Randomization to Endovascular Treatment Alone or Preceded by Systemic Thrombolysis With Tenecteplase in Ischemic Stroke

NCT05199194 | Recruiting Phase 3 DMC

• 1 other identifier: RESILIENT DIRECT-TNK
• Study Type: interventional
• Target: 398
• Locations: 1 country
• Sites: 13

Brief Summary

A phase III randomized, multi-center, double-blinded, placebo-controlled clinical trial that will examine two strategies for the treatment of acute ischemic stroke associated with a large vessel anterior occlusion within 4.5 hours from symptoms onset: direct endovascular treatment vs. endovascular treatment preceded by intravenous tenecteplase.

Conditions

Stroke, Ischemic; Stroke, Acute

Keywords

Tenecteplase; TNK; MT; Mechanical Thrombectomy

Outcome Measures

Primary Outcomes (1)

• Distribution of the modified Rankin Scale scores at 90 days

  Distribution of the modified Rankin Scale scores (shift analysis).

  90 days

Secondary Outcomes (8)

• Functional independence defined as modified Rankin Score ≤ 2

  90 days

• Infarct volume evaluated on CT at 24 hours (-2/+12 hours).

  24 hours

• Dramatic early favorable response as determined by a National Institute of Health Stroke Scale (NIHSS) of 0-2 or NIHSS improvement ≥ 10 points at 24 (-2/+12 hours) hours.

  24 hours

• Cost-effectiveness analysis of endovascular therapy alone vs. endovascular therapy associated with tenecteplase

  12 months

• Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year among the groups

  3 months, 6 months and 12 months

Other Outcomes (4)

• Mortality at 90 days

  90 days

• Mortality related to stroke and complications at 90 days

  90 days

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

  24 hours

Study Arms (2)

Mechanical Thrombectomy preceded by TNK

EXPERIMENTAL

Subjects assigned to this arm will receive an intravenous bolus of tenecteplase (0.25mg/kg) before the mechanical thrombectomy.

Drug: Tenecteplase

Mechanical Thrombectomy preceded by Placebo

PLACEBO COMPARATOR

Subjects assigned to this arm will receive an intravenous bolus of matching placebo (with the same volume of infusion as of 0.25mg/kg of tenecteplase) before the mechanical thrombectomy.

Drug: Placebo

Interventions

Tenecteplase DRUG

Intravenous thrombolysis with tenecteplase 0.25mg/kg

Also known as: TNK

Mechanical Thrombectomy preceded by TNK

Placebo DRUG

Intravenous administration of placebo, matching the volume of tenecteplase 0.25mg/kg

Mechanical Thrombectomy preceded by Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute ischemic stroke where a patient is eligible for IV thrombolytic treatment within 4.5 hours of stroke onset.
• No significant pre-stroke functional disability (mRS ≤ 1)
• Baseline NIHSS scores obtained before randomization must be equal to or higher than 6 points
• Age equal ≥ 18 and =\< 85 years
• Occlusion (TICI 0-1) of the ICA or proximal MCA segments (M1 or M2) suitable for endovascular treatment, as evidenced by CTA, MRA, or angiogram, with or without concomitant cervical carotid stenosis or occlusion.
• Patient randomized within 4.5 hours of symptom onset. Symptoms onset is defined as the point in time the patient was last seen well (at baseline). Treatment start is defined as groin puncture, max 90 minutes after randomization.
• Patients who have woken up with the symptoms and who have a mismatch FLAIR-DWI according to the WAKE-UP Trial will be considered as having a time window of \<4.5h.
• Informed consent obtained from the patient or acceptable patient surrogate.

You may not qualify if:

• Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR \> 1.7 or direct oral anticoagulants such as thrombin antagonists (ex: dabigatran) or X factor (ex: rivaroxaban, apixaban, edoxaban) at the least 48 hours.
• Baseline platelet count \< 100.000/μL
• Baseline blood glucose of \< 50mg/dL or \> 400mg/dl
• Severe, sustained hypertension (SBP \> 185 mm Hg or DBP \> 110 mm Hg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using AHA guidelines recommended medication (including iv antihypertensive drips), the patient can be enrolled.
• Patients in coma (NIHSS item of consciousness \>1) (Intubated patients for transfer could be randomized only in case an NIHSS is obtained by a neurologist prior transportation).
• Seizures at stroke onset which would preclude obtaining a baseline NIHSS
• Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.
• History of life-threatening allergy (more than rash) to contrast medium.
• Subjects who has received IV t-PA treatment before the randomization.
• Renal failure with serum creatinine ≥ 3 mg/dl
• Woman of childbearing potential who is known to be pregnant or who has a positive pregnancy test on admission.
• Subject participating in a study involving an investigational drug or device that would impact this study.
• Cerebral vasculitis, endocarditis or subarachnoid hemorrhage.
• Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations.
• Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas).

Sponsors & Collaborators

• Hospital Moinhos de Vento: lead
• Ministry of Health, Brazil: collaborator
• Boehringer Ingelheim: collaborator
• Medtronic: collaborator

Study Sites (13)

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90035000, Brazil

RECRUITING

Hospital das Clínicas Botucatu

Botucatu, Brazil

RECRUITING

Hospital de Base do Distrito Federal

Brasília, Brazil

RECRUITING

Hospital das Clínicas da UFPR

Curitiba, Brazil

RECRUITING

Hospital Geral de Fortaleza

Fortaleza, Brazil

RECRUITING

Hospital de Clinicas de Porto Alegre

Porto Alegre, Brazil

RECRUITING

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto

Ribeirão Preto, Brazil

RECRUITING

Hospital de Base de Rio Preto

São José do Rio Preto, Brazil

RECRUITING

Hospital das Clínicas de São Paulo

São Paulo, Brazil

RECRUITING

Hospital Sao Paulo

São Paulo, Brazil

RECRUITING

Santa Casa de Misericordia de Sao Paulo

São Paulo, Brazil

RECRUITING

Hospital Universitário de Uberlândia

Uberlândia, Brazil

RECRUITING

Hospital Estadual Central

Vitória, Brazil

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Tenecteplase

Condition Hierarchy (Ancestors)

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

• Octavio M Pontes-Neto, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Sheila CO Martins, MD, PhD

  Hospital Moinhos de Vento

  PRINCIPAL INVESTIGATOR

• Raul G Nogueira, MD

  University of Pittsburgh Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Octavio M Pontes-Neto, MD, PhD

CONTACT

+551636053779; opontesneto@fmrp.usp.br

Leonardo A 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: January 6, 2022
• First Posted: January 20, 2022
• Study Start: May 27, 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 (13)