Study of Tenecteplase Versus Alteplase for Thrombolysis (Clot Dissolving) in Acute Ischemic Stroke (NOR-TEST)
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| ClinicalTrials.gov Identifier: NCT01949948 |
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Recruitment Status :
Completed
First Posted : September 25, 2013
Last Update Posted : May 9, 2017
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BACKGROUND: Alteplase dissolves blood vessel clots in acute ischemic stroke and is the only approved acute drug treatment <4½ hours of stroke onset. The overall benefit from alteplase is substantial, but up to 2/3 of patients with large artery clots may not achieve reopening of the vessel and up to 40% of the patients may remain severely disabled or die, leaving substantial room for improvement. Tenecteplase, widely used in coronary heart disease, may be more effective and may have less bleeding complications than alteplase, and may be the drug of choice also in stroke.
HYPOTHESIS: Tenecteplase may be given safely to patients with acute ischemic stroke at a dose that is associated with improved clinical outcome compared with existing treatment options.
AIMS: To compare efficacy and safety of tenecteplase vs. alteplase given <4½ hours after symptom onset.
STUDY ENDPOINTS: The primary study endpoint is excellent clinical outcome at 3 months (effect). Secondary study endpoints are major early clinical improvement (effect) and bleeding complications (safety).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ischemic Stroke | Drug: Tenecteplase Drug: Alteplase | Phase 3 |
HYPOTHESIS: 1) Tenecteplase 0.4 mg/kg may be given safely to patients with acute ischaemic stroke <4½ hours after stroke onset. 2) Tenecteplase 0,4 mg/kg (single bolus)has superior efficacy and safety compared with alteplase 0.9 mg/kg (10% bolus + 90% infusion/60 minutes) when given within 4 ½ hours after stroke onset.
DESIGN: NOR-TEST is a multi-centre PROBE (prospective randomised, open-label, blinded endpoint) trial with randomisation tenecteplase:alteplase 1:1.
POWER CALCULATION: NOR-TEST aims at detecting a 9 % higher percentage excellent outcome with tenecteplase vs. alteplase (r1=0.40; r2=0.49; OR 1.44; power 0.8), and will include 954 patients during 3 years.
PATIENT RECRUITMENT: All patients found eligible for thrombolytic therapy are eligible for NOR-TEST, i.e. NOR-TEST changes neither inclusion nor exclusion criteria. The number of patients treated at a participating centre will therefore essentially remain unchanged. Estimated 400 patients are thrombolysed per year in participating centres. Allowing for 20% of patients not being included in NOR-TEST, the total number of patients (n=954) will still be met.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1050 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Randomised Trial of Tenecteplase vs. Alteplase for Recanalisation in Acute Ischemic Stroke |
| Actual Study Start Date : | September 2012 |
| Actual Primary Completion Date : | December 31, 2016 |
| Actual Study Completion Date : | December 31, 2016 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Tenecteplase
0.4 mg/kg single bolus intravenously
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Drug: Tenecteplase
0.4 mg/kg single bolus intravenously
Other Name: Metalyse |
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Active Comparator: Alteplase
0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously
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Drug: Alteplase
0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously
Other Name: Actilyse |
- Clinical: Functional handicap [ Time Frame: 90 days ]Excellent outcome defined as mRS 0-1
- Symptomatic cerebral hemorrhage [ Time Frame: 24-36 hours ]Haemorrhagic transformation (haemorrhagic infarct / haematoma) as defined by CT (or MRI)
- Hemorrhagic transformation [ Time Frame: 24-36 hours ]Any hemorrhagic infarct or parenchymal hematoma
- Neurological improvement [ Time Frame: 24 hours ]NIHSS changes from baseline: NIHSS=0 or reduction of ≥4 NIHSS points
- Clinical: Functional handicap [ Time Frame: 90 days ]Ordinal shift analysis of mRS
- Safety [ Time Frame: 90 days ]Death
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age 18 years or older
- Ischaemic stroke with measurable deficit on NIH Stroke Scale
- All stroke sub-types, severities and vascular distributions,a visible arterial occlusion is not required for inclusion
- Treatment within 4 ½ hours of stroke onset
- Patients awakening with symptoms are defined by the time last observed normal and awake
- Informed written consent signed by the patient, verbal consent from the patients as witnessed by a non-participating health care person, or consent by the signature of the patient's family must be provided
Exclusion Criteria:
- Patients with premorbid modified Rankin Scale (mRS) score ≥3
- Patients for whom a complete NIH Stroke Score cannot be obtained
- Hemiplegic migraine with no arterial occlusion on CTA
- Seizure at stroke onset and no visible occlusion on baseline CTA
- Intracranial haemorrhage on baseline CT
- Clinical presentation suggesting subarachnoid haemorrhage even if baseline CT is normal
- Large areas of hypodense ischaemic changes on baseline CT
- Patients with systolic blood pressure >185 mm Hg or diastolic blood pressure >110 mm Hg
- Female, pregnant or breast feeding
- Known bleeding diathesis
- Use of oral anticoagulants and International Normalized Ratio (INR) ≥1,4
- Use of new oral anticoagulants (NOAC) within the last 12 hours
- Heparin <48 hours and increased Activated partial thromboplastin tike (APTT)
- Low molecular weight heparin(oid) <24 hours
- Any other investigational drug <14 days
- Sepsis
- Patients with arterial puncture at a noncompressible site or lumbar puncture <7 days
- Major surgery or serious trauma <14 days
- Gastrointestinal or urinary tract hemorrhage <14 days
- Clinical stroke <2 months
- History of intracranial haemorrhage
- Brain neurosurgery <2 months
- Serious head trauma <2 months
- Pericarditis
- Any serious medical illness likely to interact with treatment
- Confounding pre-existent neurological or psychiatric disease
- Unlikely to complete follow-up
- Pregnancy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01949948
| Norway | |
| Haukeland University Hospital | |
| Bergen, Norway, 5021 | |
| Nordland Hospital | |
| Bodø, Norway, 8092 | |
| Drammen Hospital | |
| Drammen, Norway, 3004 | |
| Førde Central Hospital | |
| Førde, Norway, 6800 | |
| Haugesund Hospital | |
| Haugesund, Norway, 5516 | |
| Molde Hospital | |
| Molde, Norway, 6400 | |
| Akershus University Hospital | |
| Nordbyhagen, Norway, 1474 | |
| Ullevål University Hospital | |
| Oslo, Norway, 0424 | |
| Baerum Hospital | |
| Rud, Norway, 1309 | |
| Telemark Hospital | |
| Skien, Norway, 3710 | |
| Stavanger University Hosital | |
| Stavanger, Norway, 4017 | |
| St. Olav Hospital NTNU | |
| Trondheim, Norway, 7006 | |
| Tønsberg Hospital | |
| Tønsberg, Norway, 3100 | |
| Study Chair: | Lars Thomassen, MD PhD Prof. | Dept. Neurology, Haukeland University HospitalBergen, Norway | |
| Study Director: | Ulrike Waje-Andreassen, MD PhD Prof. | Dept. Neurology, Haukeland University Hospital, Bergen | |
| Principal Investigator: | Nicola Logallo, MD PhD | Dept. Neurology, Haukeland University Hospital, Bergen, Norway |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Lars Thomassen, Senior Consultant neurologist; Professor, Haukeland University Hospital |
| ClinicalTrials.gov Identifier: | NCT01949948 |
| Other Study ID Numbers: |
REK 2011/2435 |
| First Posted: | September 25, 2013 Key Record Dates |
| Last Update Posted: | May 9, 2017 |
| Last Verified: | May 2017 |
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treatment, intervention, thrombolysis |
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Stroke Ischemic Stroke Cerebral Infarction Ischemia Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases |
Pathologic Processes Brain Infarction Brain Ischemia Infarction Necrosis Tissue Plasminogen Activator Tenecteplase Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action |