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

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.

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

Study Overview

• Status: Completed
• Conditions: Acute Stroke
• Intervention / Treatment: Drug: Intravenous Solution Ateplase

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 408
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Assistant Professor Subsai Kongsaengdao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of Acute ischemic stroke
2. Age 18 to 80 years
3. Onset of stroke symptoms with in 4.5 hours before initiation of study-drug administration
4. Stroke symptoms present for at least 30 minutes with no significant improvement before treatment

Exclusion Criteria:

1. patients with Intracranial hemorrhage
2. the symptoms of Time onset was unknown
3. Symptoms rapidly improving or only minor before start of infusion
4. Seizure at the onset of stroke
5. Stroke or serious head trauma within the previous 3 months
6. Administration of heparin within the 48 hours preceding the onset of stroke, with an activate
7. partial-thromboplastin time at presentation exceeding the upper limit of the normal range
8. Platelet count of less than 100,000 per cubic millimeter
9. 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
10. Blood glucose less than 50 mg per deciliter or greater than 400 mg per deciliter
11. Symptoms suggestive of subarachnoid hemorrhage, even if CT scan was normal
12. Oral anticoagulant treatment
13. Major surgery or severe trauma within the previous 3 months
14. Other major disorders associated with an increased risk of bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 0.6 mg/kg Ateplase; 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; 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
Active Comparator: 0.75 mg/kg Ateplase; 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; 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
Active Comparator: 0.9 mg/kg Ateplase; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rajavithi Hospital
• Collaborators: Lumpang Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): February 14, 2019

Study Registration Dates

• First Submitted: February 15, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Ateplase; Intravenous recombinant tissue plasminogen activator; Acute is hemic stroke; Low-dose Ateplase; rtPa; Modified Rankin 's Scale
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: Rajavithi Lumphang 001 study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No