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

NCT05199662 | Recruiting Phase 3 DMC

• 1 other identifier: RESILIENT EXTEND-IV
• Study Type: interventional
• Target: 466
• Locations: 1 country
• Sites: 15

Brief 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. 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.

Conditions

Ischemic Stroke, Acute

Keywords

Ischemic Stroke; Thrombolysis; Tenecteplase

Outcome Measures

Primary Outcomes (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

  90 days

Secondary Outcomes (12)

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

  90 days

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

  90 days

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

  90 days

• 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)

  3-5 days

• 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)

  24 hours (-2/+12 hours)

Other Outcomes (1)

• Cost effectiveness analysis of IV TNK vs standard medical therapy

  12 months

Study Arms (2)

Control group

PLACEBO COMPARATOR

Placebo administered as a single bolus injection over 5 seconds

Drug: Placebo

Intravenous tenecteplase (TNK)

EXPERIMENTAL

Intravenous thrombolysis with Tenecteplase (TNK) at a dose of 0.25 mg/Kg (maximum 25mg, administered as a bolus over 5 seconds)

Drug: Intravenous tenecteplase

Interventions

Intravenous tenecteplase DRUG

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

Also known as: TNK, Metalyse

Intravenous tenecteplase (TNK)

Placebo DRUG

Placebo matching IV TNK

Control group

Eligibility Criteria

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

You may qualify if:

• 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:
• 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:

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Hospital Moinhos de Vento: lead
• Ministry of Health, Brazil: collaborator
• Boehringer Ingelheim: collaborator
• Brainomix Limited: collaborator
• iSchemaView, Inc: collaborator

Study Sites (15)

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90035000, Brazil

RECRUITING

Hospital das Clínicas Botucatu

Botucatu, Brazil

RECRUITING

Hospital das Clínicas - UNICAMP

Campinas, Brazil

RECRUITING

Hospital Universitário Maria Aparecida Pedrossian

Campo Grande, Brazil

RECRUITING

Hospital das Clínicas UFPR

Curitiba, Brazil

RECRUITING

Hospital Geral de Fortaleza

Fortaleza, 60175-295, Brazil

RECRUITING

Clinica Neurologica e Neurocirurgica de Joinville

Joinville, Brazil

RECRUITING

Hospital Metropolitano de Maceió

Maceió, Brazil

RECRUITING

Hospital de Clínicas de Porto Alegre

Porto Alegre, 90035-007, Brazil

RECRUITING

Hospital de Clínicas de Porto Alegre

Porto Alegre, Brazil

RECRUITING

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

Ribeirão Preto, 14015-010, Brazil

RECRUITING

Hospital de Base São José do Rio Preto

São José do Rio Preto, Brazil

RECRUITING

Hospital São Paulo

São Paulo, 04037-002, Brazil

RECRUITING

Santa Casa de Misericordia de Sao Paulo

São Paulo, Brazil

RECRUITING

Hospital Estadual Central

Vitória, Brazil

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; 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

Study Officials

• Gisele Sampaio Silva, MD, MPH, PhD

  Universidade Federal de São Paulo

  PRINCIPAL INVESTIGATOR

• Raul G Nogueira, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Sheila CO Martins, MD, PhD

  Hospital Moinhos de Vento

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gisele Sampaio Silva, MD, MPH, PhD

CONTACT

5511983580583; giselesampaio@hotmail.com

Leonardo Carbonera, MD, MsC

CONTACT

555135378195; leonardo.carbonera@hmv.org.br

Study Design

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

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: January 20, 2022
• Study Start: January 20, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 4, 2025

Record last verified: 2025-04

Locations

BR (15)