Low Dose Rt-PA for Acute Normotensive Pulmonary Embolism With RVD
- Conditions
- Pulmonary ThromboembolismsPulmonary Embolism
- Interventions
- Drug: Low Molecular Weight HeparinDrug: Recombinant tissue plasminogen activator (rt-PA)
- Registration Number
- NCT01531829
- Lead Sponsor
- Beijing Chao Yang Hospital
- Brief Summary
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).
- Detailed 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 460
-
18 y≤Age≤75y
-
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
-
Hemodynamic stability, diastolic pressure>90mmHg.
-
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
- RV anterior wall thickness > 5mm confirmed by echocardiography
- Active internal bleeding and spontaneous intracranial hemorrhage in preceding 6 months
- Major surgery, organ biopsy or non-compressible punctures within 2 weeks
- Ischemic stroke occurred within 2 months
- Gastrointestinal bleeding within 10 days
- Severe trauma occurred within15 days
- Neurosurgery or eye surgery within 1 months
- Severe hypertension difficult to control (systolic blood pressure>180mmHg or diastolic blood pressure>110mmHg)
- Cardiopulmonary resuscitation
- Platelet count less than 100×109 / L
- Pregnancy, or within 2 week post partum
- Infective endocarditis; left atrial thrombus; aneurysm
- Serious liver and kidney dysfunction
- Diabetic hemorrhagic retinopathy
- Suffering with bleeding disorders
- Chronic thromboembolic pulmonary hypertension
- Moderate to severe chronic obstructive pulmonary disease (COPD).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LMWH Low Molecular Weight Heparin Low molecular weight heparin Low dose (50mg/2h) rt-PA plus LMWH Recombinant tissue plasminogen activator (rt-PA) Low dose (50mg/2h) recombinant tissue plasminogen activator (rt-PA) plus low molecular weight heparin(LMWH)regimen
- Primary Outcome Measures
Name Time Method the composite end point of death from any cause or treatment failure,recurrence of VTE 7 days improvements of right ventricular functions on echocardiogram and pulmonary artery obstruction on CT angiographs 7 days clinical relevant non-major bleedings 7 days serious life threatening bleeding such as cerebral hemorrhage and other major bleeding episodes 7 days
- Secondary Outcome Measures
Name Time Method the composite end point of death from any cause or treatment failure,recurrence of VTE 3 months and 6 months improvements of right ventricular functions on echocardiogram and pulmonary artery obstruction on CT angiographs 3 months and 6 months serious life threatening bleeding such as cerebral hemorrhage and other major bleeding episodes 3 months and 6 months clinical relevant non-major bleedings 3 months and 6 months
Trial Locations
- Locations (35)
Beijing Chao Yang Hospial
🇨🇳Bejing, Beijing, China
Beijing Daxing People's Hospital
🇨🇳Beijing, Beijing, China
Beijing Fuwai Hospital
🇨🇳Beijing, Beijing, China
Beijing Hospital, Ministry of Health
🇨🇳Beijing, Beijing, China
The Guangxi Zhuang Autonomous Region people's Hospital
🇨🇳Nan ning, Guangxi, China
Affiliated Hospital of Chengde Medical College
🇨🇳Chengde, Hebei, China
The first hospital of Handan city Hebei Province
🇨🇳Handan, Hebei, China
Hebei Hengshui international Heping Hospital
🇨🇳Hengshui, Hebei, China
The First Affiliated Hospital of Zhongshan University in Guangzhou
🇨🇳Guangzhou, Guangdong, China
Hebei Affiliated Hospital of North China Coal Medical University
🇨🇳Shijiazhuang, Hebei, China
Hebei Medical University Second Hospital
🇨🇳Shijiazhuang, Hebei, China
No.2 Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
The Third Affiliated Hospital of Inner Mongolia Medical College
🇨🇳Baotou, Inner Mongolia, China
Hospital of Inner Mongolia Autonomous Region
🇨🇳Hohhot, Inner Mongolia, China
Anshan Iron and Steel Company General Hospital
🇨🇳Anshan, Liaoning, China
The first hospital of Dalian Medical University
🇨🇳Dalian, Liaoning, China
Shandong Jining Medical University Affiliated Hospital
🇨🇳Jining, Shandong, China
Shandong Medical College Affiliated Hospital of Qiingdao University
🇨🇳Qingdao, Shandong, China
Shenyang Medical College affiliated Fengtian Hospital
🇨🇳Shenyang, Liaoning, China
Affiliated Hospital of Ningxia Medical University
🇨🇳Yinchuan, Ningxia, China
Shandong Yantai city Yantai Mountain hospital
🇨🇳Yantai, Shandong, China
Shanxi Medical University Second Hospital
🇨🇳Taiyuan, Shanxi, China
The first hospital of Shanxi Medical University
🇨🇳Taiyuan, Shanxi, China
The Fourth Military Medical University, Xijing Hospital
🇨🇳Xi'an, Shanxi, China
Sichuan University, West China Hospital
🇨🇳Chengdu, Sichuan, China
The first hospital of Xinjiang Medical University
🇨🇳Urumqi, Xinjiang, China
The Xinjiang Uygur Autonomous Region people's Hospital
🇨🇳Urumqi, Xinjiang, China
Ruijin Hospital Affiliated to Shanghai Jiao Tong University
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Wenzhou Medical College in Zhejiang
🇨🇳Wenzhou, Zhejiang, China
Second Military Medical University Changhai Hospital
🇨🇳Shanghai, Shanghai, China
The Third Affiliated Hospital of Zhongshan University in Guangzhou
🇨🇳Guang Zhou, GUang Dong, China
Guangzhou Shenzhen People's Hospital
🇨🇳Shenzhen, Guangzhou, China
Liaoning General Hospital of Shenyang Military Region
🇨🇳Shenyang, Liaoning, China
Zhejiang Sir Run Run Shaw Hospital
🇨🇳Hangzhou, Zhejiang, China
Zhongshan Hospital Affiliated to Shanghai Fudan University
🇨🇳Shanghai, Shanghai, China