Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke
Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke
The proposed trial is a pragmatic, registry based, prospective, randomized (1:1) controlled,
 open-label parallel group clinical trial with blinded endpoint assessment of 1600 patients to
 test if intravenous tenecteplase (0.25 mg/kg body weight, max dose 25 mg) is non-inferior to
 intravenous alteplase (0.9 mg/kg body weight) in patients with acute ischemic stroke
 otherwise eligible for intravenous thrombolysis as per standard care. All patients will have
 standard of care medical management on an acute stroke unit. There are no additional trial
 specific management recommendations. Patients will be followed for approximately 90-120 days.
There are two established therapies for acute ischemic stroke, namely intravenous alteplase
 and endovascular thrombectomy (EVT). The guiding principles behind these therapies are fast,
 effective and safe reperfusion of ischemic brain. Patients with acute ischemic stroke
 presenting within 4.5 hours from symptom onset are administered intravenous alteplase. If
 there is evidence of large vessel occlusion (LVO), these patients are transferred to the
 nearest comprehensive stroke center (CSC) for EVT.Physicians, hospitals and health systems
 are focused on implementing efficient triaging systems and workflow processes to improve
 speed and efficacy of administration of these life-saving therapies. Although efforts over
 the years with intravenous alteplase administration has resulted in improvement in efficiency
 metrics like door to needle time (DTN) and door-in-door-out (DIDO) time, these metrics are
 still not optimal, and the therapy is underutilized. Physicians continue to have concerns
 about low early reperfusion rates, increased risk of symptomatic intracerebral hemorrhage and
 challenges with drug administration (bolus + 60-minute infusion) with intravenous alteplase.

 Recent phase II trials have shown that intravenous tenecteplase is potentially safer and may
 achieve higher early reperfusion rates than alteplase in patients with acute ischemic stroke.
 Bolus administration makes tenecteplase easier to administer than alteplase (which requires
 infusion pumps). Transfer of patients from primary stroke centers (PSC) to comprehensive
 stroke centers (CSCs) is potentially easier without infusion pumps. Moreover, depending on
 the province, tenecteplase either costs the same, or even less, than alteplase. It is
 therefore possible that the use of intravenous tenecteplase in patients with acute ischemic
 stroke otherwise eligible for intravenous alteplase may result in faster administration of
 thrombolysis and more efficient transport to CSCs, thus saving time, reducing adverse events
 (intracranial hemorrhage) and potentially improving patient outcomes, while saving the health
 system costs. For these various reasons, robust evidence that tenecteplase is non-inferior to
 alteplase as an intravenous thrombolytic agent in patients with acute ischemic stroke will
 change current clinical practice as it did in patients with myocardial infarction. The
 proposed trial is therefore a pragmatic, registry embedded, prospective, randomized (1:1)
 controlled, open-label parallel group clinical trial with blinded endpoint assessment of 1600
 patients to generate real world evidence whether intravenous tenecteplase (0.25 mg/kg body
 weight, max dose 25 mg) is non-inferior to intravenous alteplase (0.9 mg/kg body weight) in
 patients with acute ischemic stroke otherwise eligible for intravenous thrombolysis as per
 current standard of care.
Inclusion Criteria: Inclusion criteria is pragmatic.

 -  All patients with acute ischemic stroke eligible to receive intravenous alteplase as
 per standard care will be eligible for enrolment in the proposed trial.

 -  Patients eligible for endovascular thrombectomy in addition to intravenous
 thrombolysis are eligible for enrolment.

 Exclusion Criteria:

 -  Contra-indications to intravenous thrombolysis as used by treating physicians as
 current standard of care apply.

 -  The benefits of thrombolysis with intravenous alteplase in the pediatric population is
 unknown. Any patient < 18 years of age may therefore not be enrolled.

 -  Women with pregnancy known to the investigator by history or examination, without
 requiring pregnancy testing, may only be enrolled in consultation with an expert
 stroke physician (either in person or through tele-stroke)