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

Pulmonary Embolism Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01531829
• Other study ID #: BJCYH1893
• Status: Recruiting
• Phase: Phase 4
• First received: February 9, 2012
• Last updated: February 11, 2012
• Start date: July 2009
• Est. completion date: December 2012

Study information

• Verified date: February 2012
• Source: Beijing Chao Yang Hospital
• Contact: Chen Wang, PhD,MD
• Phone: 8610-85231893
• Email: cyh-birm[@]263.net
• Is FDA regulated: No
• Health authority: China: Ministry of Science and Technology
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 460
• Est. completion date: December 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism
• Pulmonary Thromboembolisms
• Thromboembolism

Intervention

Drug:
• Recombinant tissue plasminogen activator (rt-PA)
Low dose (50mg/2h) rt-PA plus LMWH
• Low Molecular Weight Heparin
0.1ml/10kg,q12h,5-7 days

Locations

Country	Name	City	State
China	Anshan Iron and Steel Company General Hospital	Anshan	Liaoning
China	The Third Affiliated Hospital of Inner Mongolia Medical College	Baotou	Inner Mongolia
China	Beijing Daxing People's Hospital	Beijing	Beijing
China	Beijing Fuwai Hospital	Beijing	Beijing
China	Beijing Hospital, Ministry of Health	Beijing	Beijing
China	Beijing Chao Yang Hospial	Bejing	Beijing
China	Affiliated Hospital of Chengde Medical College	Chengde	Hebei
China	Sichuan University, West China Hospital	Chengdu	Sichuan
China	The first hospital of Dalian Medical University	Dalian	Liaoning
China	The Third Affiliated Hospital of Zhongshan University in Guangzhou	Guang Zhou	GUang Dong
China	The First Affiliated Hospital of Zhongshan University in Guangzhou	Guangzhou	Guangdong
China	The first hospital of Handan city Hebei Province	Handan	Hebei
China	Zhejiang Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
China	No.2 Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Hebei Hengshui international Heping Hospital	Hengshui	Hebei
China	Hospital of Inner Mongolia Autonomous Region	Hohhot	Inner Mongolia
China	Shandong Jining Medical University Affiliated Hospital	Jining	Shandong
China	The Guangxi Zhuang Autonomous Region people's Hospital	Nan ning	Guangxi
China	Shandong Medical College Affiliated Hospital of Qiingdao University	Qingdao	Shandong
China	Ruijin Hospital Affiliated to Shanghai Jiao Tong University	Shanghai	Shanghai
China	Second Military Medical University Changhai Hospital	Shanghai	Shanghai
China	Zhongshan Hospital Affiliated to Shanghai Fudan University	Shanghai	Shanghai
China	Liaoning General Hospital of Shenyang Military Region	Shenyang	Liaoning
China	Shenyang Medical College affiliated Fengtian Hospital	Shenyang	Liaoning
China	Guangzhou Shenzhen People's Hospital	Shenzhen	Guangzhou
China	Hebei Affiliated Hospital of North China Coal Medical University	Shijiazhuang	Hebei
China	Hebei Medical University Second Hospital	Shijiazhuang	Hebei
China	Shanxi Medical University Second Hospital	Taiyuan	Shanxi
China	The first hospital of Shanxi Medical University	Taiyuan	Shanxi
China	The first hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	The Xinjiang Uygur Autonomous Region people's Hospital	Urumqi	Xinjiang
China	The First Affiliated Hospital of Wenzhou Medical College in Zhejiang	Wenzhou	Zhejiang
China	The Fourth Military Medical University, Xijing Hospital	Xi'an	Shanxi
China	Shandong Yantai city Yantai Mountain hospital	Yantai	Shandong
China	Affiliated Hospital of Ningxia Medical University	Yinchuan	Ningxia

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Chao Yang Hospital	Ministry of Science and Technology of the People´s Republic of China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the composite end point of death from any cause or treatment failure,recurrence of VTE		7 days	No
Primary	improvements of right ventricular functions on echocardiogram and pulmonary artery obstruction on CT angiographs		7 days	No
Primary	serious life threatening bleeding such as cerebral hemorrhage and other major bleeding episodes		7 days	Yes
Primary	clinical relevant non-major bleedings		7 days	Yes
Secondary	the composite end point of death from any cause or treatment failure,recurrence of VTE		3 months and 6 months	No
Secondary	improvements of right ventricular functions on echocardiogram and pulmonary artery obstruction on CT angiographs		3 months and 6 months	No
Secondary	serious life threatening bleeding such as cerebral hemorrhage and other major bleeding episodes		3 months and 6 months	Yes
Secondary	clinical relevant non-major bleedings		3 months and 6 months	Yes