Clarification: The SURPASS Trial Does Not Exist in the Provided Evidence
I cannot find any reference to a "SURPASS trial" in the evidence provided. The evidence discusses various thrombolytic agents and trials (NINDS, PROACT-I/II, NOR-TEST, etc.), but no SURPASS trial is mentioned.
Current Standard of Care for Thrombolytic Therapy in Acute Ischemic Stroke
Intravenous recombinant tissue plasminogen activator (r-tPA/alteplase) at 0.9 mg/kg (maximum 90 mg) remains the only FDA-approved and guideline-recommended thrombolytic agent for acute ischemic stroke, with the strongest evidence supporting treatment within 3 hours of symptom onset. 1, 2
Time-Based Treatment Algorithm
Within 0-3 hours: Administer IV r-tPA 0.9 mg/kg (maximum 90 mg) - Grade 1A recommendation with 154 additional favorable outcomes per 1,000 patients treated 1, 2
- Give 10% as bolus over 1 minute, followed by 90% infused over 60 minutes 3
Within 3-4.5 hours: Consider IV r-tPA 0.9 mg/kg (maximum 90 mg) - Grade 2C recommendation with 69 additional favorable outcomes per 1,000 patients treated 1, 2
Beyond 4.5 hours: Do not administer IV r-tPA - Grade 1B recommendation against treatment 1
Alternative Thrombolytic Agents: Current Evidence
Tenecteplase (TNK) at 0.25 mg/kg shows promise as an alternative to alteplase but is not yet FDA-approved or guideline-recommended for routine use in acute ischemic stroke. 4, 5
Tenecteplase Evidence Summary:
Dose of 0.25 mg/kg: Meta-analysis suggests greatest odds of achieving 90-day excellent independence (mRS 0-1) compared to alteplase, with similar safety profile and no increased risk of symptomatic intracranial hemorrhage 4
Dose of 0.4 mg/kg: Associated with increased odds of symptomatic intracranial hemorrhage compared to alteplase - should be avoided 4
NOR-TEST trial (2017): The largest phase 3 trial comparing tenecteplase 0.4 mg/kg to alteplase in 1,100 patients found tenecteplase was not superior to alteplase (64% vs 63% achieved mRS 0-1, p=0.52), with similar safety profiles 6
Current status: Four phase III trials are ongoing or recently completed (NOR-TEST, TASTE, TEMPO-2, TALISMAN) to establish definitive evidence 7
Agents That Should NOT Be Used
Streptokinase is absolutely contraindicated in acute ischemic stroke due to unacceptably high hemorrhage rates. 1
- Other agents (urokinase, reteplase, anistreplase, staphylokinase) have not been tested extensively and lack evidence for use 1
Intraarterial Thrombolysis
For proximal cerebral artery occlusions in patients who do not meet IV r-tPA eligibility criteria: Consider intraarterial r-tPA within 6 hours of symptom onset - Grade 2C recommendation 1, 2
Recombinant pro-urokinase (r-pro-UK): Was studied in PROACT-I and II trials for intraarterial use but is not FDA-approved 1
Critical Safety Considerations
Symptomatic intracranial hemorrhage occurs in 4-6% of appropriately selected patients treated with alteplase 3
Blood pressure must be controlled below 185/110 mmHg prior to thrombolytic administration 3
Adjunctive aspirin 160-325 mg should be administered within 48 hours after stroke onset, but not simultaneously with thrombolytic therapy 1, 2
Common Pitfall
Do not delay IV r-tPA administration while waiting for tenecteplase or other investigational agents, as alteplase remains the evidence-based standard of care with proven mortality and morbidity benefits. 1, 2