Pulmonary Embolism International THrOmbolysis Study-3

Exclusion Criteria

• •Hemodynamic instability
• •Active bleeding
• •History of non-traumatic intracranial bleeding, any time
• •Acute ischemic stroke or transient ischemic attack (TIA) within the previous 6 months
• •Known central nervous system neoplasm/metastasis
• •Neurologic, ophthalmologic, abdominal, cardiac, thoracic, vascular or orthopedic surgery or trauma within 3 previous weeks
• •Platelet count \< 100 G/L
• •INR \> 1.4. If INR not available: prothrombin time ratio \< 60%. If both INR and prothrombin time ratio are measured, INR is relevant for the assessment of this criterion.
• •Treatment with antiplatelet agents other than (a) acetylsalicylic acid (ASA) ≤ 100 mg once daily or (b) clopidogrel 75 mg once daily or (c) a single loading dose of ASA or clopidogrel. Dual antiplatelet therapy (ASA + clopidogrel) is not allowed.
• •Any direct oral anticoagulant within 12 hours of inclusion
• •Uncontrolled hypertension defined by SBP \> 180 mm Hg at the time of inclusion
• •Known pericarditis or endocarditis
• •Known significant bleeding risk according to the investigator's judgement
• •Administration of thrombolytic agents within the previous 4 days
• •Vena cava filter insertion or pulmonary thrombectomy within the previous 4 days
• •Current participation in another interventional clinical study
• •Previous enrolment in this study
• •Known hypersensitivity to alteplase, gentamicin (a residue of the Actilyse® manufacturing process present in trace amounts), any of the excipients of Actilyse®, or low-molecular weight heparin (LMWH)
• •Known previous immune heparin-induced thrombocytopenia
• •Known severe liver disease (grade ≥ 3) including liver failure, cirrhosis, portal hypertension (esophageal varices) and active hepatitis
• •Acute symptomatic pancreatitis
• •Gastrointestinal ulcers or esophageal varices, documented within the past 3 months
• •Known arterial aneurysm, arterial or venous malformations
• •Pregnancy or parturition within the previous 30 days or current breastfeeding.
• •Women of childbearing potential who do not have a negative pregnancy test at the inclusion visit and do not use one of the following methods of birth control: hormonal contraception or intrauterine device or bilateral tubal occlusion
• •Any other condition that the investigator feels would place the patient at increased risk upon start of the investigational treatment
• •Life expectancy of less than 6 months or inability to complete 6-month follow-up.
• •Patient under legal protection