The Norwegian Tenecteplase Stroke Trial 2

NCT03854500 | Terminated Phase 3 DMC

• 1 other identifier: 2018-003090-95
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke, Acute; Cerebrovascular Disorders; Ischemic Stroke

Keywords

Tenecteplase; Thrombolysis; Alteplase

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with favorable functional outcome

  Modified Rankin Scale 0-1 (favorable= 0-1, unfavorable 2-6)

  90 days

Secondary Outcomes (5)

• Symptomatic cerebral hemorrhage

  24-48 hours

• Any cerebral haemorrhage

  24-48 hours

• Major neurological improvement

  24 hours

• Functional handicap

  90 days

• Mortality

  90 days

Study Arms (2)

Tenecteplase

ACTIVE COMPARATOR

Tenecteplase

Drug: Tenecteplase

Alteplase

ACTIVE COMPARATOR

Alteplase

Drug: Alteplase

Interventions

Tenecteplase DRUG

0.4 mg/kg single bolus intravenously

Also known as: Metalyse

Tenecteplase

Alteplase DRUG

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

Also known as: Actilyse

Alteplase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Treatment \<4½ hours after stroke onset or after awakening with symptoms.
• Informed consent by patient or by patient's family
• Wake-Up Stroke: FLAIR-DWI mismatch on MRI as judged by the (neuro-) radiologist or neurologist.
• Thrombectomy: Occlusion of intracerebral artery technically accessible for endovascular embolectomy as defined by local treatment protocols.

You may not qualify if:

• Prestroke modified rankin scale of ≥3
• Large areas of hypodense ischaemic changes on baseline CT;
• Patients with systolic blood pressure \>185 mm Hg or diastolic blood pressure \>110 mm Hg in spite of acute antihypertensive treatment;
• Pregnant women (are treated with alteplase);
• Women with possible pregnancy (are treated with alteplase)
• Beast feeding women, if a 24 hours stop of feeding is not feasible.
• Clinical presentation suggesting subarachnoid haemorrhage even if baseline CT is normal;
• Known bleeding diathesis; use of oral anticoagulants with no antidot, INR ≥1,4; heparin \<48 hours and increased APTT; low molecular weight heparin(oid) \<24 hours; another investigational drug \<14 days;
• 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; CNS neurosurgery \<2 months; serious head trauma \<2 months; pericarditis; sepsis; any serious medical illness likely to interact with treatment; confounding pre-existent neurological or psychiatric disease; unlikely to complete follow-up;
• Any condition that, in the opinion of the investigator, puts a patient at risk if treated with thrombolysis.

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (1)

Haukeland University Hospital

Bergen, 5021, Norway

Location

Related Publications (3)

• 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.

  PMID: 28780236 BACKGROUND

• Kvistad CE, Naess H, Helleberg BH, Idicula T, Hagberg G, Nordby LM, Jenssen KN, Tobro H, Rorholt DM, Kaur K, Eltoft A, Evensen K, Haasz J, Singaravel G, Fromm A, Thomassen L. Tenecteplase versus alteplase for the management of acute ischaemic stroke in Norway (NOR-TEST 2, part A): a phase 3, randomised, open-label, blinded endpoint, non-inferiority trial. Lancet Neurol. 2022 Jun;21(6):511-519. doi: 10.1016/S1474-4422(22)00124-7. Epub 2022 May 4.

  PMID: 35525250 RESULT

• 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.

  PMID: 37830342 DERIVED

MeSH Terms

Conditions

Stroke; Cerebrovascular Disorders; Ischemic Stroke

Interventions

Tenecteplase; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, controlled multicenter study

Study Record Dates

• First Submitted: January 21, 2019
• First Posted: February 26, 2019
• Study Start: October 28, 2019
• Primary Completion: September 30, 2021
• Study Completion: December 31, 2021
• Last Updated: March 3, 2025

Record last verified: 2025-02

Locations

NO (1)