Japan Alteplase Clinical Trial (J-ACT): Efficacy and Safety Study of Tissue Plasminogen Activator (Alteplase) for Ischemic Stroke
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Alteplase 0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour |
Drug: Alteplase
0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour
|
Outcome Measures
Primary Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
Patients with acute ischemic stroke within 3 hours of onset, with a clearly defined time of onset
Exclusion Criteria:
-
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
-
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)
-
CT evidence of cerebral hemorrhage or subarachnoid hemorrhage
-
symptoms suggestive of subarachnoid hemorrhage
-
lactation, pregnancy or suggestive pregnancy; menstruation
-
platelet count below 100,000/mm3
-
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
-
major surgery or serious trauma within the preceding 14 days; serious head or spinal cord trauma within the preceding 3 months
-
a history of gastrointestinal or urinary tract hemorrhage within the previous 21 days
-
arterial puncture at a noncompressible site within the preceding 7 days
-
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.
-
concurrent severe hepatic or renal dysfunction
-
malignant tumor under treatment
-
a systolic blood pressure of >185 mmHg or diastolic blood pressure of >110 mmHg
-
a need for aggressive treatment to reduce blood pressure to below these limits(14))
-
blood glucose levels of <50 mg/dL or >400 mg/dL
-
acute myocardial infarction(AMI) or endocarditis after AMI
-
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
-
seizure at the onset of stroke
-
coma (a Japan Coma Scale score of ≥100)
-
an mRS score of ≥2 before stroke onset
-
a history of hypersensitivity to protein preparations
-
difficulty in monitoring for 3 months
-
less than 3 months since any other clinical trial
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Cardiovascular Center | Suita | Osaka | Japan | 565-8565 |
Sponsors and Collaborators
- Mitsubishi Tanabe Pharma Corporation
- Kyowa Hakko Kogyo Co., Ltd.
Investigators
- Study Chair: Takenori Yamaguchi, MD, National Cerebral and Cardiovascular Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 527-0110
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Alteplase |
|---|---|
| Arm/Group Description | 0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour |
| Period Title: Overall Study | |
| STARTED | 103 |
| COMPLETED | 103 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Alteplase |
|---|---|
| Arm/Group Description | 0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour |
| Overall Participants | 103 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
70.9
(9.8)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
39
37.9%
|
| Male |
64
62.1%
|
Outcome Measures
| Title | Number of Patients With a Modified Rankin Scale (mRS) Score of 0-1 at 3 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Alteplase |
|---|---|
| Arm/Group Description | 0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour |
| Measure Participants | 103 |
| Number [participants] |
38
36.9%
|
| Title | Number of Patients With Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours |
|---|---|
| Description | The number of patients with sICH |
| Time Frame | within 36 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Alteplase |
|---|---|
| Arm/Group Description | 0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour |
| Measure Participants | 103 |
| Number [participants] |
6
5.8%
|
Adverse Events
| Time Frame | 3 Months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Alteplase | |
| Arm/Group Description | 0.6mg/kg intravenous alteplase with 10% being administered as a bolus followed by continuous infusion of the remainder over 1 hour | |
All Cause Mortality |
||
| Alteplase | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Alteplase | ||
| Affected / at Risk (%) | # Events | |
| Total | 29/103 (28.2%) | |
| Blood and lymphatic system disorders | ||
| Disseminated intravascular coagulation | 1/103 (1%) | |
| Cardiac disorders | ||
| Acute myocardial infarction | 1/103 (1%) | |
| Atrial fibrillation | 1/103 (1%) | |
| Atrioventricular block complete | 1/103 (1%) | |
| Cardiac failure NOS | 1/103 (1%) | |
| Ventricular arrhythmia NOS | 1/103 (1%) | |
| Infections and infestations | ||
| Infection staphylococcal | 1/103 (1%) | |
| Pneumonia NOS | 2/103 (1.9%) | |
| Injury, poisoning and procedural complications | ||
| Brain herniation | 1/103 (1%) | |
| Femoral neck fracture | 1/103 (1%) | |
| Tracheal obstruction | 1/103 (1%) | |
| Traumatic haematoma | 1/103 (1%) | |
| Investigations | ||
| C-reactive protein increased | 1/103 (1%) | |
| Platelet count decreased | 1/103 (1%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Left atrial myxoma | 1/103 (1%) | |
| Metastases to peritoneum | 1/103 (1%) | |
| Nervous system disorders | ||
| Brain oedema | 3/103 (2.9%) | |
| Carotid artery dissection | 1/103 (1%) | |
| Cerebral haemorrhage | 3/103 (2.9%) | |
| Cerebral infarction | 7/103 (6.8%) | |
| Haemorrhagic cerebral infarction | 2/103 (1.9%) | |
| Intracranial haemorrhage NOS | 1/103 (1%) | |
| Subdural hygroma | 1/103 (1%) | |
| Psychiatric disorders | ||
| Depression | 1/103 (1%) | |
| Renal and urinary disorders | ||
| Renal failure NOS | 1/103 (1%) | |
| Renal impairment NOS | 1/103 (1%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Asthma aggravated | 1/103 (1%) | |
| Pneumonia aspiration | 2/103 (1.9%) | |
| Vascular disorders | ||
| Atherosclerosis obliterans | 1/103 (1%) | |
Other (Not Including Serious) Adverse Events |
||
| Alteplase | ||
| Affected / at Risk (%) | # Events | |
| Total | 91/103 (88.3%) | |
| Cardiac disorders | ||
| Atrial fibrillation | 7/103 (6.8%) | |
| Ventricular extrasystoles | 10/103 (9.7%) | |
| Gastrointestinal disorders | ||
| Diarrhoea NOS | 14/103 (13.6%) | |
| Gastrointestinal haemorrhage NOS | 6/103 (5.8%) | |
| Periproctitis | 6/103 (5.8%) | |
| Vomiting NOS | 14/103 (13.6%) | |
| General disorders | ||
| Pyrexia | 15/103 (14.6%) | |
| Hepatobiliary disorders | ||
| Hepatic function abnormal NOS | 7/103 (6.8%) | |
| Infections and infestations | ||
| Pneumonia NOS | 8/103 (7.8%) | |
| Urinary tract infection NOS | 16/103 (15.5%) | |
| Nervous system disorders | ||
| Haemorrhagic cerebral infarction | 37/103 (35.9%) | |
| Headache NOS | 15/103 (14.6%) | |
| Renal and urinary disorders | ||
| Haematuria | 8/103 (7.8%) | |
| Neurogenic bladder | 7/103 (6.8%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Hiccups | 6/103 (5.8%) | |
| Nasopharyngitis | 14/103 (13.6%) | |
| Skin and subcutaneous tissue disorders | ||
| Haemorrhage subcutaneous | 22/103 (21.4%) | |
| Contusion | 7/103 (6.8%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Clinical Trials, Information Desk |
|---|---|
| Organization | Mitsubishi Tanabe Pharma Corporation |
| Phone | |
| cti-inq-ml@ml.mt-pharma.co.jp |
- 527-0110