The TRISTARDS trial - ThRombolysIS Therapy for ARDS A study to test whether different doses of alteplase help people with severe breathing problems because of COVID 19.

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 320

Inclusion Criteria

1.Age = 18 years (or above legal age)
2.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)
3.SARS-CoV-2 positive (laboratory-confirmed RT-PCR test)
4.Fibrinogen level = 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 Good Clinical Practice (GCP) and local legislation prior to admission to the trial.

Are the trial subjects under 18? yes
Number of subjects for this age range: 8
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

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. Mechanical ventilation for longer than 48 hours
4. Chronic pulmonary disease i.e. with known 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
5. Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order
6. In the opinion of the investigator not expected to survive for > 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. 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 6 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

Further criteria apply.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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