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

Phase 4

Completed

• Conditions: Acute Stroke
• Interventions: Drug: Intravenous Solution Ateplase

• Registration Number: NCT03847883
• Lead Sponsor: Rajavithi Hospital

Brief Summary

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

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 Timeline

• Study Start: 2011-01-01
• Primary Completion: 2018-12-31
• Status Verified: 2019-02
• Study Completion: 2019-02-14
• Study First Submitted: 2019-02-15
• Study First Submitted QC: 2019-02-19
• Last Update Submitted: 2019-02-19
• Study First Posted: 2019-02-20
• Last Update Posted: 2019-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 408

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
0.6 mg/kg Ateplase	Intravenous Solution Ateplase	Low dose 0.6 mg/kg Ateplase injection with in 4.5 Hr after onset of stroke (n = 26 in cohort A)
0.9 mg/kg Ateplase	Intravenous Solution 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)
0.75 mg/kg Ateplase	Intravenous Solution Ateplase	Low dose 0.75 mg/kg Ateplase injection with in 4.5 Hr after onset of stroke(n = 26 in cohort A)

Primary Outcome Measures

Name	Time	Method
Death in 3 months	0-3 months	Number of patient die in 3 months
Total number of patients with mRS 0-1 at discharged	1day to <3 months	Number of patients with mRS 0-1 at discharge 1day to 3 months interval
Number of patients with Asymptomatic Intra-cerebral hemorrhage (ICH) 36 hours	0-36 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
Total number of patients with mRS 0-1 at 3 months	At 3 months	Number of patients with mRS 0-1 at 3 months
Number of patients with All intra-cerebral hemorrhage (ICH) at 36 hours	0- 36 hours	Total Intracerebral hemorrhage (ICH) including both Symptomatic ICH , and Asymptomatic ICH
Number of patients with Symptomatic Intra-cerebral hemorrhage (ICH) at 36 hours	0-36 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
Number of patients with Symptomatic Intra-cerebral hemorrhage (ICH) at 4 months	0-4 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
Death in 36 hours	0-36 hours	Number of patient die in 36 hours
Death in 4 months	0-4 months	Number of patient die in 4 months
Number of patients with All intra-cerebral hemorrhage (ICH) at 3 months	0-3 months	Total Intracerebral hemorrhage (ICH) including both Symptomatic ICH , and Asymptomatic ICH
Number of patients with All Intra-cerebral hemorrhage (ICH) at 4months	0-4 months	Total Intracerebral hemorrhage (ICH) including both Symptomatic ICH , and Asymptomatic ICH
Number of patients with Asymptomatic Intra-cerebral hemorrhage (ICH) 3 months	0-3 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
Number of patients with Asymptomatic Intra-cerebral hemorrhage (ICH) 4 months	0-4 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

Secondary Outcome Measures

Name	Time	Method
Improved mRS 3 months	At 3 months	Number of patients with improve mRS after treatment at least 1 Score
Improved mRS at discharge	(At discharge) 1 day to 3 months	Number of patients with improve mRS after treatment at least 1 Score
Good stroke outcomes	0-4 months	Total number of patients with "good outcomes" were defined as number of patients with this any one item criteria; 1. improvement of modified Rankin scale (mRS) by final score 0-1; 2. 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
Number of patienta with Length of hospital stay (LOS) less than 7 days Days	1- 7 days	Number of patients with LOS \< 7 days ( patients must survive )
All complications	0-4 months	Number of patients with stroke complications after treatment

Trial Locations

Locations (1)

Assistant Professor Subsai Kongsaengdao; 🇹🇭 Bangkok, Thailand