Clinical trial NCT01531829: Low Dose Rt-PA for Acute Normotensive Pulmonary Embolism With RVD
Official title: Low Dose Rt-PA Plus LMWH Compared With LMWH Alone for the Treatment of Normotensive Pulmonary Embolism Patients With Acute RV Dysfunction: A Randomized，Multi-Center，Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pulmonary Thromboembolisms
Pulmonary Embolism
Keywords: pulmonary embolism
right ventricular dysfunction
Thrombolysis
Heparin
Lead sponsor: Beijing Chao Yang Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Technology of the People´s Republic of China
First posted: 2012-02-13
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: the composite end point of death from any cause or treatment failure,recurrence of VTE
timeFrame: 7 days
measure: improvements of right ventricular functions on echocardiogram and pulmonary artery obstruction on CT angiographs
timeFrame: 7 days
measure: serious life threatening bleeding such as cerebral hemorrhage and other major bleeding episodes
timeFrame: 7 days
measure: clinical relevant non-major bleedings
timeFrame: 7 days
Secondary outcomes:
measure: the composite end point of death from any cause or treatment failure,recurrence of VTE
timeFrame: 3 months and 6 months
measure: improvements of right ventricular functions on echocardiogram and pulmonary artery obstruction on CT angiographs
timeFrame: 3 months and 6 months
measure: serious life threatening bleeding such as cerebral hemorrhage and other major bleeding episodes
timeFrame: 3 months and 6 months
measure: clinical relevant non-major bleedings
timeFrame: 3 months and 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Daxing People's Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Fuwai Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital, Ministry of Health
state: Beijing
city: Bejing
country: China
facility: Beijing Chao Yang Hospial
state: Beijing
city: Guang Zhou
country: China
facility: The Third Affiliated Hospital of Zhongshan University in Guangzhou
state: GUang Dong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Zhongshan University in Guangzhou
state: Guangdong
city: Nan ning
country: China
facility: The Guangxi Zhuang Autonomous Region people's Hospital
state: Guangxi
city: Shenzhen
country: China
facility: Guangzhou Shenzhen People's Hospital
state: Guangzhou
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical College
state: Hebei
city: Handan
country: China
facility: The first hospital of Handan city Hebei Province
state: Hebei
city: Hengshui
country: China
facility: Hebei Hengshui international Heping Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Hebei Affiliated Hospital of North China Coal Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: Hebei Medical University Second Hospital
state: Hebei
city: Harbin
country: China
facility: No.2 Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Baotou
country: China
facility: The Third Affiliated Hospital of Inner Mongolia Medical College
state: Inner Mongolia
city: Hohhot
country: China
facility: Hospital of Inner Mongolia Autonomous Region
state: Inner Mongolia
city: Anshan
country: China
facility: Anshan Iron and Steel Company General Hospital
state: Liaoning
city: Dalian
country: China
facility: The first hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning General Hospital of Shenyang Military Region
state: Liaoning
city: Shenyang
country: China
facility: Shenyang Medical College affiliated Fengtian Hospital
state: Liaoning
city: Yinchuan
country: China
facility: Affiliated Hospital of Ningxia Medical University
state: Ningxia
city: Jining
country: China
facility: Shandong Jining Medical University Affiliated Hospital
state: Shandong
city: Qingdao
country: China
facility: Shandong Medical College Affiliated Hospital of Qiingdao University
state: Shandong
city: Yantai
country: China
facility: Shandong Yantai city Yantai Mountain hospital
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiao Tong University
state: Shanghai
city: Shanghai
country: China
facility: Second Military Medical University Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Shanghai Fudan University
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Medical University Second Hospital
state: Shanxi
city: Taiyuan
country: China
facility: The first hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: The Fourth Military Medical University, Xijing Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan University, West China Hospital
state: Sichuan
city: Urumqi
country: China
facility: The first hospital of Xinjiang Medical University
state: Xinjiang
city: Urumqi
country: China
facility: The Xinjiang Uygur Autonomous Region people's Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: Zhejiang Sir Run Run Shaw Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical College in Zhejiang
state: Zhejiang
Study officials:
affiliation: Beijing Chao Yang Hospital
name: Chen Wang, PhD,MD
role: PRINCIPAL_INVESTIGATOR
References: