Acute lung injury shocklung
Conditions
Interventions
Treatment with Alteplase IV.
Part 1 of the trial (1:1:1 ratio):
Dosing regimen A (based on your body weight):
• Initial dose of alteplase will be (0,3 mg/kg body weight) given intravenously
over a
Sponsors
Boehringer Ingelheim
Eligibility
Age
12 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years (or above legal age) 2. ARDS with PaO2*/FiO2 ratio >100 and = lower limit of normal 5. D-Dimer >= upper limit of normal (ULN) according to local laboratory 6. Signed and dated written informed consent in accordance with ICH GCP and local legislation prior to admission to the trial. See protocol section 3.3.2.
Exclusion criteria
Exclusion criteria: 1. 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. 2. Indication for therapeutic dosages of anticoagulants at trial entry. 3. Patients on mechanical ventilation for longer than 48 hours 4. Chronic pulmonary disease i.e. with known forced expiratory volume in 1 second (FEV1) 48 hours after screening. 7. Planned interventions during the first 5 days after randomization, such as surgery, insertion of central catheter or arterial line, drains, etc. 8. Patients with known hypersensitivity to the active substance alteplase, gentamicin (a trace residue from the manufacturing process) or to any of the excipients 9. Significant bleeding disorder at present or within the past 3 months, known haemorrhagic diathesis 10. Patients receiving effective oral anticoagulant treatment, e.g. vitamin K antagonists with INR >1.3, or any direct oral anticoagulant within the past 48 hours 11. Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery) 12. History or evidence or suspicion of intracranial haemorrhage including sub-arachnoid haemorrhage 13. Severe uncontrolled arterial hypertension (according to the investigator`s judgement) 14. Major surgery or significant trauma in the past 10 days, recent trauma to head or cranium 15. Cardiac arrest and/or cardiopulmonary resuscitation during the current hospital stay 16. Obstetrical delivery within the past 10 days 17. Severe hepatic dysfunction i.e. Child-Pugh B and C, including biopsy confirmed hepatic cirrhosis, portal hypertension, hepatic encephalopathy, or active hepatitis 18. Bacterial endocarditis, pericarditis 19. Acute pancreatitis 20. Documented ulcerative gastro-intestinal disease during the last 3 months 21. Severe heart failure (New York Heart Association Class IV) 22. Arterial aneurysms, arterial/venous malformations 23. Malignancy (Stage IV) with increased bleeding risk 24. Haemorrhagic stroke or stroke of unknown origin at any time 25. Ischaemic stroke or transient ischaemic attack (TIA) in the preceding 6 months Further criteria apply, see protocol section 3.3.3.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to clinical improvement or hospital discharge up to Day 28, defined as the time from randomisation to either an improvement of two points on the 11-point WHO Clinical Progression Scale or discharge from the hospital, whichever comes first. | — |
Secondary
| Measure | Time frame |
|---|---|
| - All cause mortality at Day 28 - Number of ventilator-free days from start of treatment to Day 28 - Improvement of Sequential (sepsis-related) Organ Failure Assessment (SOFA) score by >=2 points from baseline to end of Day 6 - Major bleeding events (MBE) (according to International Society on Thrombosis and Haemostasis [ISTH] definition until Day 6 - Daily average PaO2/FiO2 ratio (or inferred PaO2/FiO2 ratio from SpO2) change from baseline to Day 6 - All-cause mortality or on mechanical ventilation at Day 28 - Treatment failure defined as all cause mortality or mechanical ventilation at Day 28 - Number of oxygen-free days up to Day 28 - Length of hospital stay up to Day 28 - PaO2/FiO2 ratio (or inferred PaO2/FiO2 ratio from SpO2) change from baseline to Day 6 | — |
Countries
Netherlands
Outcome results
None listed