Low Dose Rt-PA for Acute Normotensive Pulmonary Embolism With RVD

Capital Medical University

Status and phase: Unknown; Phase 4

Conditions: Pulmonary Embolism; Pulmonary Thromboembolisms

Treatments: Drug: Recombinant tissue plasminogen activator (rt-PA); Drug: Low Molecular Weight Heparin

Study type: Interventional

Funder types: Other

Identifiers

NCT01531829

BJCYH1893

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 460 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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460 participants in 2 patient groups

Low dose (50mg/2h) rt-PA plus LMWH

Experimental group

Description:

Low dose (50mg/2h) recombinant tissue plasminogen activator (rt-PA) plus low molecular weight heparin(LMWH)regimen

Treatment:

Drug: Recombinant tissue plasminogen activator (rt-PA)

LMWH

Active Comparator group

Description:

Low molecular weight heparin

Treatment:

Drug: Low Molecular Weight Heparin