The TRISTARDS trial - ThRombolysIS Therapy for ARDS A study to testwhether different doses of alteplase help people with severe breathingproblems because of COVID 19.

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 270

Inclusion Criteria

1.Age >= 18 years (or above legal age, e.g. UK >=16 years)
2.ARDS with PaO2 (see note 1)/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)
Note 1: or estimation of PaO2/FiO2 from pulse oximetry (SpO2/FiO2)
3.SARS-CoV-2 positive (laboratory-confirmed RT-PCR test)
4.Fibrinogen level >= upper limit of normal
5.D-Dimer >= 3-fold of 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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 178

Exclusion Criteria

1. Massive confirmed pulmonary embolism (PE) with haemodynamic instability at trial entry
2. Patients on mechanical ventilation for longer than 48 hours
3. 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
4. Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order
5. In the opinion of the investigator, is not expected to survive for > 48 hours after admission
6. Patients with known hypersensitivity to the active substance
alteplase, gentamicin (a trace residue from the manufacturing process)
or to any of the excipients
7. Significant bleeding disorder at present or within the past 3 months,
known haemorrhagic diathesis
8. 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
9. Any history of central nervous system damage (i.e. neoplasm,
aneurysm, intracranial or spinal surgery)
10. History or evidence or suspicion of intracranial haemorrhage
including sub-arachnoid haemorrhage
11. Severe uncontrolled arterial hypertension (according to the
investigator`s judgement)
12. Major surgery or significant trauma in the past 10 days, recent
trauma to head or cranium
13. Cardiac arrest and/or cardiopulmonary resuscitation during the
current hospital stay
14. Obstetrical delivery within the past 10 days
15. Severe hepatic dysfunction, including biopsy confirmed hepatic
cirrhosis, portal hypertension, hepatic encephalopathy, or active
hepatitis
16. Bacterial endocarditis, pericarditis
17. Acute pancreatitis
18. Documented ulcerative gastro-intestinal disease during the last 3
months
19. Severe heart failure (New York Heart Association Class IV)
20. Arterial aneurysms, arterial/venous malformations
21. Malignancy (Stage IV)
22. Haemorrhagic stroke or stroke of unknown origin at any time
23. Ischaemic stroke or transient ischaemic attack (TIA) in the
preceding 6 months
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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