Low Dose Rt-PA for Acute Normotensive Pulmonary Embolism With RVD
Low Dose Rt-PA for Acute Normotensive Pulmonary Embolism With RVD
In selected patients with acute pulmonary embolism(PE), low dose (50mg/2h) recombinant tissue
 plasminogen activator (rt-PA) regimen had been reported to have less bleeding tendency than
 the FDA-approved rt-PA 100mg/2h regimen 100mg/2h regimen (3% vs.10%), it is worthwhile to
 reveal whether low dose rt-PA plus low molecular weight heparin (LMWH) can rapidly reverses
 RV pressure overload in PE, but not increase bleeding and other adverse events. The aim of
 the study is to compare thrombolytic treatment with LMWH in patients with acute normotensive
 PE with right ventricular dysfunction(RVD).
In acute pulmonary embolism (PE), normotensive patients with acute RV dysfunction on
 echocardiography or computed tomography and with myocardial troponin elevation may have an
 adverse outcome. Thrombolysis rapidly reverses RV pressure overload in PE, but it increases
 the possibility of bleeding and it remains unclear whether it may improve the early or
 long-term clinical outcome of these selected normotensive patients.

 In our previous study, we found that low dose (50mg/2h) recombinant tissue plasminogen
 activator (rt-PA) regimen had less bleeding tendency than the 100mg/2h regimen (3% vs.10%),
 it is worthwhile to reveal whether low dose rt-PA plus Low Molecular Weight Heparin (LMWH)
 can rapidly reverses RV pressure overload in PE, but not increase bleeding and other adverse
 events.

 In this prospective, multicenter, randomized, control study, we compare low dose rt-PA plus
 LMWH vs. LMWH alone in acute normotensive pulmonary embolism patients with RV dysfunction.
 The primary efficacy outcome is the composite of death from any cause or treatment failure,
 improvements of right ventricular functions on echocardiogram and pulmonary artery
 obstruction on CT angiographs within 7 days of randomization. Second efficacy outcome is the
 recurrence of pulmonary embolism and deep venous thrombosis. Safety outcomes include serious
 life threatening bleeding such as cerebral hemorrhage and other major bleeding episodes, also
 include mild bleeding. In addition, 90-day clinical and echocardiographic follow-up will be
 performed, the recurrence of pulmonary embolism and deep venous thrombosis will be recorded.
 The study is expected to enroll approximately 460 patients.

 By determining the benefits vs risks of Low dose rt-PA plus LMWH compared with LMWH alone for
 the treatment in submassive or intermediate-risk PE, this trial is expected to reveal the
 worth of Low dose rt-PA plus LMWH treatment and what kind of PE patients are suitable for
 thrombolysis.
Inclusion Criteria:

 1. 18 y≤Age≤75y

 2. Acute PE (first symptoms occurred 14 d or less before randomization) confirmed by lung
 scan, or a positive computed tomographic pulmonary angiogram, or a positive selective
 pulmonary angiogram

 3. Hemodynamic stability, diastolic pressure>90mmHg.

 4. RV dysfunction confirmed by echocardiography (≥1 criterion), except left-side heart
 disease, congenital heart disease and mitral valve disease.

 -  Increase of the right ventricle showed presented with RV end-diastolic
 anteroposterior diameter >25 mm, Right/left ventricular end-diastolic diameter >1
 (apical or subcostal 4-chamber view) or Right/left ventricular end-diastolic
 anteroposterior diameter >0.5

 -  Hypokinesis of RV-free wall (range of motion less than 5 mm)

 -  Tricuspid regurgitation pressure >30mmHg

 Exclusion Criteria:

 1. RV anterior wall thickness > 5mm confirmed by echocardiography

 2. Active internal bleeding and spontaneous intracranial hemorrhage in preceding 6 months

 3. Major surgery, organ biopsy or non-compressible punctures within 2 weeks

 4. Ischemic stroke occurred within 2 months

 5. Gastrointestinal bleeding within 10 days

 6. Severe trauma occurred within15 days

 7. Neurosurgery or eye surgery within 1 months

 8. Severe hypertension difficult to control (systolic blood pressure>180mmHg or diastolic
 blood pressure>110mmHg)

 9. Cardiopulmonary resuscitation

 10. Platelet count less than 100×109 / L

 11. Pregnancy, or within 2 week post partum

 12. Infective endocarditis; left atrial thrombus; aneurysm

 13. Serious liver and kidney dysfunction

 14. Diabetic hemorrhagic retinopathy

 15. Suffering with bleeding disorders

 16. Chronic thromboembolic pulmonary hypertension

 17. Moderate to severe chronic obstructive pulmonary disease (COPD).