The HOPE Trial and Tenecteplase for Acute Ischemic Stroke
I cannot find any evidence of a "HOPE trial" specifically examining tenecteplase or tissue plasminogen activator for acute ischemic stroke in the provided literature. The question appears to reference a trial that is not included in the available evidence base.
What the Evidence Actually Shows About Tenecteplase
The most robust recent evidence comes from the ORIGINAL trial (2024), which demonstrated that tenecteplase at 0.25 mg/kg was noninferior to alteplase for achieving excellent functional outcomes (mRS 0-1) at 90 days in patients treated within 4.5 hours of stroke onset. 1
Key Clinical Trials on Tenecteplase
The major trials examining tenecteplase versus alteplase include:
ORIGINAL Trial (2024): This multicenter Chinese trial of 1,465 patients showed tenecteplase 0.25 mg/kg achieved excellent outcomes (mRS 0-1) in 72.7% versus 70.3% with alteplase (RR 1.03,95% CI 0.97-1.09), meeting noninferiority criteria. 1 Symptomatic ICH rates were identical at 1.2% in both groups. 1
Australian Phase 2B Trial (2012): This smaller trial of 75 patients demonstrated that tenecteplase 0.25 mg/kg was superior to alteplase for reperfusion and clinical outcomes, with 72% achieving absence of serious disability at 90 days versus 40% with alteplase (P=0.02). 2
EXTEND-IA TNK Trial: Demonstrated higher reperfusion rates with tenecteplase (22% vs 10% substantial reperfusion) prior to mechanical thrombectomy, though it was not powered for clinical outcomes. 3
Current Guideline Recommendations
The American Heart Association/American Stroke Association states that tenecteplase might be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level of Evidence B-R). 3
Alteplase remains the FDA-approved standard, administered as 0.9 mg/kg (maximum 90 mg) with 10% as bolus and 90% over 60 minutes. 4, 3
Tenecteplase offers single-bolus weight-based administration: 30 mg for <60 kg, 35 mg for 60-69 kg, with dosing up to 0.25 mg/kg. 3
The benefit of IV fibrinolytic agents other than alteplase and tenecteplase is unproven and not recommended outside clinical trials. 3
Practical Advantages of Tenecteplase
The longer half-life of tenecteplase (90-130 minutes) permits single-bolus administration, offering significant workflow advantages over alteplase's 1-hour infusion, particularly in centers considering endovascular therapy or patient transfer. 3, 5
Single-bolus administration reduces nursing time and potential medication errors. 3
Mayo Clinic data (2024) showed tenecteplase was associated with lower symptomatic ICH rates (0.65% vs 5%, P=0.027) and higher spontaneous recanalization rates (10.4% vs 1.4%, P=0.038) compared to alteplase. 6
Critical Caveats
Both agents share identical contraindications including intracranial hemorrhage, recent significant trauma or surgery, and uncontrolled hypertension. 3
Streptokinase should never be used due to unacceptably high hemorrhage rates. 4, 3
Other agents (reteplase, urokinase, anistreplase) lack extensive testing and are not recommended. 4, 3
Careful patient selection remains critical regardless of which thrombolytic is chosen, particularly in patients on novel oral anticoagulants where reliable assays and clinical history are essential. 3