Study of Tenecteplase Versus Alteplase for Thrombolysis (Clot Dissolving) in Acute Ischemic Stroke

NCT ID: NCT01949948

Last Updated: 2017-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1050 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2016-12-31

Brief Summary

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).

Detailed Description

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.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tenecteplase

0.4 mg/kg single bolus intravenously

Group Type: ACTIVE_COMPARATOR

Tenecteplase

Intervention Type: DRUG

0.4 mg/kg single bolus intravenously

Alteplase

0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously

Group Type: ACTIVE_COMPARATOR

Alteplase

Intervention Type: DRUG

0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously

Interventions

Tenecteplase

0.4 mg/kg single bolus intravenously

Intervention Type: DRUG

Alteplase

0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously

Intervention Type: DRUG

Other Intervention Names

Metalyse; Actilyse

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Research Council of Norway

OTHER

Sponsor Role: collaborator

Lars Thomassen

OTHER

Sponsor Role: lead

Responsible Party

Lars Thomassen

Senior Consultant neurologist; Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Lars Thomassen, MD PhD Prof.

Role: STUDY_CHAIR

Dept. Neurology, Haukeland University HospitalBergen, Norway

Ulrike Waje-Andreassen, MD PhD Prof.

Role: STUDY_DIRECTOR

Dept. Neurology, Haukeland University Hospital, Bergen

Nicola Logallo, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Dept. Neurology, Haukeland University Hospital, Bergen, Norway

Locations

Haukeland University Hospital

Bergen, , Norway

Nordland Hospital

Bodø, , Norway

Drammen Hospital

Drammen, , Norway

Førde Central Hospital

Førde, , Norway

Haugesund Hospital

Haugesund, , Norway

Molde Hospital

Molde, , Norway

Akershus University Hospital

Nordbyhagen, , Norway

Ullevål University Hospital

Oslo, , Norway

Baerum Hospital

Rud, , Norway

Telemark Hospital

Skien, , Norway

Stavanger University Hosital

Stavanger, , Norway

St. Olav Hospital NTNU

Trondheim, , Norway

Tønsberg Hospital

Tønsberg, , Norway

Countries

Norway

References

Logallo N, Kvistad CE, Nacu A, Naess H, Waje-Andreassen U, Asmuss J, Aamodt AH, Lund C, Kurz MW, Ronning OM, Salvesen R, Idicula TT, Thomassen L. The Norwegian tenecteplase stroke trial (NOR-TEST): randomised controlled trial of tenecteplase vs. alteplase in acute ischaemic stroke. BMC Neurol. 2014 May 15;14:106. doi: 10.1186/1471-2377-14-106.

Reference Type: BACKGROUND

PMID: 24886064 (View on PubMed)

Novotny V, Kvistad CE, Naess H, Logallo N, Fromm A, Khanevski AN, Thomassen L. Tenecteplase, 0.4 mg/kg, in Moderate and Severe Acute Ischemic Stroke: A Pooled Analysis of NOR-TEST and NOR-TEST 2A. J Am Heart Assoc. 2023 Oct 17;12(20):e030320. doi: 10.1161/JAHA.123.030320. Epub 2023 Oct 13.

Reference Type: DERIVED

PMID: 37830342 (View on PubMed)

Ihle-Hansen H, Sandset EC, Ihle-Hansen H, Hagberg G, Thommessen B, Ronning OM, Kvistad CE, Novotny V, Naess H, Waje-Andreassen U, Thomassen L, Logallo N. Sex differences in the Norwegian Tenecteplase Trial (NOR-TEST). Eur J Neurol. 2022 Feb;29(2):609-614. doi: 10.1111/ene.15126. Epub 2021 Oct 4.

Reference Type: DERIVED

PMID: 34564893 (View on PubMed)

Thommessen B, Naess H, Logallo N, Kvistad CE, Waje-Andreassen U, Ihle-Hansen H, Ihle-Hansen H, Thomassen L, Morten Ronning O. Tenecteplase versus alteplase after acute ischemic stroke at high age. Int J Stroke. 2021 Apr;16(3):295-299. doi: 10.1177/1747493020938306. Epub 2020 Jul 6.

Reference Type: DERIVED

PMID: 32631157 (View on PubMed)

Ahmed HK, Logallo N, Thomassen L, Novotny V, Mathisen SM, Kurz MW. Clinical outcomes and safety profile of Tenecteplase in wake-up stroke. Acta Neurol Scand. 2020 Nov;142(5):475-479. doi: 10.1111/ane.13296. Epub 2020 Jun 23.

Reference Type: DERIVED

PMID: 32511749 (View on PubMed)

Kvistad CE, Novotny V, Kurz MW, Ronning OM, Thommessen B, Carlsson M, Waje-Andreassen U, Naess H, Thomassen L, Logallo N. Safety and Outcomes of Tenecteplase in Moderate and Severe Ischemic Stroke. Stroke. 2019 May;50(5):1279-1281. doi: 10.1161/STROKEAHA.119.025041.

Reference Type: DERIVED

PMID: 31009339 (View on PubMed)

Ronning OM, Logallo N, Thommessen B, Tobro H, Novotny V, Kvistad CE, Aamodt AH, Naess H, Waje-Andreassen U, Thomassen L. Tenecteplase Versus Alteplase Between 3 and 4.5 Hours in Low National Institutes of Health Stroke Scale. Stroke. 2019 Feb;50(2):498-500. doi: 10.1161/STROKEAHA.118.024223.

Reference Type: DERIVED

PMID: 30602354 (View on PubMed)

Logallo N, Novotny V, Assmus J, Kvistad CE, Alteheld L, Ronning OM, Thommessen B, Amthor KF, Ihle-Hansen H, Kurz M, Tobro H, Kaur K, Stankiewicz M, Carlsson M, Morsund A, Idicula T, Aamodt AH, Lund C, Naess H, Waje-Andreassen U, Thomassen L. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017 Oct;16(10):781-788. doi: 10.1016/S1474-4422(17)30253-3. Epub 2017 Aug 2.

Reference Type: DERIVED

PMID: 28780236 (View on PubMed)

Logallo N, Kvistad CE, Thomassen L. Therapeutic Potential of Tenecteplase in the Management of Acute Ischemic Stroke. CNS Drugs. 2015;29(10):811-8. doi: 10.1007/s40263-015-0280-9.

Reference Type: DERIVED

PMID: 26387127 (View on PubMed)

Other Identifiers

REK 2011/2435

Identifier Type: -

Identifier Source: org_study_id