The OVERALL OBJECTIVE of this investigation is to determine whether very low-dose intravenous tissue-type plasminogen activator \[tPA\] (24 mg) + standard anticoagulation therapy (intravenous heparin) for treatment of acute PE (pulmonary embolism) in intermediate-high risk patients will have superior clot lysis (breakdown of clot) by chest CTA (computed tomography angiography) at 24 ± 6 hours post infusion compared to standard of care treatment alone. Acute intermediate-high risk PE patients are those with acute symptoms \<14 days), simplified Pulmonary Embolism Severity Index (sPESI)\>0, normal systemic arterial blood pressure (\>90mmHg) without vasopressor support, elevated biomarkers (troponin or BNP), and evidence of RV dysfunction (right ventricular to left ventricular ratio\>0.9).The study is planned to evaluate the reduction in clot burden based on the obstruction index using the Refined Modified Miller Score (RMMS), improvement in right ventricular (RV) function, and overall safety in the two treatment groups. 40 Subjects with intermediate-high risk PE (hemodynamically stable PE with a RV/LV ratio ≥ 0.9, elevated biomarkers, and sPESI\>0) will be recruited and randomized to one of two treatment groups: 24mg of systemic (IV) tPA + IV unfractionated heparin versus saline placebo + IV unfractionated heparin. After delivery of the systemic (IV) tPA/placebo, patients will continue IV unfractionated heparin therapy for at least 24 hours. If there is no evidence of active bleeding nor significant hemoglobin drop (i.e., ≥ 2 mg/dL), patients will be transitioned to standard dose apixaban, 10 mg twice-daily x one week followed by 5 mg twice-daily for at least 6 months. Some patients will require indefinite apixaban therapy based on patient-specific factors, including unprovoked nature of PE event, and/or persisting DVT/PE risk factors. Finally, consideration will be given for decreasing the apixaban dose to 2.5 mg twice-daily after 6 months. Apixaban was selected as the anticoagulant of choice due to its very favorable bleeding profile in large clinical trials, which is an important consideration when prescribing an anticoagulant following systemic thrombolysis. Within 24 ± 6 hours post study drug infusion, a repeat chest CTA and echocardiogram will be performed. sPESI will also be calculated at this timepoint.At Day 30, 180 and 365, all subjects will have clinic visits which will include a physical exam, repeat echocardiogram if previous echo was abnormal, 6 minute walk test (6MWT), quality of life questionnaires, assessment of adverse and bleeding events and a review of concomitant medications including compliance with apixaban. At Days 3, 7, 90 and 270, a remote health check will occur via telephone or email assessing adverse and bleeding events, alongside a review of concomitant medications (including an assessment of compliance with apixaban).The standard of care for patients with submassive PE is to either receive anticoagulant therapy, EKOS (Catheter Assisted Thrombolysis) or thromboectomy. tPA is given at the FDA approved dose (100mg) occasionally at doses much higher than our study proposes. PatientS with PE will have the initial CTA, echocardiogram and lab work as standard of care. The follow up CTA is usually standard of care at Day 30 and the follow up echocardiograms are considered standard of care if the previous echocardiogram was abnormal.The study is being done as a proof of concept that low dose tPA is effective in clot lysis and will result in far less risk than the FDA dose. If our study achieves its aims, the research will advance clinical practices in treating pulmonary embolism by reporting the safety of lower dose tPA and opening opportunities to further explore the use of lower dose tPA to improve patient safety and outcomes.