Reduced-dose versus full-dose systemic thrombolysis for high-risk pulmonary embolism: a multicentre, randomised, open-label, blinded-endpoint trial

Pulmonary embolism

The primary efficacy endpoint (non-inferiority) is the incidence of all-cause mortality within 7 days, CPR and/or VA-ECMO within 7 days, recurrent PE within 7 days, clinical deterioriation within 24 hours, lack of clinical improvement at 6 hours, in the per protocol (PP) population.

All-cause mortality at 7 days and 30 days analysed as time to all-cause mortality, PE-related mortality at 7 days and 30 days analysed as time to PE-related death, CPR and/or VA-ECMO within 7 days, Clinical deterioration within 24 hours defined as life-threatening haemodynamic or respiratory decline during IMP administration requiring CPR, endotracheal intubation or VA-ECMO, or after IMP administration by the same criteria or by an increase in SCAI SHOCK stage, Lack of clinical improvement within 6 hours defined as unchanged SCAI SHOCK stage or unchanged or rising Fraction of Inspired Oxygen (FiO2) required to maintain oxygen saturation ≥94%, Time to clinical stabilisation defined as time from randomisation to the timepoint at which stabilisation critera have been continuously fulfilled for at least 30 minute. This is defined as 30 minutes after discontinuation of vasoactive drugs, provided that SBP ≥90 mmHg or MAP ≥65 mmHg is maintained without vasoactive drugs or mechanical circulatory support (MCS) throughout this period., For patients included due to respiratory failure, stabilisation is defined as 30 minutes after achieving oxygen saturation ≥94% (or the treating physician’s predefined target oxygen saturation in patients with underlying chronic lung disease) maintained with facemask oxygen ≤8 L O₂/min or high-flow nasal oxygen or non-invasive ventilation with FiO₂ ≤50% without intubation throughout this period., Recurrent PE at 7 days and 30 days, Win ratio for efficacy includes (in this order): all-cause mortality within 7 days, CPR and/or VA-ECMO within 7 days, clinical deterioration within 24 hours (described in 8.2.2), lack of clinical improvement at 6 hours (described in 8.2.2) recurrent PE within 7 days, time to clinical stabilisation, Rescue treatment, defined as need for additional alteplase, catheter-directed intervention, surgical embolectomy, or VA-ECMO before stabilisation, LOS in ICU / HDU and hospital within 30 days, Major bleeding at 48 hours, 7 days and 30 days analysed as time to major bleeding according to ISTH, Bleeding requiring urgent medical intervention at 48 hours, 7 days and 30 days analysed as time to bleeding requiring urgent medical intervention, Intracerebral bleeding, detected on brain imaging (computed tomography, CT or magnetic resonance imaging, MRI) performed in case of neurological signs, at 48 hours and 7 days analysed as time to intracerebral bleeding, Net clinical benefit including severe clinically significant bleeding major bleeding within 7 days, all-cause mortality within 7 days, CPR and/or VA-ECMO within 7 days, recurrent PE within 7 days,clinical deterioration within 24 hours, lack of clinical improvement at 6 hours, Invasive or non invasive mechanical ventilation initiation within 7 days, Key secondary endpoint: The key secondary endpoint (superiority) is the incidence within 7 days of severe clinically significant bleeding, defined as major bleeding according to International Society on Thrombosis and Haemostasis (ISTH) (20) or bleeding requiring urgent medical intervention, in the modified intention-to-treat (mITT) population.

No related papers found yet.