Low Dosage of rt-PA in the Treatment of Pulmonary Thromboembolism in China

This study has been completed.
Sponsor:
Information provided by:
Beijing Chao Yang Hospital
ClinicalTrials.gov Identifier:
NCT00781378
First received: October 21, 2008
Last updated: October 28, 2008
Last verified: October 2008
  Purpose

Recombinant tissue plasminogen activator (rt-PA) is currently the most commonly used thrombolytic drug in patients with pulmonary thromboembolism (PTE). Optimal dosing with maximal benefits and minimal risks is of great importance. Considering the lower body weight in general Chinese population, we compared the efficacy and safety of lower dose rt-PA 50mg/2h regimen with the FDA-approved rt-PA 100mg/2h regimen in selected PTE patients.


Condition Intervention Phase
Pulmonary Embolism
Thromboembolism
Drug: rt-PA
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety Evaluation of Low Dosage of Recombinant Tissue Plasminogen Activator (rt-PA) in the Treatment of Pulmonary Thromboembolism: A Multi-Center, Randomized Controlled Trial in China

Resource links provided by NLM:


Further study details as provided by Beijing Chao Yang Hospital:

Primary Outcome Measures:
  • The improvement of the right hart function on echocardiograms [ Time Frame: within the 1st 14 days ] [ Designated as safety issue: No ]
  • Perfusion defect score of lung V/Q scans [ Time Frame: within the 1st 14 days ] [ Designated as safety issue: No ]
  • Quantitative computed tomographic pulmonary angiography (CTPA) score on 2d, 14d after treatment. [ Time Frame: within the 1st 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Major or minor bleeding [ Time Frame: within 1st 14 days ] [ Designated as safety issue: Yes ]
  • PE recurrence [ Time Frame: within the 1st 14 days ] [ Designated as safety issue: Yes ]
  • Death [ Time Frame: within the 1st 14 days ] [ Designated as safety issue: Yes ]

Enrollment: 118
Study Start Date: June 2002
Study Completion Date: February 2006
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1
rt-PA 100 mg continuous intravenous infusion for 2 hours
Drug: rt-PA
rt-PA 100 mg continuous intravenous infusion for 2 hours
Other Name: Recombinant tissue plasminogen activator
Experimental: group 2
rt-PA 50 mg continuous intravenous infusion for 2 hours
Drug: rt-PA
rt-PA 50 mg continuous intravenous infusion for 2 hours
Other Name: Recombinant tissue plasminogen activator

Detailed Description:

Pulmonary thromboembolism (PTE) is a severe and common clinical problem with substantial morbidity and mortality both in US and in Europe. Used to be considered as a rare disease in China, PTE has been increasingly diagnosed in recent years due to the increased awareness and the improvement of imaging techniques. PTE is life threatening without proper intervention at the early onset. Effective treatment can decrease the mortality and the complication of chronic thromboembolic pulmonary hypertension (CTEPH).

Recombinant tissue-type plasminogen activator (rt-PA) is currently the most commonly used drug for PTE thrombolysis. Like most thrombolytic medications, rt-PA carries a risk of significant bleeding, which is dose dependent. Thus, optimal dosing that can maximize benefits and minimize risks is of great importance. There is substantial controversy and debate regarding the optimal rt-PA dosage for thrombolytic therapy and whether the same dose should be used in all patients. Low dose of intravenous rt-PA for thrombolysis after acute myocardial infarction (AMI) had been suggested by previous studies. Experimental and clinical studies have indicated that a lower dose of rt-PA bolus may be potentially safer, and yet equally effective then the 2-h 100 mg rt-PA continuous infusion for PTE.

Considering lower body weight in Chinese population, a lower dose of 50mg rt-PA/2h may exhibit similar efficacy and safety as 100mg/2-h rt-PA for treating acute PTE in this population. We, therefore, compared these two regimens in a multi-center, randomized, controlled trial. The efficacy was assessed by the improvement of the right ventricular function on echocardiograms, perfusion defect score of lung V/Q scans or quantitative computed tomographic (CT) evaluation, safety was evaluated by incidence of major or minor bleeding, death rate, and PTE recurrence on 24h,14d after treatment.

110 patients will be randomized in the study. The patients included in the study will be randomized, in a double blind fashion, to receive rt-PA 100mg 2h (55 patients) or rt-PA50mg 2h(55 patients).Study treatment should be administered within 72 hours from echocardiography. Echocardiography will be repeated at 24 hours and 14 days from rt-PA injection. A Follow-up visit at 14 days from randomization will include: clinical history, physical examination and ECG and an echocardiographic examination CTPA and V/Q scan.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age between 18 and 75
  • symptomatic PE confirmed by: a high probability ventilation-perfusion lung scanning (V/Q scan) or the presence of intraluminal filling defect on spiral computed tomographic pulmonary angiography (CTPA)
  • PTE patients with haemodynamic instability, or cardiogenic shock
  • anatomic obstruction more than 2 lobes on CTPA, or defect more than 7 segments on V/Q scan combined with evidence of right ventricular dysfunction(RVD) and pulmonary hypertension on echocardiography
  • written informed consent

Exclusion Criteria:

  • active bleeding or spontaneous intracranial hemorrhage
  • major surgery, organ biopsy or recent puncture of a non-compressible vessel less than 10 days
  • cerebral arterial thrombosis within 2 months
  • gastro-intestinal bleeding within 10 days
  • major trauma within the past 15 days
  • neurosurgery or ophthalmologic operation with 30 days
  • uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg)
  • recent external cardiac resuscitation manoeuvres
  • platelet count < 100 000/mm3 at admission
  • pregnancy, puerperium or lactation with 2 weeks
  • infectious pericarditis or endocarditis
  • severe hepatic and kidney dysfunction
  • hemorrhagic retinopathy due to diabetes
  • a known bleeding disorder
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00781378

  Show 23 Study Locations
Sponsors and Collaborators
Beijing Chao Yang Hospital
Investigators
Principal Investigator: Chen WANG, Prof Beijing Institute of Respiratory Medicine,Beijing Chao-Yang Hospital,Capital Medical University
  More Information

Publications:
Responsible Party: Chen WANG, Beijing Chao-Yang Hospital
ClinicalTrials.gov Identifier: NCT00781378     History of Changes
Other Study ID Numbers: 2001BA703B13, 2004BA703B07
Study First Received: October 21, 2008
Last Updated: October 28, 2008
Health Authority: China: Ethics Committee

Keywords provided by Beijing Chao Yang Hospital:
Thrombolytic therapy
Recombinant tissue plasminogen activator
Efficacy
Safety

Additional relevant MeSH terms:
Thromboembolism
Pulmonary Embolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Lung Diseases
Respiratory Tract Diseases
Embolism
Plasminogen
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on October 19, 2014