Brain Ischemia, Cerebral Infarction
Conditions
Keywords
acute stroke, thrombolytic therapy, tissue plasminogen activator
Brief summary
Based on previous studies comparing Duteplase\[a recombinant tissue plasminogen activator (rt-PA) very similar to alteplase\] doses, we performed a clinical trial with 0.6mg/kg, which is lower than the internationally approved dosage of 0.9mg/kg, aiming to assess the efficacy and safety of alteplase for the Japanese.
Detailed description
Based on previous studies comparing Duteplase ( an rt-PA very similar to alteplase) doses, we performed a clinical trial with 0.6mg/kg, which is lower than the internationally approved dosage of 0.9mg/kg, aiming to assess the efficacy and safety of alteplase for the Japanese. The primary endpoints were the rate of patients with mRS score of 0-1 at 3 months and the incidence of sICH within 36 hours. Thresholds for these endpoints were determined by calculating 90% confidence intervals of weighted averages derived from published reports. The protocol was defined according to the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA stroke study with slight modifications.
Interventions
DRUGAlteplase
0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour
Sponsors
Kyowa Hakko Kogyo Co., Ltd.
Tanabe Pharma Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with acute ischemic stroke within 3 hours of onset, with a clearly defined time of onset
Exclusion criteria
1. patients with rapidly improving neurological symptoms or with minor neurological deficit (National Institutes of Health Stroke Scale (NIHSS) score of ≤4) prior to the start of treatment 2. Computed Tomography (CT) evidence of non-minor early ischemic signs (minor early ischemic sign was defined as the involvement of one-third or less of the middle cerebral artery area) 3. CT evidence of cerebral hemorrhage or subarachnoid hemorrhage 4. symptoms suggestive of subarachnoid hemorrhage 5. lactation, pregnancy or suggestive pregnancy; menstruation 6. platelet count below 100,000/mm3 7. heparin administration within 48 hours preceding stroke onset with an elevated activated partial thromboplastin time (APTT); current use of oral anticoagulants with an International Normalized Ratio (INR) of ≥1.7; use of drugs not allowed to be administered concomitantly with alteplase (other thrombolytic agents, ozagrel sodium, argatroban and edaravone) prior to the study treatment 8. major surgery or serious trauma within the preceding 14 days; serious head or spinal cord trauma within the preceding 3 months 9. a history of gastrointestinal or urinary tract hemorrhage within the previous 21 days 10. arterial puncture at a noncompressible site within the preceding 7 days 11. a history of stroke within the preceding 3 months; a history of intracranial hemorrhage or increased risk of intracranial hemorrhage because of cerebral aneurysm, arteriovenous malformation, neoplasm, etc. 12. concurrent severe hepatic or renal dysfunction 13. malignant tumor under treatment 14. a systolic blood pressure of \>185 mmHg or diastolic blood pressure of \>110 mmHg 15. a need for aggressive treatment to reduce blood pressure to below these limits(14)) 16. blood glucose levels of \<50 mg/dL or \>400 mg/dL 17. acute myocardial infarction(AMI) or endocarditis after AMI 18. concurrent infectious endocarditis, moya-moya disease (Willis circle occlusion syndrome), aortic dissection, neck trauma, etc.; strong suspicion of ischemic cerebrovascular disorder caused by non-thrombotic occlusion or any other hemodynamic condition 19. seizure at the onset of stroke 20. coma (a Japan Coma Scale score of ≥100) 21. an mRS score of ≥2 before stroke onset 22. a history of hypersensitivity to protein preparations 23. difficulty in monitoring for 3 months 24. less than 3 months since any other clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 at 3 Months | at 3 months | The number of patients with a mRS score of 0-1. The mRS has 6 items, where 0 = No symptoms at all, 1 = No significant disability despite symptoms, 2 = Slight disability, 3 = Moderate disability, 4 = Moderately severe disability, 5 = Severe disability. The higher scores reflect increased disability. |
| Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours | within 36 hours | The number of patients with sICH |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alteplase 0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour | 103 |
| Total | 103 |
Baseline characteristics
| Characteristic | Alteplase |
|---|---|
| Age, Continuous | 70.9 years STANDARD_DEVIATION 9.8 |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 91 / 103 |
| serious Total, serious adverse events | 29 / 103 |
Outcome results
Primary
Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 at 3 Months
The number of patients with a mRS score of 0-1. The mRS has 6 items, where 0 = No symptoms at all, 1 = No significant disability despite symptoms, 2 = Slight disability, 3 = Moderate disability, 4 = Moderately severe disability, 5 = Severe disability. The higher scores reflect increased disability.
Time frame: at 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alteplase | Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 at 3 Months | 38 participants |
Primary
Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours
The number of patients with sICH
Time frame: within 36 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alteplase | Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours | 6 participants |