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The Norwegian Tenecteplase Stroke Trial 2 (NOR-TEST 2)

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ClinicalTrials.gov Identifier: NCT03854500
Recruitment Status : Not yet recruiting
First Posted : February 26, 2019
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
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 has superior efficacy and similar safety profile compared with alteplase 0.9 mg/kg.


Condition or disease Intervention/treatment Phase
Stroke, Acute Cerebrovascular Disorders Ischemic Stroke Drug: Tenecteplase Drug: Alteplase Phase 3

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 superiority of tenecteplaseas 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 1342 patients.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1342 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, controlled multicenter study
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Trial of Tenecteplase vs. Alteplase in Acute Ischemic Stroke
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : February 28, 2023
Estimated Study Completion Date : May 28, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Tenecteplase
Tenecteplase
Drug: Tenecteplase
0.4 mg/kg single bolus intravenously
Other Name: Metalyse

Active Comparator: Alteplase
Alteplase
Drug: Alteplase
0.9 mg/kg as 10% bolus + 90% infusion/60 minutes intravenously
Other Name: Actilyse




Primary Outcome Measures :
  1. Proportion of patients with favorable functional outcome [ Time Frame: 90 days ]
    Modified Rankin Scale 0-1 (favorable= 0-1, unfavorable 2-6)


Secondary Outcome Measures :
  1. Symptomatic cerebral hemorrhage [ Time Frame: 24-48 hours ]
    Proportion of patients with haemorrhagic infarct/haematoma as defined by CT or MRI

  2. Any cerebral haemorrhage [ Time Frame: 24-48 hours ]
    Proportion of patients haemorrhagic infarct/haematoma as defined by CT or MRI

  3. Major neurological improvement [ Time Frame: 24 hours ]
    Proportion of patients >3 Points improvement by NIHSS score or NIHSS score 0 (NIHSS score range is 0-42)

  4. Functional handicap [ Time Frame: 90 days ]
    Ordinal shift analysis of modified Rankin scale (0-6)

  5. Mortality [ Time Frame: 90 days ]
    Proportion of patients who died



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

General inclusion criteria

  • 18 years or older
  • Ischaemic stroke with clinical symptoms corresponding to National Institutes of Health Stroke Scale Score (NIHSS) of >5. All stroke sub-types and vascular distributions are eligible. A visible arterial occlusion is not required for inclusion.
  • Treatment <4½ hours after stroke onset or after awakening with symptoms.
  • Informed consent by patient or by patient`s family

Specific sub-set inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Information from the National Library of Medicine

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): NCT03854500


Contacts
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Contact: Christopher Elnan Kvistad, PhD 92422048 Echr@helse-bergen.no
Contact: Lars Thomassen, Prof, PhD ltho@helse-bergen.no

Sponsors and Collaborators
Haukeland University Hospital

Publications:
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Responsible Party: Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT03854500     History of Changes
Other Study ID Numbers: 2018-003090-95
First Posted: February 26, 2019    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Haukeland University Hospital:
Tenecteplase
Thrombolysis
Alteplase
Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Ischemia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Tissue Plasminogen Activator
Tenecteplase
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action