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

• ClinicalTrials.gov Identifier: NCT03847883
• Recruitment Status: Completed
• First Posted: February 20, 2019
• Last Update Posted: February 20, 2019
• Sponsor: Rajavithi Hospital
• Collaborator: Lumpang Hospital
• Information provided by (Responsible Party): Dr Subsai Kongsaengdao, Rajavithi Hospital

Study Description

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

Condition or disease	Intervention/treatment	Phase
Acute Stroke	Drug: Intravenous Solution Ateplase	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 408 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: January 1, 2011
• Actual Primary Completion Date: December 31, 2018
• Actual Study Completion Date: February 14, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Death in 36 hours [ Time Frame: 0-36 hours ]
   Number of patient die in 36 hours
2. Death in 3 months [ Time Frame: 0-3 months ]
   Number of patient die in 3 months
3. Death in 4 months [ Time Frame: 0-4 months ]
   Number of patient die in 4 months
4. Total number of patients with mRS 0-1 at discharged [ Time Frame: 1day to <3 months ]
   Number of patients with mRS 0-1 at discharge 1day to 3 months interval
5. Total number of patients with mRS 0-1 at 3 months [ Time Frame: At 3 months ]
   Number of patients with mRS 0-1 at 3 months
6. Number of patients with All intra-cerebral hemorrhage (ICH) at 36 hours [ Time Frame: 0- 36 hours ]
   Total Intracerebral hemorrhage (ICH) including both Symptomatic ICH , and Asymptomatic ICH
7. Number of patients with All intra-cerebral hemorrhage (ICH) at 3 months [ Time Frame: 0-3 months ]
   Total Intracerebral hemorrhage (ICH) including both Symptomatic ICH , and Asymptomatic ICH
8. Number of patients with All Intra-cerebral hemorrhage (ICH) at 4months [ Time Frame: 0-4 months ]
   Total Intracerebral hemorrhage (ICH) including both Symptomatic ICH , and Asymptomatic ICH
9. Number of patients with Symptomatic Intra-cerebral hemorrhage (ICH) at 36 hours [ Time Frame: 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
10. Number of patients with Symptomatic Intra-cerebral hemorrhage (ICH) at 4 months [ Time Frame: 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
11. Number of patients with Asymptomatic Intra-cerebral hemorrhage (ICH) 36 hours [ Time Frame: 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
12. Number of patients with Asymptomatic Intra-cerebral hemorrhage (ICH) 3 months [ Time Frame: 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
13. Number of patients with Asymptomatic Intra-cerebral hemorrhage (ICH) 4 months [ Time Frame: 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 :

1. Good stroke outcomes [ Time Frame: 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

2. Improved mRS at discharge [ Time Frame: (At discharge) 1 day to 3 months ]
   Number of patients with improve mRS after treatment at least 1 Score
3. Improved mRS 3 months [ Time Frame: At 3 months ]
   Number of patients with improve mRS after treatment at least 1 Score
4. Number of patienta with Length of hospital stay (LOS) less than 7 days Days [ Time Frame: 1- 7 days ]
   Number of patients with LOS < 7 days ( patients must survive )
5. All complications [ Time Frame: 0-4 months ]
   Number of patients with stroke complications after treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Thailand

Assistant Professor Subsai Kongsaengdao

Bangkok, Thailand, 10400

Sponsors and Collaborators

Rajavithi Hospital

Lumpang Hospital

More Information

• Responsible Party: Dr Subsai Kongsaengdao, Associated Professor, Rajavithi Hospital
• ClinicalTrials.gov Identifier: NCT03847883
• Other Study ID Numbers: Rajavithi Lumphang 001 study
• First Posted: February 20, 2019
• Last Update Posted: February 20, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr Subsai Kongsaengdao, Rajavithi Hospital:

Ateplase; Intravenous recombinant tissue plasminogen activator; Acute is hemic stroke; Low-dose Ateplase; rtPa; Modified Rankin 's Scale

Additional relevant MeSH terms:

Stroke; Ischemic Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases