Tenecteplase Versus Alteplase in Ischemic Stroke Management (TALISMAN)

Sponsor

Reza Behrouz, DO (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02180204

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a double-blind parallel arm randomized trial aimed to assess efficacy and safety of intravenous Tenecteplase compared to intravenous Alteplase in eligible patients who present with symptoms of acute ischemic stroke within 3 to 4.5 hours from onset.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: Tenecteplase Drug: Alteplase	Phase 2/Phase 3

Detailed Description

Patients presenting with symptoms of acute ischemic stroke (AIS) who present within 3 to 4.5 hours of symptom onset and who meet the inclusion criteria for intravenous (IV) thrombolysis will receive, in a randomized, double-blind fashion, either IV Alteplase at 0.9 mg/kg per standard protocol or IV Tenecteplase at 0.25 mg/kg with saline infusion over one hour. Patients must also have no exclusion criteria for IV thrombolysis within the 3 to 4.5 hour window. The only required imaging is non-contrasted CT of the head. Patients will be monitored according to standard post-thrombolytic care. A CT of the head will be performed at 24 hours based on standard protocol or if there is any neurological change. Neurological function at 24 hours using NIHSS and at 3 months based on modified mRS and the NIHSS.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Phase IIb Study Comparing Tenecteplase to Alteplase in Acute Ischemic Stroke Within 3 to 4.5 Hours From Symptom Onset

Study Start Date :

Jan 1, 2015

Anticipated Primary Completion Date :

Jun 1, 2020

Anticipated Study Completion Date :

Jun 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tenecteplase Tenecteplase 0.25 mg/kg IV - Maximum dose: 25 mg	Drug: Tenecteplase Tenecteplase 0.25 mg/kg IV - Maximum 25 mg Other Names: TNKase
Active Comparator: Alteplase Alteplase 0.9 mg/kg IV - Maximum dose: 90 mg	Drug: Alteplase Alteplase 0.9 mg/kg IV - Maximum: 90 mg Other Names: Activase t-PA

Arm

Intervention/Treatment

Experimental: Tenecteplase

Tenecteplase 0.25 mg/kg IV - Maximum dose: 25 mg

Drug: Tenecteplase

Tenecteplase 0.25 mg/kg IV - Maximum 25 mg

Other Names:

TNKase

Active Comparator: Alteplase

Alteplase 0.9 mg/kg IV - Maximum dose: 90 mg

Drug: Alteplase

Alteplase 0.9 mg/kg IV - Maximum: 90 mg

Other Names:

Activase

t-PA

Outcome Measures

Primary Outcome Measures

Neurological outcome [90 days]
Measured by modified Rankin Scale score

Secondary Outcome Measures

Symptomatic intracranial hemorrhage [24 hours]
Twenty-four hour brain CT scan showing intracranial hemorrhage in conjuction with neurological deterioration of 4 points or more on the NIHSS

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 to 80 years
Acute neurologic deficit with an NIHSS ≥ 4
Non-enhanced computed tomography (NECT) of the head showing no hemorrhage
Acute ischemic stroke symptoms with onset, or time last known well, clearly defined between 3 and 4.5 hours
Treatment can be initiated within 3 to 4.5 hours from symptom onset

Exclusion Criteria:

Evidence of intracranial hemorrhage on NECT
Clinical suspicion of subarachnoid hemorrhage even with normal NECT
NECT shows hypo-density greater than 1/3 cerebral hemisphere)
History of intracranial hemorrhage/stroke
Uncontrolled HTN: At time treatment begins SBP remains >185 mmHg or DBP remains >110 mmHg despite repeated measurements
Known arteriovenous malformation, neoplasm, or aneurysm
Witnessed seizure at stroke onset
Acute bleeding tendencies
Platelet count <100,000/mm3
Heparin received in prior 48 hours with elevated aPTT
Current use of an anticoagulant (Coumadin/Warfarin) irrespective of INR
Prior use (within 48 hours) of direct thrombin inhibitors (dabigatran) or direct factor Xa inhibitors (rivaroxaban, apixaban)
Within prior 3 months: intracranial or spinal surgery, head trauma, or previous stroke
Arterial puncture at non-compressible site within last 7 days
Woman of child bearing age who has a positive pregnancy test
NIH stroke scale >25 (severe deficit) or <4 and no dysphasia (mild deficit) or rapidly improving
Symptoms spontaneously clearing
14 days post-operative or post major trauma
Recent gastrointestinal or urinary tract hemorrhage within the past 21 days
Recent acute MI within the past 3 months
Serum glucose <50 mg/dl or >400 mg/dL
Age >80 or less than 18
History of ischemic stroke AND diabetes mellitus
Unable to obtain consent from patient or power of attorney
Baseline mRS > 2
Consent not obtained by 20 minutes prior to closure of the therapeutic window.
The subject has been treated with a thrombolytic agent within the past 72 hours
The subject is a pregnant woman (positive serum βHCG pregnancy test, positive urine pregnancy test or clinically evident pregnancy)
The subject is, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any other reason