The TRISTARDS trial - ThRombolysIS Therapy for ARDS A Phase IIb/III operationally seamless, open-label, randomised, sequential, parallel-group adaptive study to evaluate the efficacy and safety of daily intravenous alteplase treatment given up to 5 days on top of standard of care (SOC) compared with SOC alone, in patients with acute respiratory distress syndrome (ARDS) triggered by COVID-19.
- Conditions
- Acute lung injury10037454shocklung10047438
- Registration Number
- NL-OMON52082
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
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
- with respiratory failure
*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 GCP and
local legislation prior to admission to the trial.
See protocol section 3.3.2.
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) <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, is 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. 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Time to clinical improvement or hospital discharge up to Day 28, defined as the<br /><br>time from randomisation to either an improvement of two points on the 11-point<br /><br>WHO Clinical Progression Scale or discharge from the hospital, whichever comes<br /><br>first. </p><br>
- Secondary Outcome Measures
Name Time Method <p>- All cause mortality at Day 28<br /><br>- Number of ventilator-free days from start of treatment to Day 28<br /><br>- Improvement of Sequential (sepsis-related) Organ Failure Assessment (SOFA)<br /><br>score by >=2 points from baseline to end of Day 6<br /><br>- Major bleeding events (MBE) (according to International Society on Thrombosis<br /><br>and Haemostasis [ISTH] definition until Day 6<br /><br>- Daily average PaO2/FiO2 ratio (or inferred PaO2/FiO2 ratio from SpO2) change<br /><br>from baseline to Day 6<br /><br>- All-cause mortality or on mechanical ventilation at Day 28<br /><br>- Treatment failure defined as all cause mortality or mechanical ventilation at<br /><br>Day 28<br /><br>- Number of oxygen-free days up to Day 28<br /><br>- Length of hospital stay up to Day 28<br /><br>- PaO2/FiO2 ratio (or inferred PaO2/FiO2 ratio from SpO2) change from baseline<br /><br>to Day 6</p><br>