Standard-dose Apixaban AFtEr Very Low-dose ThromboLYSis for Acute Intermediate-high Risk Acute Pulmonary Embolism (SAFE-LYSE)
Pulmonary Embolism With Acute Cor Pulmonale, Pulmonary Embolism, Pulmonary Embolism With Pulmonary Infarction
About this trial
This is an interventional treatment trial for Pulmonary Embolism With Acute Cor Pulmonale
Eligibility Criteria
Inclusion Criteria:
- Chest CT angiogram (CTA) evidence of proximal Pulmonary Embolism (PE) with a filling defect in at least one main pulmonary artery or lobar artery
- PE symptom duration ≤14 days
- Intermediate-high risk PE: defined as RV dysfunction with an RV/LV diameter ≥ 0.9, sPESI > 0, and either troponin > 0.05ng/mL or BNP > 100 pg/mL, and hemodynamically stable (systolic blood pressure > 90mmHg without the use of vasopressor support)
- Randomization within 24 + 4 hours of anticoagulation
- Signed and dated informed consent obtained from subject or legally authorized representative before initiation of any study procedures
Exclusion Criteria:
- Weight > 130kg or < 40 kg on day of randomization
- Stroke or transient ischemic attack (TIA), head trauma, or other active intracranial or intraspinal disease within one year
- Recent (within one month) or active bleeding from a major organ
- Major surgery within 14 days
- Clinician deems the subject too high-risk for bleeding using HAS-BLED criteria
- History of any hematologic disease or coagulopathy
- Cirrhosis (as determined by Child-Pugh B or C)
- History of heparin-induced thrombocytopenia (HIT)
- Hemodynamic instability defined as systolic blood pressure (SBP) less than 90mmHg and/or use of vasopressors for greater than 15 minutes
- Severe hypertension as defined as SBP greater than 180mmHg
- Cardiac arrest or active cardiopulmonary resuscitation (CPR)
- Receiving neuraxial anesthesia or undergoing spinal puncture
- Patient with prosthetic heart valves
- Evidence of irreversible neurological compromise
- Evidence of poor functional status
- History of major gastrointestinal bleed within the last month
- Active gastric or duodenal ulcers
- Use of thrombolytics or glycoprotein IIb/IIIa antagonists within 3 days prior to diagnosis
- Lovenox administration within 12 hours of randomization
- Direct-acting oral anticoagulant use (dabigatran, rivaroxaban, apixaban, or edoxaban) with last known dose within 48 hours
- Hemoglobin < 10 g/dL
- Creatinine clearances < 60 mL/min
- Platelets < 100 thousand/µL
- INR > 1.4
- Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2 times upper limit of normal (ULN)
- Total bilirubin (TBL) ≥ 1.5 times ULN (except due to confirmed Gilbert's syndrome)
- Patient is pregnant (positive pregnancy test; women of childbearing capacity must be tested prior to enrollment) or breast feeding
- Patient who is a prisoner, or if subject who becomes compulsory detained
- Active cancer defined as diagnosis of cancer within six months before the study inclusion, or receiving treatment for cancer at the time of inclusion or any treatment for cancer during 6 months prior to randomization, or recurrent locally advanced or metastatic cancer
- Known allergy, hypersensitivity or thrombocytopenia from heparin, tPA, or apixaban or iodinated contrast except for mild-moderate contrast allergies for which steroid pre-medication can be administered within 12 hours prior to the CTA
- HIV/AIDS
Sites / Locations
- Cedars-Sinai Medical Center
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Alteplase & Unfractionated Heparin & Apixaban
Placebo & Unfractionated Heparin & Apixaban
Alteplase 24mg intravenous infusion for 20 minutes followed by unfractionated heparin intravenous infusion over 24 hours followed by apixaban 10mg tablet twice-daily for one week followed by apixaban 5mg tablet twice-daily for at least 6 months.
Alteplase placebo solution 24mg intravenous infusion for 20 minutes followed by unfractionated heparin intravenous infusion over 24 hours followed by apixaban 10mg tablet twice-daily for one week followed by apixaban 5mg tablet twice-daily for at least 6 months.