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Ischemic Stroke, AcutePhase 3EXTEND-IVNCT05199662

Randomization to Extend Stroke Intravenous ThromboLysis In Evolving Non-Large Vessel Occlusion With TNK (RESILIENT

A Phase 3 study testing Intravenous tenecteplase in people with Ischemic Stroke, Acute, run by Hospital Moinhos de Vento at 15 sites in Brazil.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

A phase III, randomized, multi-center clinical trial that will examine whether treatment with intravenous TNK is superior to placebo in patients who suffer a non-large vessel occlusion ischemic stroke within 4.5-12 hours from time last seen well. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ischemic Stroke, Acute
What is being tested?
Intravenous tenecteplase
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
466 participants
Where
15 sitesBrazil
Study dates
20 Jan 2022to Jul 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Acute ischemic stroke where patient is ineligible for IV thrombolytic treatment with Alteplase due to onset >4.5 hours and is ineligible for endovascular treatment under standard of care due to absence of proximal arterial occlusion (e.g. intracranial ICA, MCA-M1 and dominant M2 segments, and vertebrobasilar arteries).
  • Dominant M2 segment is defined is a division supplying >50% of the MCA territory vs co-dominant supplying 50% of the MCA territory vs non-dominant supplying <50% of the MCA territory.
  • No significant pre-stroke functional disability (mRS ≤2).
  • Age ≥18 years (no upper age limit).
  • Clinical or imaging mismatch evidence in distal artery territories, defined as one of the following scenarios (A, B or C):
  • Scenario A - all of the following:
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  • Significant cortical neurological deficit (moderate to severe afasia, moderate to severe heminegligence, severe hemianopsia) with the addition or not of motor symptoms OR any motor deficit accompanied of cortical symptoms of any severity;
  • Contrast-enhanced CT of the head or head MRI with <50% involvement of the vascular territory corresponding to the clinical manifestation;
  • Arterial head angiotomography or arterial head angioMRI WITHOUT proximal intracranial artery occlusion that would require endovascular therapy (for example, ICA intracranial, MCA-M1 and M2 dominant segments and vertebral and basilar arteries)
  • Scenario B - all of the following:
  • NIHSS score ≥ 4 due to any neurologic deficits;
  • Non-contrast CT of the head or head MRI com <50% involvement of the vascular territory corresponding to the clinical manifestation;
  • Arterial head angioCT or arterial head MRI WITHOUT proximal intracranial artery occlusion that would require endovascular therapy (for example, ICA intracranial, MCA-M1 and M2 dominant segments and vertebral and basilar arteries)
  • Arterial head angioCT with distal occlusion on MIP or wedge-shaped lesion on parenchymography on the source-image of angiotomography OR CT perfusion with wedge-shaped cortical lesion.
  • Scenario C - all of the following:
  • NIHSS score ≥ 4 due to any neurologic deficits;
  • The presence of a Target Mismatch defined as:
  • Ischemic Core <50cc (defined on NCCT/CTP* or DWI MRI) *Volume NCCT can be used to exclude patients if the investigator believes that its volume assessment is more reliable that the CTP in any particular case.
  • Mismatch Volume (Tmax >6sec lesion - Core volume lesion) >10cc
  • Mismatch Ratio >1.4
  • Patient treatable within 4.5-12 hours of symptom onset. Symptoms onset is defined as point in time the patient was last seen well (at baseline). Treatment start is defined as initiation of IV TNK or placebo infusion.
  • Patients who have woken up with the symptoms and don't have a mismatch FLAIR-DWI according to the WAKE-UP Trial image criteria will have their window considered to be >4.5 hours. In this case, the time last seen well must have been 12 hours at most.
  • Informed consent obtained from patient or acceptable patient surrogate.

Who cannot join

  • Intracranial hemorrhage (ICH) identified by CT or MRI.
  • Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in the patient without eligibility criteria.
  • Pre-stroke mRS score of ≥ 2 (indicating previous disability)
  • Contra indication to imaging with MR or CT with contrast agents.
  • Infarct core >1/3 MCA territory qualitatively or >50 mL quantitatively (determined by DWI lesion on MR).
  • Participation in any investigational study in the previous 30 days
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  • Any terminal illness such that patient would not be expected to survive more than 1 year).
  • Baseline platelet count < 100.000/µL
  • Woman of childbearing potential who is known to be pregnant or who has a positive pregnancy test on admission.
  • Previous stroke within last three months.
  • Recent past history or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm other than meningioma.
  • Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1.6).
  • Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged partial thromboplastin time exceeding the upper limit of the local laboratory normal range
  • Use of glycoprotein IIb - IIIa inhibitors within the past 72 hours. Use of single agent oral platelet inhibitors (clopidogrel or low-dose aspirin) prior to study entry is permitted.
  • Clinically significant hypoglycemia.
  • Uncontrolled hypertension defined by a blood pressure > 185 mmHg systolic or >110 mmHg diastolic on at least 2 separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure to within these limits. The definition of "aggressive treatment" is left to the discretion of the responsible Investigator.
  • Hereditary or acquired hemorrhagic diathesis.
  • Gastrointestinal or urinary bleeding within the preceding 21 days.
  • Major surgery within the preceding 14 days which poses risk in the opinion of the Investigator.
  • Exposure to a thrombolytic agent within the previous 72 hours.
  • Subject participating in a study involving an investigational drug or device that would impact this study.

Trial locations and contacts

15 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Gisele Sampaio Silva, MD, MPH, PhD contact

5511983580583

giselesampaio@hotmail.com

Leonardo Carbonera, MD, MsC contact

555135378195

leonardo.carbonera@hmv.org.br

15 sites in 1 country

Brazil15 sites, 15 recruiting

  • Hospital das Clínicas Botucatu

    Botucatu

    Rodrigo Bazan, MD

    Recruiting

  • Hospital das Clínicas - UNICAMP

    Campinas

    Wagner Avelar, MD

    Recruiting

  • Hospital Universitário Maria Aparecida Pedrossian

    Campo Grande

    Gabriel Braga

    Recruiting

  • Hospital das Clínicas UFPR

    Curitiba

    Viviane Zetola, MD

    Recruiting

  • Hospital Geral de Fortaleza

    Fortaleza, 60175-295

    Fabricio Lima, MD, PhD

    Recruiting

  • Clinica Neurologica e Neurocirurgica de Joinville

    Joinville

    Carla Moro

    Recruiting

  • Hospital Metropolitano de Maceió

    Maceió

    Rebeca Teixeira, MD

    Recruiting

  • Hospital Moinhos de Vento

    Porto Alegre, Rio Grande do Sul, 90035000

    Sheila Martins

    Recruiting

  • Hospital de Clínicas de Porto Alegre

    Porto Alegre, 90035-007

    Andrea Almeida

    Recruiting

  • Hospital de Clínicas de Porto Alegre

    Porto Alegre

    Andrea Almeida, MD

    Recruiting

  • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo

    Ribeirão Preto, 14015-010

    Octavio Marques Pontes-Neto, MD, PhD

    Recruiting

  • Hospital de Base São José do Rio Preto

    São José do Rio Preto

    Mariana Battaglini, MD

    Recruiting

  • Hospital São Paulo

    São Paulo, 04037-002

    Gisele Sampaio Silva, MD, PhD

    Maramelia Miranda Alves, MD, MsC

    Recruiting

  • Santa Casa de Misericordia de Sao Paulo

    São Paulo

    Rubens Gagliardi

    Recruiting

  • Hospital Estadual Central

    Vitória

    José Fiorot JR, MD

    Recruiting

Other trials in Brazil

About this study

Official title: A Phase III, Randomized, Multi-center Clinical Trial That Will Examine Whether Treatment With Intravenous TNK is Superior to Placebo in Patients Who Suffer a Non-large Vessel Occlusion Ischemic Stroke Within 4.5-12 Hours From Time Last Seen Well

A phase III, randomized, multi-center clinical trial that will examine whether treatment with intravenous TNK is superior to placebo in patients who suffer a non-large vessel occlusion ischemic stroke within 4.5-12 hours from time last seen well. The randomization employs a 1:1 ratio of intravenous thrombolysis with Tenecteplase (TNK) versus placebo in patients who suffer a non-large vessel occlusion ischemic stroke between 4.5 and 12 hours from time last seen well (TLSW) and with a clinical-radiological mismatch or evidence of salvageable brain tissue on perfusion imaging.

Read the detailed description

Prospective, multi-center, randomized, controlled, double blinded trial. The randomization employs a 1:1 ratio of intravenous thrombolysis with Tenecteplase (TNK) versus placebo in patients who suffer a non-large vessel occlusion ischemic stroke between 4.5 and 12 hours from time last seen well (TLSW) and with a clinical-radiological mismatch or evidence of salvageable brain tissue on perfusion imaging. Randomization will be done under a minimization process using age (≤70 vs. >70 years), baseline NIHSS (≤10 vs. >10), therapeutic window (4.5-9 or 9-12 hours after TLKW), randomization scenario and clinical site. For the primary endpoint, subjects will be followed for 90 days post-randomization.

The total sample size is 466 participants (233 in each arm). Interim analysis is planned with 40% and 67% of the total sample, with the possibility of stopping due to efficacy or futility, in addition to an adaptive design based on the conditional probability of a positive result.

Being tested
Intravenous tenecteplase, Placebo
Keywords
Ischemic Stroke, Thrombolysis, Tenecteplase
Medical subject headings
Ischemic Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intravenous tenecteplaseDrug

    Also called TNK, Metalyse

    Intravenous tenecteplase (TNK). Patients will receive intravenous TNK (0.25mg/kg, maximum 25mg, administered as a bolus over 5 seconds).

  • PlaceboDrug

    Placebo matching IV TNK

Study groups in NCT05199662
Study groupRoleWhat they receive
Control groupPlacebo comparatorPlacebo administered as a single bolus injection over 5 seconds
Receives: Drug: Placebo
Intravenous tenecteplase (TNK)ExperimentalIntravenous thrombolysis with Tenecteplase (TNK) at a dose of 0.25 mg/Kg (maximum 25mg, administered as a bolus over 5 seconds)
Receives: Drug: Intravenous tenecteplase

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rates of Good Functional Outcomes adjusted for the baseline mRS and stroke severity (NIHSS) according to the modified Rankin Scale scores at 90 days

    Rates of Good Functional Outcomes adjusted for the baseline mRS and stroke severity (NIHSS) according to the modified Rankin Scale scores at 90 days as following:

    Baseline mRS=0 and NIHSS <10: mRs 90 days ≤1 Baseline mRS=1 and NIHSS ≥10: mRs 90 days ≤2

    Measured: 90 days

Secondary outcomes (12)

  1. Rates of Excellent Outcome defined as mRS ≤ 1 and/ or equal to Baseline mRS at 90 days

    Rates of Excellent Outcome defined as mRS ≤ 1 and/ or equal to Baseline mRS at 90 days

    Measured: 90 days

  2. Rates of Independent Outcome defined as mRS ≤ 2 and/ or equal to Baseline mRS at 90 days

    Rates of Independent Outcome defined as mRS ≤ 2 and/ or equal to Baseline mRS at 90 days

    Measured: 90 days

  3. Mean score for disability on the utility-weighted modified Rankin scale (UW-mRS) at 90 days

    Mean score for disability on the utility-weighted modified Rankin scale (UW-mRS) at 90 days

    Measured: 90 days

  4. Final infarct volume (FIV) and infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 3-5 days (if available)

    Final infarct volume (FIV) and infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 3-5 days (if available)

    Measured: 3-5 days

  5. Final infarct volume (FIV) and infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 24 hours (-2/+12 hours)

    Final infarct volume (FIV) and infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 24 hours (-2/+12 hours)

    Measured: 24 hours (-2/+12 hours)

  6. Dramatic early favorable response as determined by an NIHSS of 0-2 or NIHSS improvement ≥ 4 points at 24 (-2/+12 hours) hours

    Dramatic early favorable response as determined by an NIHSS of 0-2 or NIHSS improvement ≥ 4 points at 24 (-2/+12 hours) hours

    Measured: 24 (-2/+12 hours) hours

  7. Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year, between interventional therapy vs medical therapy alone

    Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year, between interventional therapy vs medical therapy alone

    Measured: 3 month, 6 months and one year

  8. Brain tissue reperfusion evaluated by CT or MRI perfusion at 24 hours in both treatment groups (if available)

    Brain tissue reperfusion evaluated by CT or MRI perfusion at 24 hours in both treatment groups (if available)

    Measured: 24 hours

  9. Mortality at 90 days ( safety outcome)

    Mortality at 90 days ( safety outcome)

    Measured: 90 days

  10. Clinically significant ICH rates at 24 (-2/+12) hours.

    Clinically significant ICH rates at 24 (-2/+12) hours. All intracerebral hemorrhages will be classified by a central core-lab using the ECASS criteria. Symptomatic ICH will be defined as per the modified SITS-MOST definition: local or remote parenchymal hemorrhage type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage on the post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 h, or leading to death that the CEC/DSMB judges is causative of the deterioration.

    Measured: 24 (-2/+12) hours

  11. Incidence of any intracranial hemorrhage (Heidelberg criteria) measured at 24 (-2/+12)

    Incidence of any intracranial hemorrhage (Heidelberg criteria) measured at 24 (-2/+12) hours

    Measured: 24 (-2/+12)

  12. Distribution of the modified Rankin Scale scores at 90 days (shift analysis) as evaluated by two separate assessors at the central core lab) who are blinded to treatment.

    Distribution of the modified Rankin Scale scores at 90 days (shift analysis) as evaluated by two separate assessors at the central core lab) who are blinded to treatment. Primary Endpoint will consider central core lab readings only (video interview with RFA method) with local reading as a back-up mechanism

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2022
  2. Study start20 Jan 2022
  3. Primary completionJul 2026 (estimated)
  4. Study completionJul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
466 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05199662
Sponsor's protocol ID
RESILIENT EXTEND-IV
Acronym
EXTEND-IV
Status last verified
Apr 2025
First submitted
13 Dec 2021
Last updated
4 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Intravenous tenecteplase in people with Ischemic Stroke, Acute, run by Hospital Moinhos de Vento at 15 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Gisele Sampaio Silva, MD, MPH, PhD (5511983580583, giselesampaio@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rates of Good Functional Outcomes adjusted for the baseline mRS and stroke severity (NIHSS) according to the modified Rankin Scale scores at 90 days (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05199662.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2025; AzTrials last refreshed its copy on 29 Oct 2026.

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