creu i de Sant Pau
Barcelona, 08041
Corporació Sanitària Parc Taulí
Sabadell, Barcelona, 08208
Austria2 sites
Medizinische Universität Innsbruck
Innsbruck, Tyrol, 6020
Universitätsklinikum AKH Wien
Vienna, 1090
United Kingdom2 sites
University Hospital of Wales
Cardiff, CF14 4XW
Guy's Hospital
London, SE1 9RT
About this study
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
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.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- BAY1097761 Active Dose 1, Placebo to BAY1097761, BAY1097761 Active Dose 2
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAY1097761 Active Dose 1Drug
Participants will receive a lower dose ADM by inhalation
Placebo to BAY1097761Other
Participants will receive Placebo to BAY1097761 by inhalation
BAY1097761 Active Dose 2Drug
Participants will receive a higher dose ADM by inhalation
| Study group | Role | What they receive |
|---|---|---|
| Part A - Active Drug Dose 1 | Experimental | Participants will receive Active Drug Dose 1 for a maximum of 14 days in study phase Part A Receives: Drug: BAY1097761 Active Dose 1 |
| Part A - Active Drug Dose 2 | Experimental | Participants will receive Active Drug Dose 2 for a maximum of 14 days in study phase Part A Receives: Drug: BAY1097761 Active Dose 2 |
| Part A - Placebo | Placebo comparator | Participants will receive Placebo for a maximum of 14 days in study phase Part A Receives: Other: Placebo to BAY1097761 |
| Part B - Active Drug Dose | Experimental | Participants will receive Active Drug 1 or 2 for a maximum of 14 days in study phase Part B Receives: Drug: BAY1097761 Active Dose 1; Drug: BAY1097761 Active Dose 2 |
| Part B - Placebo | Placebo comparator | Participants will receive Placebo for a maximum of 14 days in study phase Part B Receives: Other: Placebo to BAY1097761 |
What is being measured
The primary outcome is the main question the study is designed to answer.
VFS in Part B participants
Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)
Measured: At Day 28
Secondary outcomes (7)
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.
Measured: Up to 7 days
VFS in Part A participants
Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)
Measured: At Day 28
All-cause mortality in Part A and Part B participants
Measured: 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
Measured: At Day 28 and Day 60
Ventilator-free days (VFDs) in Part A and Part B participants
Measured: 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)
Measured: 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)
Measured: At Day 28 and Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start7 Jul 2020
- Primary completion28 Dec 2022
- Study completion28 Dec 2022
Why it stopped: Terminated (based on Part A results, Bayer decided to not continue investigating BAY 1097761 further in Part B; this was not due to any safety data for BAY 1097761)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04417036
- Sponsor's protocol ID
- 19999
- Other IDs
- 2019-001078-27, 2019
- Acronym
- SEAL
- Status last verified
- Mar 2023
- First submitted
- 29 May 2020
- Last updated
- 18 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
Publications
Karagiannidis C, McAuley DF, Thompson BT, Reimer T, Shakery K, Schmitz S, Cortes MN, Ullrich R, Meziani F, Mercat A, Chiumello D, Duska F, Combes A; SEAL Trial Investigators. Safety and efficacy of inhaled PEG-ADM in ARDS patients: a randomised controlled trial. Crit Care. 2025 Oct 23;29(1):448. doi: 10.1186/s13054-025-05617-y.
PubMed 41131549
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04417036
- Acronym / sponsor ID
- SEAL / 19999
- Conditions
- Acute Respiratory Distress Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated (based on Part A results, Bayer decided to not continue investigating BAY 1097761 further in Part B; this was not due to any safety data for BAY 1097761)
- Enrolment
- 90 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 7 Jul 2020 (actual)
- Primary completion
- 28 Dec 2022 (actual)
- Study completion
- 28 Dec 2022 (actual)
- First posted
- 4 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A - Active Drug Dose 1 | Experimental | Drug: BAY1097761 Active Dose 1Participants will receive Active Drug Dose 1 for a maximum of 14 days in study phase Part A |
| Part A - Active Drug Dose 2 | Experimental | Drug: BAY1097761 Active Dose 2Participants will receive Active Drug Dose 2 for a maximum of 14 days in study phase Part A |
| Part A - Placebo | Placebo comparator | Other: Placebo to BAY1097761Participants will receive Placebo for a maximum of 14 days in study phase Part A |
| Part B - Active Drug Dose | Experimental | Drug: BAY1097761 Active Dose 1, Drug: BAY1097761 Active Dose 2Participants will receive Active Drug 1 or 2 for a maximum of 14 days in study phase Part B |
| Part B - Placebo | Placebo comparator | Other: Placebo to BAY1097761Participants will receive Placebo for a maximum of 14 days in study phase Part B |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ≥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
- 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.
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAY1097761 Active Dose 1Participants will receive a lower dose ADM by inhalation | Drug | Part A - Active Drug Dose 1, Part B - Active Drug Dose |
| Placebo to BAY1097761Participants will receive Placebo to BAY1097761 by inhalation | Other | Part A - Placebo, Part B - Placebo |
| BAY1097761 Active Dose 2Participants will receive a higher dose ADM by inhalation | Drug | Part A - Active Drug Dose 2, Part B - Active Drug Dose |
Primary outcome
VFS in Part B participants
Time frame: At Day 28
Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)
7 secondary outcomes
CUI in Part A participants
Time frame: Up to 7 days
VFS in Part A participants
Time frame: At Day 28
All-cause mortality in Part A and Part B participants
Time 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
Time frame: At Day 28 and Day 60
Ventilator-free days (VFDs) in Part A and Part B participants
Time frame: Within Day 28 and Day 60
VFS in Part A and Part B participants
Time frame: At Day 60
Integrated analysis on VFS invoving all participants from Part A and Part B
Time frame: At Day 28 and Day 60
Results and safety
The study was stopped early (reason given: Terminated (based on Part A results, Bayer decided to not continue investigating BAY 1097761 further in Part B; this was not due to any safety data for BAY 1097761)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2023.
- Derived from this study: PubMed 41131549Karagiannidis C, McAuley DF, Thompson BT, Reimer T, Shakery K, Schmitz S, Cortes MN, Ullrich R, Meziani F, Mercat A, Chiumello D, Duska F, Combes A; SEAL Trial Investigators. Safety and efficacy of inhaled PEG-ADM in ARDS patients: a randomised controlled trial. Crit Care. 2025 Oct 23;29(1):448. doi: 10.1186/s13054-025-05617-y.
- Individual participant dataSharing planned: No. Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
22 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BAY1097761 Active Dose 1 and BAY1097761 Active Dose 2 in people with Acute Respiratory Distress Syndrome, run by Bayer at 22 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in France, Czechia, Germany, Italy, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated (based on Part A results, Bayer decided to not continue investigating BAY 1097761 further in Part B; this was not due to any safety data for BAY 1097761)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VFS in Part B participants (time frame: At Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04417036, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.