Injection of Recombinant Human Tissue-type Plasminogen Activator Derivative for Acute Pulmonary Embolism(rPA)

NCT04110275 | Unknown Phase 2 DMC

• 1 other identifier: CRAD-RTL-203
• Study Type: interventional
• Target: 174
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Pulmonary Embolism

Keywords

Acute Pulmonary Embolism

Outcome Measures

Primary Outcomes (1)

• the opening rate of thrombus

  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.

  48 hours (Day 3)after injection

Secondary Outcomes (14)

• 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

Study Arms (3)

low dose group

EXPERIMENTAL

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.

Drug: Recombinant human tissue-type plasminogen activator derivative

high dose group

EXPERIMENTAL

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.

Drug: Recombinant human tissue-type plasminogen activator derivative

comparative group

ACTIVE COMPARATOR

Recombinant tissue plasminogen activator for injection: continuous intravenous injection for 2 hours.

Drug: Recombinant human tissue-type plasminogen activator

Interventions

Recombinant human tissue-type plasminogen activator derivative DRUG

Recombinant human tissue-type plasminogen activator derivative(rPA,chemical name: Reteplase,brand name:Ruitongli) 18mg/10ml/stick, provided by AngDe Biotech Pharmaceutical Co.,LIMITED(LTD)

Also known as: Ruitongli

high dose group; low dose group

Recombinant human tissue-type plasminogen activator DRUG

Recombinant human tissue-type plasminogen activator(rt-PA,chemical name:Alteplase,brand name: Actilyse)50mg/stick,provided by Boehringer Ingelheim Pharma Gesellschaft mit beschrankter Haftung(GmbH)\&Co,

Also known as: Actilyse

comparative group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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: 1. right ventricular dilatation (right ventricular end-diastolic diameter / left ventricular end-diastolic diameter \> 1.0 or 0.9); 2. right ventricular free wall movement amplitude decreased; 3. tricuspid regurgitation speed increased; 4. 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:
• Hemodynamic deterioration (defined as meeting at least one of the following conditions: 1. requires cardiopulmonary resuscitation; 2. systemic systolic blood pressure \<90 mmHg (1 mmHg = 0.133 kPa), or a decrease in basal value ≥ 40 mmHg for more than 15 min, or with terminal Low organ perfusion (limb cold or urine volume \<30 ml/hr, or mental confusion); 3. need to infuse a booster drug (except dopamine \<5 μg/kg/min) to maintain adequate tissue perfusion and systolic blood pressure \> 90 mmHg ;
• The time from onset to the time of thrombolysis is ≤ 14 days;
• Male patients must agree to take effective contraceptive measures during treatment and at least 28 days after the end of the trial, and do not donate sperm during this period; women of childbearing age must be negative within the first 72 hours of randomization, and agree to adopt effective contraceptive measures during treatment and at least 28 days afterwards the last treatment.
• Voluntary signing of written informed consent form.

You may not qualify if:

• 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);
• week after pregnancy or delivery;
• vascular puncture of the site that cannot be oppressed;
• Cardiopulmonary resuscitation within 10 days;
• Hypertension that is difficult to control (systolic blood pressure \> 180 mmHg and / or diastolic blood pressure ≥ 110 mmHg);
• Liver function is grade C of Child-Pugh ;
• Infective endocarditis;
• History of aneurysms or arteriovenous malformations, or suspected aortic dissection;
• Cardiac thrombosis;

Sponsors & Collaborators

• Angde Biotech Pharmaceutical Co., Ltd.: lead

MeSH Terms

Interventions

Tissue Plasminogen Activator

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• zhenguo Zhai, Doctor

  China-Japan Friendship Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

yongbiao xu, Manager

CONTACT

008615163577213; xuyongbiao2@crbiopharm.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: observers are masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2019
• First Posted: October 1, 2019
• Study Start: October 1, 2019
• Primary Completion: May 1, 2021
• Study Completion: August 1, 2021
• Last Updated: October 11, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share