A Phase II Clinical Study to Evaluate the Efficacy and Safety of Thrombolytic Therapy With Recombinant Human Tissue-type Plasminogen Activator Derivative for Acute Pulmonary Embolism
Overview
- Phase
- Phase 2
- Intervention
- Recombinant human tissue-type plasminogen activator derivative
- Conditions
- Acute Pulmonary Embolism
- Sponsor
- Angde Biotech Pharmaceutical Co., Ltd.
- Enrollment
- 174
- Primary Endpoint
- the opening rate of thrombus
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this trial is to compare the efficacy and safety of Recombinant Human Tissue-Type Plasminogen Activator Derivative(rPA) and Recombinant Tissue-Type Plasminogen Activator(rt-PA) for the treatment of acute pulmonary embolism.
This trial includes two stages, the first stage is to study the dosage of administration of the test drug(rPA), the second is to compare the efficacy and safety of rPA and rt-PA. Both of the two stages are randomized, open and parallel controlled.
Detailed Description
This trial is a multicenter, randomized, open and parallel controlled project designed for patients with acute pulmonary embolism requiring thrombolysis after anticoagulant therapy in high-risk and middle-high risk populations. For the first stage: Subjects who are qualified for the screening criteria according to the inclusion and exclusion criteria will be randomly assigned to low-dose test drugs, high-dose test drugs or reference drugs for thrombolytic therapy at a ratio of 1:1:1. For the second stage: Subjects who are qualified for the screening criteria according to the inclusion and exclusion criteria will be randomly assigned to rPA(test group)or rt-PA(control group) for thrombolytic therapy at a ratio of 1:1.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with high-risk acute pulmonary embolism: the main manifestations are shock and hypotension.Systemic systolic blood pressure \<90 millimetre of mercury (mmHg) (1mmHg=0.133kPa), or a decrease from the base value ≥40 millimetre of mercury for more than 15min.
- •Patients with moderate to high-risk acute pulmonary embolism who have worsened anticoagulant therapy require thrombolytic therapy:
- •(Patients with moderate to high-risk acute pulmonary embolism: Right ventricular dysfunction (RVD) and elevated cardiac biomarkers coexist.)
- •RVD diagnostic criteria: imaging evidence including echocardiography or CT:1) Ultrasound examination is consistent with the following performance:
- •right ventricular dilatation (right ventricular end-diastolic diameter / left ventricular end-diastolic diameter \> 1.0 or 0.9);
- •right ventricular free wall movement amplitude decreased;
- •tricuspid regurgitation speed increased;
- •tricuspid annulus systolic displacement decreased (\<17mm); 2) Computed Tomographic Pulmonary Angiography examination meets the following conditions: right ventricular dilatation (right ventricular end-diastolic diameter / left ventricular end-diastolic diameter \> 1.0 or 0.9) found at the four-chamber heart level;
- •Cardiac biological markers including N terminal pro B type natriuretic peptide (NT-proBNP/BNP) and troponin elevation;
- •Diagnostic criteria for worsening after anticoagulant therapy in patients with moderate to high risk acute pulmonary embolism:
Exclusion Criteria
- •a history of hemorrhagic stroke or unexplained stroke;
- •Ischemic stroke or transient ischemic attack within 3 months;
- •Central nervous system damage or tumor;
- •Surgery and trauma of the brain or spine within 2 months;
- •Active internal bleeding within 1 month (such as gastrointestinal bleeding, hemoptysis, blood in the stool, etc.);
- •High risk of bleeding: evidence or history of bleeding disorders, bleeding tendency, bleeding constitution or coagulopathy;
- •oral anticoagulant (can be randomized after a certain period of time, such as oral rivaroxaban can be randomized after 1 day of elution, oral warfarin can be performed at International Normalized Ratio \<2.0 random);
- •1 week after pregnancy or delivery;
- •vascular puncture of the site that cannot be oppressed;
- •Cardiopulmonary resuscitation within 10 days;
Arms & Interventions
low dose group
Recombinant human tissue-type plasminogen activator derivative(rPA) for injection: 18 mg, Intravenous injection for 2 minutes or more. A separate venous access should be used for bolus injection,a common venous access shared with other drugs is not allowed for injection. And no other drugs mixed with test drug during the injection.
Intervention: Recombinant human tissue-type plasminogen activator derivative
high dose group
Recombinant human tissue-type plasminogen activator derivative (rPA) for injection: the first injection of 18 mg rPA is pushed slowly for 2 minutes or more,the second injection of 9mg rtPA is pushed for 1 minute or more.The interval between the two injections should be controlled accurately about 30 minutes. A separate venous access should be used for bolus injection,a common venous access shared with other drugs is not allowed for injection. And no other drugs mixed with test drug during the injection.
Intervention: Recombinant human tissue-type plasminogen activator derivative
comparative group
Recombinant tissue plasminogen activator for injection: continuous intravenous injection for 2 hours.
Intervention: Recombinant human tissue-type plasminogen activator
Outcomes
Primary Outcomes
the opening rate of thrombus
Time Frame: 48 hours (Day 3)after injection
The pulmonary artery occlusion index is calculated according to Qanadli scores. There are 10 segmental arteries in each pulmonary artery (3 in the upper lobes, 2 in the middle or lingual arteries, and 5 in the inferior lobes), 1 segment of arterial partial obstruction is 1 point, complete obstruction is 2 points, and the total score is divided by 40 (the total score of complete obstruction of bilateral pulmonary arteries) is the pulmonary artery obstruction index. Thrombus opening rate is calculated by the Qanadli CT embolization index, the formula is as follows: improvement (%) = (significant improvement cases + mild improvement cases) / overall number of cases, significant improvement = Qanadli CT embolization index decreased from baseline ≥ 75%; mild improvement = Qanadli CT embolization index decreased by ≥25% and \<75% from baseline; unchanged = Qanadli CT embolization index decreased \<25% from baseline; deterioration = Qanadli CT embolization index increased from baseline.
Secondary Outcomes
- Mortality and recurrence rate(within 7 days after injection)
- The incidence rates of endpoint events(within 30 days after injection)
- the ratio of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter(Day 2 (24h), Day 3 (48h), Day 7, Day 30 after injection)
- The ratio of N terminal pro B type natriuretic peptide/B-type natriuretic peptide(Day 2 (24h), Day 3 (48h), Day 7, Day 30 after injection)
- Thrombotic load(Day 3（48h）、Day 30 after injection)
- the opening rate of thrombus(Day 30 after injection)
- the occurrence rate of adverse event(through study completion, an average of 1.5 year)
- blood pressure(through study completion, an average of 1.5 year)
- life signs(through study completion, an average of 1.5 year)
- pulse(through study completion, an average of 1.5 year)
- Hemoglobin(through study completion, an average of 1.5 year)
- red blood cell(through study completion, an average of 1.5 year)
- white blood cell(through study completion, an average of 1.5 year)
- platelet(through study completion, an average of 1.5 year)