a study to test whether different doses of alteplase help people with severe breathing problems because of covid-19

Conditions: Acute Respiratory Distress Syndrome

Summary: 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.


Eligibility criteria:
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.