A Randomised Trial of Tenecteplase vs. Alteplase in Acute Ischemic Stroke
Overview
- Phase
- Phase 3
- Intervention
- Tenecteplase
- Conditions
- Stroke, Acute
- Sponsor
- Haukeland University Hospital
- Enrollment
- 201
- Locations
- 1
- Primary Endpoint
- Proportion of patients with favorable functional outcome
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
Background: Alteplase is the only approved acute drug treatment in ischemic stroke and aims at dissolving arterial clots causing cerebral ischemia. The overall benefit of alteplase is substantial. However, there is considerable room for improvement as 2/3 of patients with large clots may not achieve reopening of the vessel and up to 40% of the patients remain severely disabled or die.
Tenecteplase, a modified tissue plasminogen activator, has been shown to be a more efficient and safer thrombolytic drug than alteplase in pre-clinical studies. Tenecteplase has replaced alteplase as thrombolytic treatment in myocardial infarction and may also be the drug of choice in ischemic stroke.
Tenecteplase and alteplase had a similar safety profile in the NOR-TEST trial and there were no differences in efficacy between the two treatment groups. However, a majority of patients had mild stroke which may be associated with a natural favorable prognosis.
In spite of these neutral results, tenecteplase has the potential to replace alteplase as the drug of choice, based on a better pharmacological profile and a simpler practical administration. There is, however, need for a higher number of patients to prove the efficacy and safety of tenecteplase.
Hypothesis: Tenecteplase 0.4 mg/kg is non-inferior compared with alteplase 0.9 mg/kg.
Detailed Description
Objectives: To compare efficacy and safety of tenecteplase 0.4 mg/kg (single bolus) vs. alteplase 0.9 mg/kg (10% bolus + 90% infusion/60 minutes) a) within 4½ hours after symptom onset; b) within 4½ hours after awakening with stroke symptoms, and c) as bridging therapy within 4½ hours before thrombectomy. Study design: NOR-TEST-2 is a multi-centre PROBE (prospective randomised, open-label, blinded endpoint) trial, designed to establish non-inferiority of tenecteplase as compared with alteplase for consecutively admitted patients with acute ischaemic stroke treated within 4½ hours after symptom onset. Randomisation tenecteplase:alteplase is 1:1. Endpoints: Primary endpoint is functional outcome (mRS 0-1) at 90 days (efficacy). Secondary endpoints include rates of cerebral hemorrhages on CT/MR at 24-48 hours and mortality (safety). Patient recruitment: All patients admitted to hospital with acute ischaemic stroke eligible for standard iv thrombolysis with alteplase and with pre-stroke mRS\<3 and NIHSS score of \>5 on admission are potentially eligible for NOR-TEST-2. Based on power calculations from NOR-TEST, NOR-TEST 2 aims at including 1036 patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Tenecteplase
Tenecteplase
Intervention: Tenecteplase
Alteplase
Alteplase
Intervention: Alteplase
Outcomes
Primary Outcomes
Proportion of patients with favorable functional outcome
Time Frame: 90 days
Modified Rankin Scale 0-1 (favorable= 0-1, unfavorable 2-6)
Secondary Outcomes
- Major neurological improvement(24 hours)
- Functional handicap(90 days)
- Symptomatic cerebral hemorrhage(24-48 hours)
- Any cerebral haemorrhage(24-48 hours)
- Mortality(90 days)