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To evaluate the safety and efficacy of alteplase when administered between 3 and 4.5 hours after onset of stroke symptoms in Chinese patients with acute ischemic stroke
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| alteplase | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| alteplase | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Percentage of Patients With Modified Rankin Scale (mRS 0-1) (Favourable Outcome) Response at Day 90 After Stroke Onset by Face-to-face Interview With Patient | The percentage of patients with modified Rankin Scale (mRS 0-1) (favourable outcome) response at Visit 5 (Day 90) after stroke onset by face-to-face interview with patient. Modified Rankin Scale (mRS): 0 = no symptom at all, 1 = no significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = dead. | 90 days |
| The Percentage of Patients With Symptomatic Intracranial Haemorrhage (sICH) Centrally Evaluated by Data-monitoring Committee (DMC) Consultants According to European Cooperative Acute Stroke Study (ECASS) III Definition Within the Whole Study Period | The percentage of patients with symptomatic intracranial haemorrhage (sICH) centrally evaluated by data-monitoring committee (DMC) consultants according to European Cooperative Acute Stroke Study (ECASS) III definition within the whole study period. According to the protocol, sICH (ECASS III criteria) was defined as: any apparently extravascular blood in the brain or within the cranium that was associated with clinical deterioration (defined by an increase in the NIHSS score of 4 or more points), or that led to death and that was identified as the predominant cause of the neurological deterioration. sICH event was firstly evaluated by investigator. The DMC consultants evaluated all the patients with NIHSS score increase of at least 4 any time after treatment (including all fatal patients and sICH events evaluated by investigator). Wilson score confidence interval is presented. | 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| The Percentage of Global Outcome Responder at Day 90 if he/She Obtains the Following Results at Day 90 (for All of the 4 Endpoints) mRS Score of 0 to 1; Barthel Index Score >= 95; NIHSS Score of 0 to 1; Glasgow Outcome Scale Score of 1 | Percentage of global outcome responder at day 90 if he/she obtains the following results at day 90 for the endpoints mRS score of 0 to 1; Barthel Index score >= 95; NIHSS score of 0 to 1; Glasgow Outcome Scale score of 1. mRS: 0 = no symptom at all, 1 = no significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = dead. NIHSS is composed of 11 items, and for each item a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. Glasgow Outcome Score applies to patients with brain damage allowing the objective assessment of their recovery in five categories: 1 Good Recovery, 2 Moderately Disabled, 3 Severely Disabled, 4 Vegetative State, 5 Dead. Barthel Index score to measure performance in activities of daily living with the scale ranging from 0 to 100. Global outcome response is the intersection of above four respective outcomes. |
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Inclusion criteria:
Age >= 18 years at screening(visit 1A) but <= 80 years Signed and dated written informed consent in accordance with good clinical practice and local legislation prior to admission to the trial Diagnosis of ischemic stroke with a measureable neurological deficit on National Institute of Health Stroke Scale (NIHSS) Thrombolytic therapy can be initiated within 3 to 4.5 hours of stroke onset Further inclusion criteria apply
Exclusion criteria:
Evidence of intracranial haemorrhage (ICH) on the (Computer Tomography) CT/(Magnetic Resonance Imaging)MRI-scan or symptoms suggestive of subarachnoid haemorrhage, even if the CT/MRI-scan is normal Acute bleeding diathesis Severe stroke as assessed clinically( e.g. National Institute of Health Stroke Scale>25) and/ or imaging demonstrates multi-lobar infarction (hypodensity >1/3 cerebral hemisphere) Severe uncontrolled arterial hypertension, e.g. systolic blood pressure>185 mmHg or diastolic blood pressure>110mmHg, or aggressive management (intravenous medication) necessary to reduce blood pressure to these limits Blood glucose <50mg/ dL or >400 mg/dL Any history of prior stroke in previous 3 months, or any history of prior stroke with concomitant diabetes Seizure at stroke onset Further exclusion criteria apply
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Tiantan Hospital affiliated to Cap Med University | Beijing | 100050 | China | |||
| First Hospital of Jilin University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32467323 | Derived | Zheng H, Yang Y, Chen H, Li C, Chen Y, Shi FD, Yang L, Cui X, Lu Z, Liang Y, Cui S, Xu A, Wu Y, Sun Y, Wang Y. Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: the first multicentre, phase III trial in China. Stroke Vasc Neurol. 2020 Sep;5(3):285-290. doi: 10.1136/svn-2020-000337. Epub 2020 May 28. |
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All patients were screened for eligibility to participate in the trial. Patients attended a specialist sites which ensured that they met all strictly implemented inclusion/exclusion criteria. Patients were not to be entered to trial if any one of the specific entry criteria was violated. Rescue medication was allowed for all patients as required.
A total of 121 patients were screened from 11 centres across China. Of the screened patients, 1 patient did not meet the study entry criteria. The first patient visit was on 12 December 2016 and the last patient visit was on 11 December 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Alteplase (Rt-PA) | Patients were administered single dose of Alteplase (rt-PA) 0.9 milligram/kilogram (mg/kg) (with an upper limit of 90 milligram (mg)), ten percent of the total dose was administered as a bolus over 1 - 2 minutes. The remaining 90% of the dose was given by continuous intravenous (IV) infusion over 60 minutes if there was no evidence of an allergic reaction within 5 minutes following the administration of the test dose. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 15, 2017 | Dec 10, 2018 |
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| 90 days |
| Patient Survival Probability at Visit 5 (Censoring at Day 90) | Patient survival probability at visit 5 (censoring at day 90). The percentage of patients who died until Day 1, Day 7, Day 30, Day 90. | 90 days |
| The Percentage of Patients With Death Related to Stroke or of Neurological Causes | The percentage of patients with death related to stroke or of neurological causes. | 90 days |
| The Percentage of Patients With Severity of Adverse Events | The percentage of patients with severity of adverse events (AEs). The percentage of patients with different categories of AEs are presented. | On-treatment period, that is, within 7 days from the start of bolus |
| The Percentage of Patients With Incidence of Cerebral Herniation and Symptomatic Edema | The percentage of patients with incidence of cerebral herniation and symptomatic edema. | 90 days |
| Changchun |
| 130031 |
| China |
| Dongguan People's Hospital | Dongguan | 523059 | China |
| No.900 Hospital of PLA Joint Logistics Support Force | Fuzhou | 350025 | China |
| Third Affiliated Hospital of Guangzhou Medical University | Guangzhou | 510150 | China |
| The First Affiliated Hospital of Jinan University | Guangzhou | 510630 | China |
| General Hospital of Shenyang Military Region | Shenyang | 110015 | China |
| Tianjin Medical University General Hospital | Tianjin | 300052 | China |
| Renmin Hospital of Wuhan University | Wuhan | 430060 | China |
| Xuzhou Central Hospital | Xuzhou | 221009 | China |
| Yanbian University Hospital | Yanji | 133000 | China |
| COMPLETED |
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| NOT COMPLETED |
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|
Treated Set (TS) consisted of all enrolled patients who received study medication at any dose.
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| ID | Title | Description |
|---|---|---|
| BG000 | Alteplase (Rt-PA) | Patients were administered single dose of Alteplase (rt-PA) 0.9 milligram/kilogram (mg/kg) (with an upper limit of 90 milligram (mg)), ten percent of the total dose was administered as a bolus over 1 - 2 minutes. The remaining 90% of the dose was given by continuous intravenous (IV) infusion over 60 minutes if there was no evidence of an allergic reaction within 5 minutes following the administration of the test dose. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Treated Set | Mean | Standard Deviation | Years |
| ||||||||||||||||
| Sex: Female, Male | Treated Set | Count of Participants | Participants |
| |||||||||||||||||
| Ethnicity (NIH/OMB) | Treated Set | Count of Participants | Participants |
| |||||||||||||||||
| Race (NIH/OMB) | Treated Set | Count of Participants | Participants |
| |||||||||||||||||
| Baseline NIHSS | Baseline scores based on National Institute of Health Stroke Scale (NIHSS). The NIHSS is composed of 11 items, and for each item a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score ranges from 0 to 42. Severe stroke as assessed clinically (e.g., NIHSS >25). | Treated Set | Mean | Standard Deviation | Unit on Scale |
| |||||||||||||||
| Baseline NIHSS by class | Number of participants at baseline scores based on National Institute of Health Stroke Scale (NIHSS) by class. The NIHSS is composed of 11 items, and for each item a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score ranges from 0 to 42. Severe stroke as assessed clinically (e.g., NIHSS >25). | Treated Set | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Percentage of Patients With Modified Rankin Scale (mRS 0-1) (Favourable Outcome) Response at Day 90 After Stroke Onset by Face-to-face Interview With Patient | The percentage of patients with modified Rankin Scale (mRS 0-1) (favourable outcome) response at Visit 5 (Day 90) after stroke onset by face-to-face interview with patient. Modified Rankin Scale (mRS): 0 = no symptom at all, 1 = no significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = dead. | Treated Set, worst and last observation carried forward were used for the imputation of efficacy endpoints | Posted | Number | Percentage of patients | 90 days |
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| Secondary | The Percentage of Global Outcome Responder at Day 90 if he/She Obtains the Following Results at Day 90 (for All of the 4 Endpoints) mRS Score of 0 to 1; Barthel Index Score >= 95; NIHSS Score of 0 to 1; Glasgow Outcome Scale Score of 1 | Percentage of global outcome responder at day 90 if he/she obtains the following results at day 90 for the endpoints mRS score of 0 to 1; Barthel Index score >= 95; NIHSS score of 0 to 1; Glasgow Outcome Scale score of 1. mRS: 0 = no symptom at all, 1 = no significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = dead. NIHSS is composed of 11 items, and for each item a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. Glasgow Outcome Score applies to patients with brain damage allowing the objective assessment of their recovery in five categories: 1 Good Recovery, 2 Moderately Disabled, 3 Severely Disabled, 4 Vegetative State, 5 Dead. Barthel Index score to measure performance in activities of daily living with the scale ranging from 0 to 100. Global outcome response is the intersection of above four respective outcomes. | Treated Set, worst and last observation carried forward were used for the imputation of efficacy endpoints | Posted | Number | 95% Confidence Interval | Percentage of patients | 90 days |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | The Percentage of Patients With Symptomatic Intracranial Haemorrhage (sICH) Centrally Evaluated by Data-monitoring Committee (DMC) Consultants According to European Cooperative Acute Stroke Study (ECASS) III Definition Within the Whole Study Period | The percentage of patients with symptomatic intracranial haemorrhage (sICH) centrally evaluated by data-monitoring committee (DMC) consultants according to European Cooperative Acute Stroke Study (ECASS) III definition within the whole study period. According to the protocol, sICH (ECASS III criteria) was defined as: any apparently extravascular blood in the brain or within the cranium that was associated with clinical deterioration (defined by an increase in the NIHSS score of 4 or more points), or that led to death and that was identified as the predominant cause of the neurological deterioration. sICH event was firstly evaluated by investigator. The DMC consultants evaluated all the patients with NIHSS score increase of at least 4 any time after treatment (including all fatal patients and sICH events evaluated by investigator). Wilson score confidence interval is presented. | Treated Set | Posted | Number | 95% Confidence Interval | Percentage of patients | 90 days |
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| Secondary | Patient Survival Probability at Visit 5 (Censoring at Day 90) | Patient survival probability at visit 5 (censoring at day 90). The percentage of patients who died until Day 1, Day 7, Day 30, Day 90. | Treated Set | Posted | Number | Percentage of patients | 90 days |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | The Percentage of Patients With Death Related to Stroke or of Neurological Causes | The percentage of patients with death related to stroke or of neurological causes. | Treated Set | Posted | Number | 95% Confidence Interval | Percentage of patients | 90 days |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | The Percentage of Patients With Severity of Adverse Events | The percentage of patients with severity of adverse events (AEs). The percentage of patients with different categories of AEs are presented. | Treated Set | Posted | Number | Percentage of patients | On-treatment period, that is, within 7 days from the start of bolus |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | The Percentage of Patients With Incidence of Cerebral Herniation and Symptomatic Edema | The percentage of patients with incidence of cerebral herniation and symptomatic edema. | Treated Set | Posted | Number | 95% Confidence Interval | Percentage of patients | 90 days |
|
|
Serious and Other Adverse Events (AEs): From the administration of trial medication until 7 days, up to 7 days. All-Cause Mortality: From the administration of trial medication until 100 days, up to 100 days
There is 1 patient died during the post-study period (Day 100) which is not relevant to study medication. But this patient has been counted in this table.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Alteplase (Rt-PA) | Patients were administered single dose of Alteplase (rt-PA) 0.9 milligram/kilogram (mg/kg) (with an upper limit of 90 milligram (mg)), ten percent of the total dose was administered as a bolus over 1 - 2 minutes. The remaining 90% of the dose was given by continuous intravenous (IV) infusion over 60 minutes if there was no evidence of an allergic reaction within 5 minutes following the administration of the test dose. | 7 | 120 | 12 | 120 | 72 | 120 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute left ventricular failure | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Brain herniation | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Stroke in evolution | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
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| Hyperhomocysteinaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
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| Lung infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 20.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
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| Cerebral artery stenosis | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Cerebrovascular stenosis | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 23, 2017 | Dec 10, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D020521 | Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D010959 | Tissue Plasminogen Activator |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D010960 | Plasminogen Activators |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| 10-15 |
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| 16-20 |
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| >20 |
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| Title | Measurements |
|---|---|
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| Moderate disability |
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| Moderate Severe disability |
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| Severe disability |
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| Dead |
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