Terminated/Withdrawn

Acute respiratory distress syndrome

Bayer Identifier:

20425

ClinicalTrials.gov Identifier:

NCT04609943

EudraCT Number:

2019-004950-26

EU CT Number:

Not Available

Study to find the highest safe dose of soluble Guanylate Cyclase (sGC) Activator, BAY 1211163 administered as multiple doses by inhalation to patients who cannot breathe by their own and suffer from a type of lung failure that causes fluid to build up in the lungs making breathing difficult (ARDS)

Trial purpose

With this study researchers want to find the highest safe dose of the soluble Guanylate Cyclase (sGC) Activator, BAY 1211163 and how safe and well the study drug works. Furthermore researchers want to gather information on the way the body absorbs, distributes and gets rid of the study drug given as increasing multiple doses by inhalation to patients who cannot breathe by their own and suffer from a type of lung failure that causes fluid to build up in the lungs making breathing difficult (ARDS)

Key Participants Requirements

Sex

All

Age

18 - N/A

Inclusion Criteria
- Intubated, mechanically ventilated moderate or severe ARDS patients [diagnosed according to Berlin definition of ARDS, including PEEP ≥ 5 cmH2O, X-ray, with PaO2/FiO2 between 80 and 200 mmHg (inclusive).
- Initial diagnosis of ARDS prior to study inclusion, confirmation of ongoing moderate or severe ARDS with PaO2/FiO2 between 80 and 200 mmHg (inclusive) during this time under maintained invasive mechanical ventilation.
- Hypoxemia with PaO2/FiO2 between 80 and 200 mmHg (inclusive) maintained for at least 8 hours (recommend to be 12 hours) after screening, despite consent to follow recommendation on ventilator strategy and PEEP management.
- Time from intubation must be ≤ 96h.
- Male and non-pregnant female.
- Informed consent of capable patient or, in case of patient being incapable of giving informed consent, consent for study inclusion will be sought according to applicable laws and regulations.
Exclusion Criteria
- PaO2/FiO2 > 200 mmHg or < 80 mmHg at time of evaluation for inclusion.
- Moribund participants not expected to survive 24 hours (clinical decision).
- Expected duration of invasive mechanical ventilation less than 96 hours (clinical decision).
- History of pneumectomy or lung transplant.
- Current lung malignancy (including lung metastasis), or other malignancy requiring chemotherapy or radiation within the last month.
- History of chronic kidney disease and requiring renal replacement therapy dialysis at screening and/or baseline.
- Chronic liver disease Child-Pugh Class B and C.
- Hypoalbuminemia – serum albumin < 2.0 g/dL.
- Acute left ventricular failure and/or Left Ventricular Ejection Fraction < 30 %.
- Severe bronchopulmonal fistula.
- Clinical suspicion of pulmonary veno-occlusive disease.
- Heart right-sided endocarditis, tumors or mass.
- Rescue procedures already initiated at screening and/or Day 1.
- Use of co-medications involving moderate and strong inhibitors for CYP2C8 liver enzymes one week before assignment to intervention or during intervention.
- Off-label use of medication to treat Coronavirus SARS-CoV-2 virus unless recommended by scientific guidelines and accepted by DMC, investigator and sponsor.
- Plan to participate or past participation (within 30 days prior to Study Day 1) in other interventional studies.

Trial summary

Enrollment Goal

Trial Dates

November 2020 - September 2023

Phase

Phase 1

Could I Receive a placebo

Products

BAY1211163

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed	Klinikum der Stadt Köln gGmbH - Krankenhaus Merheim	Köln, 51109, Germany
Completed	Charité - Universitätsmedizin Berlin	Berlin, 10117, Germany
Completed	Universitätsklinikum Giessen und Marburg	Gießen, 35392, Germany
Completed	Sana-Klinikum Remscheid\|Kardio, Angio, Pneumo u. Intensivmed	Remscheid, 42859, Germany
Withdrawn	Universitätsklinikum Essen	Essen, 45147, Germany
Withdrawn	Universitätsklinikum Schleswig-Holstein (UKSH)	Kiel, 24105, Germany

Primary Outcome

Numbers of participants with treatment emergent adverse events (TEAEs)
Time Frame:
Up to 9 days
Numbers of participants with dose limiting events (DLEs)
A dose limiting event is defined as any of the TEAEs occurring during dosing with BAY1211163 and regarded by the investigators to be related to BAY1211163.
Time Frame:
Day 1 to 7 (may include Day 8)

Secondary Outcome

Values of oxygenation index (OI)
The Oxygenation Index (OI) is calculated by using the fraction of inspired oxygen (FiO2), the partial pressure of oxygen in arterial blood (PaO2) and the mean airway pressure (MPAW)
Time Frame:
Up to 28 days

Trial design

Safety and tolerability of adaptive escalating multiple doses (three times daily) of a soluble Guanylate Cyclase (sGC) Activator Inhale, BAY 1211163, as inhalation in intubated and mechanically ventilated adult patients with moderate and severe Acute Respiratory Distress Syndrome (ARDS). A pilot (phase Ib), first in patient, open label study

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

N/A

Blinding

N/A

Assignment

Single Group Assignment

Trial Arms

Additional Information

Click here to find further information and, after study completion, the study results according to Bayer's transparency standards.