Low-dose Versus Standard Dose Alteplase in Acute Ischemic Stroke , 4 Monthes Prospective Study

Study Overview
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Brief Summary
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Cohort A Randomized Control trial of Ateplase 0.6, 0.75 and 0.9 mg/kg in 78 patients Cohort B single arm 0.9 mg/kg Ateplase in 330 patients Combined Cohort A and B evaluate different of death, intra-cerebral hemorrhage, numberof patient with mRS 0-1 at discharge and 3 months follow up, and other important stroke outcomes

Detailed Description
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We conducted the prospective study to compare the low-dose and standard-dose rtPa and identify the important factors predicted stroke outcomes in acute stroke patient received intravenous rtPa. In Cohort A, During 2011-2012, 78 patients were randomly assigned to received intravenous rtPa 0.6 mg/kg , 0.75 mg/Kg, or 0.9 mg/Kg (1:1:1). After interim analysis during 2012-2017, in Cohort B, 330 patients were assigned to receive standard-dose rtPa 0.9 mg/kg. The good outcomes were defined as improvement of modified Rankin scale (mRS) by final score 0-1 or improvement > 4 points at discharge or 3 months follow up, absent of intracranial hemorrhage within 36 hours treatment, 90-day post-stroke survival , and short hospital length of stay.

Official Title
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Low-dose Versus Standard-dose Ateplase in Acute Ischemic Stroke ; A 4 Months Prospective Randomized Control Pilot Follow by Single Arm Standard Dose Ateplase Study.

Conditions
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Acute Stroke

Intervention / Treatment
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* Drug: Intravenous Solution Ateplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Acute ischemic stroke Age 18 to 80 years Onset of stroke symptoms with in 4.5 hours before initiation of study-drug administration Stroke symptoms present for at least 30 minutes with no significant improvement before treatment Exclusion Criteria: patients with Intracranial hemorrhage the symptoms of Time onset was unknown Symptoms rapidly improving or only minor before start of infusion Seizure at the onset of stroke Stroke or serious head trauma within the previous 3 months Administration of heparin within the 48 hours preceding the onset of stroke, with an activate partial-thromboplastin time at presentation exceeding the upper limit of the normal range Platelet count of less than 100,000 per cubic millimeter Systole pressure greater than 185 mm Hg or diastole pressure greater than 110 mm Hg, or aggressive treatment intravenous medication) necessary to reduce blood pressure to these limits Blood glucose less than 50 mg per deciliter or greater than 400 mg per deciliter Symptoms suggestive of subarachnoid hemorrhage, even if CT scan was normal Oral anticoagulant treatment Major surgery or severe trauma within the previous 3 months Other major disorders associated with an increased risk of bleeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cohort A double blind Randomized controlled trial 0.6 or 0.7 or 0.9 mg/Kg Ateplase in78 patients (preliminary) Cohort B single arm standard dose 0.9 mg/kg Ateplase in 330 patients
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 0.6 mg/kg Ateplase<br>Low dose 0.6 mg/kg Ateplase injection with in 4.5 Hr after onset of stroke (n = 26 in cohort A) | Drug: Intravenous Solution Ateplase<br>* Infusion Low dose 0.6 or 0.75 or 0.9 mg/kg Ateplase injection iv bolus 10% of total dose and infusion 90% of total dose in1 hour , with in 4.5Hr after onset of stroke<br>|
| Active Comparator: 0.75 mg/kg Ateplase<br>Low dose 0.75 mg/kg Ateplase injection with in 4.5 Hr after onset of stroke(n = 26 in cohort A) | Drug: Intravenous Solution Ateplase<br>* Infusion Low dose 0.6 or 0.75 or 0.9 mg/kg Ateplase injection iv bolus 10% of total dose and infusion 90% of total dose in1 hour , with in 4.5Hr after onset of stroke<br>|
| Active Comparator: 0.9 mg/kg Ateplase<br>Low dose 0.9 mg/kg Ateplase injection with in 4.5 Hr after onset of stroke(n = 26 in cohort A and n= 330 in Cohort B) | Drug: Intravenous Solution Ateplase<br>* Infusion Low dose 0.6 or 0.75 or 0.9 mg/kg Ateplase injection iv bolus 10% of total dose and infusion 90% of total dose in1 hour , with in 4.5Hr after onset of stroke<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death in 36 hours | Number of patient die in 36 hours | 0-36 hours | 
| Death in 3 months | Number of patient die in 3 months | 0-3 months | 
| Death in 4 months | Number of patient die in 4 months | 0-4 months | 
| Total number of patients with mRS 0-1 at discharged | Number of patients with mRS 0-1 at discharge 1day to 3 months interval | 1day to <3 months | 
| Total number of patients with mRS 0-1 at 3 months | Number of patients with mRS 0-1 at 3 months | At 3 months | 
| Number of patients with All intra-cerebral hemorrhage (ICH) at 36 hours | Total Intracerebral hemorrhage (ICH) including both Symptomatic ICH , and Asymptomatic ICH | 0- 36 hours | 
| Number of patients with All intra-cerebral hemorrhage (ICH) at 3 months | Total Intracerebral hemorrhage (ICH) including both Symptomatic ICH , and Asymptomatic ICH | 0-3 months | 
| Number of patients with All Intra-cerebral hemorrhage (ICH) at 4months | Total Intracerebral hemorrhage (ICH) including both Symptomatic ICH , and Asymptomatic ICH | 0-4 months | 
| Number of patients with Symptomatic Intra-cerebral hemorrhage (ICH) at 36 hours | Total Number of patients with Symptomatic ICH need emergency surgery craniotomy or Venticulostomy drainaged or other management to reduce intracranial pressure such as intubation with mechanical ventilator or hyperosmolar drug administration | 0-36 hours | 
| Number of patients with Symptomatic Intra-cerebral hemorrhage (ICH) at 4 months | Total Number of patients with Symptomatic ICH need emergency surgery craniotomy or Venticulostomy drainaged or other management to reduce intracranial pressure such as intubation with mechanical ventilator or hyperosmolar drug administration | 0-4 months | 
| Number of patients with Asymptomatic Intra-cerebral hemorrhage (ICH) 36 hours | Total Number of patients with Asymptomatic ICH wich no need emergency surgery craniotomy or Venticulostomy drainaged or other management to reduce intracranial pressure such as intubation with mechanical ventilator or hyperosmolar drug administration | 0-36 hours | 
| Number of patients with Asymptomatic Intra-cerebral hemorrhage (ICH) 3 months | Total Number of patients with Asymptomatic ICH wich no need emergency surgery craniotomy or Venticulostomy drainaged or other management to reduce intracranial pressure such as intubation with mechanical ventilator or hyperosmolar drug administration | 0-3 months | 
| Number of patients with Asymptomatic Intra-cerebral hemorrhage (ICH) 4 months | Total Number of patients with Asymptomatic ICH wich no need emergency surgery craniotomy or Venticulostomy drainaged or other management to reduce intracranial pressure such as intubation with mechanical ventilator or hyperosmolar drug administration | 0-4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Good stroke outcomes | Total number of patients with good outcomes were defined as number of patients with this any one item criteria improvement of modified Rankin scale (mRS) by final score 0-1 mRS improvement > 4 points at discharge or 3 months follow up, And must full fill all of this criteria 1) absent of intracranial hemorrhage within 36 hours treatment and 2) survive at 90-day post-stroke ,and 3) short hospital length of stay less than 7 days | 0-4 months | 
| Improved mRS at discharge | Number of patients with improve mRS after treatment at least 1 Score | (At discharge) 1 day to 3 months | 
| Improved mRS 3 months | Number of patients with improve mRS after treatment at least 1 Score | At 3 months | 
| Number of patienta with Length of hospital stay (LOS) less than 7 days Days | Number of patients with LOS < 7 days ( patients must survive ) | 1- 7 days | 
| All complications | Number of patients with stroke complications after treatment | 0-4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ateplase, Intravenous recombinant tissue plasminogen activator, Acute is hemic stroke, Low-dose Ateplase, rtPa, Modified Rankin 's Scale