A PhaseⅡ of Injection for Recombinant Human Tissue Plasminogen Kinase Derivative in Treatment of Acute Ischemic Stroke.

NCT04028518 | Unknown Phase 2

• 1 other identifier: CRAD-RTL-202
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this trial is to compare the efficacy of different doses of investigator product and comparator product in patients with acute ischemic stroke in 4.5 Hours after stroke onset, and provide a basis of drug administration for phase Ⅲ clinical trial. The secondary purpose of this trial is to compare the safety of different dose of investigational product and comparator product in patients with acute ischemic stroke in 4.5 hours afterstroke onset .

Conditions

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• The proportion of subjects with NIHSS score ≤1 or the decrease of 4 points or more from the baseline on the 14th day after treatment;

  The National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The range of scores is from 0 (normal) to 42 (profound effect of stroke on patient).

  on the 14th day after treatment

Secondary Outcomes (5)

• The proportion of subjects with NIHSS score ≤1 or the decrease of 4 points or more from the baseline at 72 hours after treatment;

  at 72 hours after treatment;

• The proportion of subjects with mRS score of 0-1 on the 30th day and 90th day after treatment;

  on the 30th day and 90th day after treatment;

• The proportion of subjects with mRS score of 0-2 on the 30th day and 90th day after treatment;

  on the 30th day and 90th day after treatment;

• Continuous changes of mRS scores on the 30th and 90th days after treatment;

  on the 30th and 90th days after treatment;

• The proportion of subjects with Barthel index score≥95 on the 30th day and 90th day after treatment;

  on the 30th day and 90th day after treatment;

Other Outcomes (3)

• Percentage of subjects with symptomatic intracranial hemorrhage (sICH);

  within 36h after thrombolysis

• Mortality within 90 days after treatment;

  within 90 days after treatment;

• The Proportion of subjects with adverse events/serious adverse events within 90 days after treatment.

  within 90 days after treatment

Study Arms (3)

The high-dose group

EXPERIMENTAL

Experimental: r-PA Dose: stick 18 mg; Mode of admin: The high-dose group (18 mg + 18 mg) was divided into two intravenous injections. the first intravenous bolus injection of 18mg,after 30mins, the second intravenous bolus injection of 18 mg, Push slowly for more than 2mins each time.Subjects were closely monitored during the medication and within 24 hours of administration.

Drug: r-PA

The low-dose group

EXPERIMENTAL

Experimental: r-PA Dose: stick 18 mg; Mode of admin: The low-dose group (12 mg + 12 mg) was divided into two intravenous injections, the first intravenous bolus injection of 12 mg, after 30mins, the second intravenous bolus injection of 12 mg, Push slowly for more than 2mins each time.Subjects were closely monitored during the medication and within 24 hours of administration.

Drug: r-PA

Active Comparator: Alteplase

EXPERIMENTAL

Active Comparator: Alteplase Drug: Alteplase for Injection Dose:50mg;20mg Mode of admin: 0.9 mg/kg (maximum dose of 90 mg) intravenous, 10% of which was injected intravenously within the first 1min, and the rest continued intravenous infusion for 1 h. Subjects should be closely monitored during the treatment period and within 24 hours of medication.Subjects were monitored according to the "Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China 2018".

Drug: Alteplase for Injection

Interventions

r-PA DRUG

Drug: r-PA Dose: stick 18 mg; Mode of admin: The high-dose group (18 mg + 18 mg) was divided into two intravenous injections. the first intravenous bolus injection of 18mg,after 30mins, the second intravenous bolus injection of 18 mg, Push slowly for more than 2mins each time.

Also known as: Recombinant Human Tissue Plasminogen Kinase Derivative for Injection

The high-dose group

Alteplase for Injection DRUG

Drug: Alteplase for Injection Dose:50mg; 20mg Mode of admin: 0.9 mg/kg (maximum dose of 90 mg) intravenous, 10% of which was injected intravenously within the first 1min, and the rest continued intravenous infusion for 1 h.

Also known as: Recombinant Human Tissue Plasminogen Active for Injection

Active Comparator: Alteplase

Eligibility Criteria

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

You may qualify if:

• Diagnosis of acute ischemic stroke according to the WHO (World Health Organization) stroke diagnostic criteria, and symptoms of stroke have existed for at least 30mins, and there is no significant improvement before treatment；
• The symptoms of acute ischemic stroke are expected to be less than 4.5 hours after the time of acute ischemic stroke which is defined as the last time the patient function well;
• NIHSS score at the time of treatment: from 4 points to 24 points (including 4 points and 24 points);
• From the signing of informed consent form to 3 months of the last dose should be the absence of a birth plan and willing to take effective contraceptive measures;
• Understand and follow the research process, voluntarily participate, and sign an informed consent form (informed consent is voluntarily signed by the person or legal representative).

You may not qualify if:

• Weight \>120kg;
• Imaging shows multiple cerebral infarction (low density \> 1/3 brain hemisphere);
• The timing of stroke symptoms is not known;
• mRS score before stroke≥ 2 points;
• NIHSS score 1a (level of consciousness) ≥ 2 points during screening;
• CT/MRI imaging examination showed signs of intracranial hemorrhage or suspected subarachnoid hemorrhage despite CT/MRI imaging findings did not show abnormalities.
• Subjects have an acute bleeding tendency, including a platelet count of less than 100 × 109 / L, application of heparin or oral anticoagulant drugs (such as warfarin) within 24 hours before onset , and an INR \> 1.6;
• Patients who are ready to go or have undergone endovascular treatment;
• Patients who had severe trauma or major surgery in the last 3 months (according to the investigator's assessment);
• A stroke has occurred in the last 3 months; or has a history of any stroke with diabetes;
• Severe liver damage, including liver failure, cirrhosis, portal hypertension (esophageal varices), and active hepatitis;
• Other diseases lead to patients with an expected survival time of no more than one year;
• Hypertension remains uncontrolled after active antihypertensive therapy. Uncontrolled hypertension refers to a systolic blood pressure \>185 mmHg and/or a diastolic blood pressure \>110 mmHg measured at intervals of at least 10mins, repeated 3 times;
• Blood glucose \<50 mg/dl (equivalent to 2.78mmol/L) or \>400 mg/dl (equivalent to 22.2mmol/L);
• Patients who are unable to cooperate or are unwilling to cooperate with epileptic seizures, or other mental illnesses during stroke episodes;

Sponsors & Collaborators

• Angde Biotech Pharmaceutical Co., Ltd.: lead
• Beijing Tiantan Hospital: collaborator

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100055, China

Location

Related Publications (1)

• Li S, Wang X, Jin A, Liu G, Gu H, Li H, Campbell BCV, Fisher M, Yang Y, Wei Y, Wang J, Wang Y, Zhao X, Liu L, Li Z, Meng X, Wang Y. Safety and Efficacy of Reteplase Versus Alteplase for Acute Ischemic Stroke: A Phase 2 Randomized Controlled Trial. Stroke. 2024 Feb;55(2):366-375. doi: 10.1161/STROKEAHA.123.045193. Epub 2023 Dec 28.

  PMID: 38152962 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Injections; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; 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

Central Study Contacts

YongJun Wang, Professor

CONTACT

+8613911172565; yongjunwang1962@gmail.com

Study Design

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

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: July 22, 2019
• Study Start: July 20, 2019
• Primary Completion: October 31, 2020
• Study Completion: March 31, 2021
• Last Updated: July 22, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)