The Norwegian Tenecteplase Stroke Trial 2
- Conditions
- Ischemic StrokeCerebrovascular DisordersStroke, Acute
- Interventions
- Registration Number
- NCT03854500
- Lead Sponsor
- Haukeland University Hospital
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 201
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Alteplase Alteplase Alteplase Tenecteplase Tenecteplase Tenecteplase
- Primary Outcome Measures
Name Time Method Proportion of patients with favorable functional outcome 90 days Modified Rankin Scale 0-1 (favorable= 0-1, unfavorable 2-6)
- Secondary Outcome Measures
Name Time Method Major neurological improvement 24 hours Proportion of patients \>3 Points improvement by NIHSS score or NIHSS score 0 (NIHSS score range is 0-42)
Functional handicap 90 days Ordinal shift analysis of modified Rankin scale (0-6)
Symptomatic cerebral hemorrhage 24-48 hours Proportion of patients with haemorrhagic infarct/haematoma as defined by CT or MRI
Any cerebral haemorrhage 24-48 hours Proportion of patients haemorrhagic infarct/haematoma as defined by CT or MRI
Mortality 90 days Proportion of patients who died
Trial Locations
- Locations (1)
Haukeland University Hospital
🇳🇴Bergen, Norway