This is a study in adults with severe breathing problems because of COVID-19. People who are in hospital on breathing support can participate in the study. The purpose of the study is to find out whether a medicine called alteplase helps people get better faster. The study has 2 parts. In the first part, participants are put into 3 groups by chance. Participants in 2 of the groups get 2 different doses of alteplase, in addition to standard treatment. Participants in the third group get standard treatment. In the second part of the study, participants are put into 2 groups by chance. One group gets alteplase and standard treatment. The other group gets only standard treatment. Alteplase is given as an infusion into a vein. In both study parts, treatments are given for 5 days. Doctors monitor patients and check whether their breathing problems improve. They compare results between the groups after 1 month. Participants are in the study for 3 months.
Drug: Alteplase
Alteplase
Procedure: Standard of care
Standard of Care (SOC) includes any supportive measures applied in hospital, specifically on an intensive care unit (ICU), such as for example the use of non-invasive or invasive ventilation, oxygen masks, haemodynamic support, if needed, sedation, as well as medical therapies commonly used in patients suffering from acute respiratory distress syndrome (ARDS) or its complications. SOC should include best possible treatment regimen established locally and should be in line with current guidelines for ARDS treatment.
Inclusion Criteria:
- Age ≥ 18 years (or above legal age, e.g. UK ≥16 years)
- ARDS with PaO2*/FiO2 ratio >100 and ≤300, either on non-invasive ventilator support,
OR on mechanical ventilation (<48 hours since intubation),
- with bilateral opacities in chest X-ray or CT scan (not fully explained by
effusions, lobar/lung collapse, or nodules)
- with respiratory failure (not fully explained by cardiac failure/fluid overload)
(*or estimation of PaO2/FiO2 from pulse oximetry (SpO2/FiO2))
- SARS-CoV-2 positive (laboratory-confirmed reverse transcription polymerase chain
reaction (RT PCR) test)
- Fibrinogen level ≥ lower limit of normal (according to local laboratory)
- D-Dimer ≥ upper limit of normal (ULN) according to local laboratory
- Signed and dated written informed consent in accordance with ICH Good Clinical
Practice (GCP) and local legislation prior to admission to the Trial
Exclusion Criteria:
- Massive confirmed pulmonary embolism (PE) with haemodynamic instability at trial
entry, or any (suspected or confirmed) PE that is expected to require therapeutic
dosages of anticoagulants during the treatment period
- Indication for therapeutic dosages of anticoagulants at trial entry
- Patients on mechanical ventilation for longer than 48 hours
- Chronic pulmonary disease i.e. with known forced expiratory volume in 1 second (FEV1)
<50%, requiring home oxygen, or oral steroid therapy or hospitalisation for
exacerbation within 12 months, or significant chronic pulmonary disease in the
Investigator's opinion, or primary pulmonary arterial hypertension
- Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order
- In the opinion of the investigator not expected to survive for > 48 hours after
admission
- Planned interventions during the first 5 days after randomisation, such as surgery,
insertion of central catheter or arterial line, drains, etc.
- Patients with known hypersensitivity to the active substance alteplase, gentamicin (a
trace residue from the manufacturing process) or to any of the excipients
- Significant bleeding disorder at present or within the past 3 months, known
haemorrhagic diathesis
- Patients receiving effective oral anticoagulant treatment, e.g. vitamin K antagonists
with International normalised ratio (INR) >1.3, or any direct oral anticoagulant
within the past 48 hours Further exclusion criteria apply.
LKH Klagenfurt am Woerthersee
Klagenfurt, Austria
Wiener Gesundheitsverbund Klinik Favoriten
Vienna, Austria
ULB Hopital Erasme
Bruxelles, Belgium
Centre Hospitalier Universitaire de Liège
Liège, Belgium
Ottignies - HOSP St-Pierre
Ottignies, Belgium
Hospital Mae de Deus
Porto Alegre, Brazil
HOP Bicêtre
Le Kremlin Bicêtre cedex, France
HOP Roger Salengro
Lille, France
HOP Melun-Sénart
Melun, France
HOP Hôtel-Dieu
Nantes, France
HOP Européen G. Pompidou
Paris cedex 15, France
HOP Cochin
Paris, France
HOP Robert Debré
Reims, France
HOP Civil
Strasbourg cedex, France
Medizinische Hochschule Hannover
Hannover, Germany
Universitätsklinikum Heidelberg
Heidelberg, Germany
Universitätsklinikum Leipzig
Leipzig, Germany
Universitätsklinikum Mannheim GmbH
Mannheim, Germany
Klinikum der Universität München - Campus Großhadern
München, Germany
Petrus-Krankenhaus
Wuppertal, Germany
King George Hospital
Visakhapatnam, India
IRCCS San Raffaele
Milano, Italy
Istituto Clinico Humanitas
Rozzano (MI), Italy
Hospital Miri
Miri, Malaysia
Hospital Cardiologica Aguascalientes
Aguascalientes, Mexico
Gelre Ziekenhuizen Apeldoorn
Apeldoorn, Netherlands
Rijnstate Hospital
Arnhem, Netherlands
Canisius-Wilhelmina ziekenhuis
Nijmegen, Netherlands
City Clinical Hospital # 40 of the Moscow Health Department
Moscow, Russian Federation
Moscow 1st State Med.Univ.n.a.I.M.Sechenov
Moscow, Russian Federation
City Clinical Emergency Hospital
Ryazan, Russian Federation
State Budget Institution of Healthcare Leningradskaya region "Kirovskaya Interdistrict Hospital"
Saint Petersburg, Russian Federation
Hospital del Mar
Barcelona, Spain
Hospital Vall d'Hebron
Barcelona, Spain
Hospital Puerta del Mar
Cádiz, Spain
CS Parc Taulí
Sabadell, Spain
Izmir Dr. Suat Seren Gogus Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi
Izmir, Turkey