- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05199194
Randomization to Endovascular Treatment Alone or Preceded by Systemic Thrombolysis With Tenecteplase in Ischemic Stroke (DIRECT-TNK)
January 29, 2024 updated by: Hospital Moinhos de Vento
Randomization to EndoVascular Treatment Alone or Preceded by Systemic Thrombolysis With Tenecteplase in Acute Ischemic Stroke Due to Large Intracranial VEssel OcclusioN Trial - DIRECT Thrombectomy vs. Intravenous TNK Plus Thrombectomy
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
Randomized, prospective, multicenter, double-blinded, placebo-controlled clinical trial.
Randomization will be 1:1 according to reperfusion treatment modalities: (A) (with placebo TNK) direct mechanical thrombectomy vs. (B) Intravenous thrombolysis with TNK (0.25 mg/kg) plus mechanical thrombectomy.
Randomization will be done by a minimization process using age, National Institute of Health Stroke Scale (NIHSS) score, and site of the occluded artery.
For the primary outcome, the subjects will be followed up within 90 days after randomization.
The primary outcome will be the ordinal distribution from the modified Rankin scale score (mRS).
Study Type
Interventional
Enrollment (Estimated)
390
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Octavio M Pontes-Neto, MD, PhD
- Phone Number: +551636053779
- Email: opontesneto@fmrp.usp.br
Study Contact Backup
- Name: Leonardo A Carbonera, MD, MSc
- Phone Number: +555135378195
- Email: leonardo.carbonera@hmv.org.br
Study Locations
-
-
-
Botucatu, Brazil
- Recruiting
- Hospital das Clínicas Botucatu
-
Contact:
- Rodrigo Bazan, MD
-
Brasília, Brazil
- Recruiting
- Hospital de Base do Distrito Federal
-
Contact:
- Leticia Rebello
-
Curitiba, Brazil
- Recruiting
- Hospital das Clínicas da UFPR
-
Contact:
- Viviane Zetola
-
Fortaleza, Brazil
- Recruiting
- Hospital Geral de Fortaleza
-
Contact:
- Francisco Mont'Alverne, MD
-
Porto Alegre, Brazil
- Recruiting
- Hospital de Clinicas de Porto Alegre
-
Contact:
- Rosane Brondani
-
Ribeirão Preto, Brazil
- Recruiting
- Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
-
Contact:
- Otavio Pontes Neto, MD
-
São José Do Rio Preto, Brazil
- Recruiting
- Hospital de Base de Rio Preto
-
Contact:
- Raquel Hidalgo
-
São Paulo, Brazil
- Recruiting
- Hospital das Clínicas de São Paulo
-
Contact:
- Guilherme Diogo
-
São Paulo, Brazil
- Recruiting
- Hospital Sao Paulo
-
Contact:
- Gisele Sampaio
-
São Paulo, Brazil
- Recruiting
- Santa Casa de Misericordia de Sao Paulo
-
Contact:
- Rubens Gagliardi
-
Uberlândia, Brazil
- Recruiting
- Hospital Universitário de Uberlândia
-
Contact:
- Jullyanna Shinosaki
-
Vitória, Brazil
- Recruiting
- Hospital Estadual Central
-
Contact:
- José Fiorot JR, MD
-
-
Rio Grande Do Sul
-
Porto Alegre, Rio Grande Do Sul, Brazil, 90035000
- Recruiting
- Hospital Moinhos de Vento
-
Contact:
- Sheila Martins
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 85 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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.
- Informed consent obtained from the patient or acceptable patient surrogate.
Exclusion Criteria:
- 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).
- Hypodensity on CT more than one third of MCA territory or hypersignal in more than one third of MCA territory on MR-DWI.
- ASPECTS score < 6 (no contrast at least 5 mm cut imaging on CT) or on MR-DWI sequence.
- CT or MR evidence of hemorrhage (the presence of < 5 GRE, SWI, SWAN microbleeds is allowed).
- Significant mass effect with midline shift.
- Evidence of ipsilateral carotid occlusion, high grade stenosis or arterial dissection in the extracranial or petrous segment of the internal carotid artery that cannot be treated or will prevent access to the intracranial clot or excessive tortuosity of cervical vessels precluding device delivery/deployment.
- Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation).
- Evidence of intracranial tumor (except small meningioma).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Mechanical Thrombectomy preceded by TNK
Subjects assigned to this arm will receive an intravenous bolus of tenecteplase (0.25mg/kg) before the mechanical thrombectomy.
|
Intravenous thrombolysis with tenecteplase 0.25mg/kg
Other Names:
|
Placebo Comparator: Mechanical Thrombectomy preceded by Placebo
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.
|
Intravenous administration of placebo, matching the volume of tenecteplase 0.25mg/kg
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Distribution of the modified Rankin Scale scores at 90 days
Time Frame: 90 days
|
Distribution of the modified Rankin Scale scores (shift analysis).
|
90 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Functional independence defined as modified Rankin Score ≤ 2
Time Frame: 90 days
|
Functional independence defined as modified Rankin Score ≤ 2
|
90 days
|
Infarct volume evaluated on CT at 24 hours (-2/+12 hours).
Time Frame: 24 hours
|
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.
Time Frame: 24 hours
|
Dramatic early favorable response as determined by a National Institute of Health Stroke Scale 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
Time Frame: 12 months
|
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
Time Frame: 3 months, 6 months and 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
|
Score distribution of mRS at 90 days (shift analysis) in patients presenting M2-CMA occlusion
Time Frame: 90 days
|
Score distribution of mRS at 90 days (shift analysis) in patients presenting M2-CMA occlusion
|
90 days
|
Vessel recanalization evaluated by CT angiography or MRA at 24 hours in both treatment groups
Time Frame: 24 hours
|
Vessel recanalization evaluated by CT angiography or MRA at 24 hours in both treatment groups
|
24 hours
|
Vessel recanalization post procedure in the endovascular arm assessed by TIMI grades and adjudicated by a central core-lab. Successful recanalization is defined as TICI (Thrombolysis in Cerebral Infarction) 2b or 3 on the post-procedure angiogram.
Time Frame: Immediately Post-procedure
|
Vessel recanalization post procedure in the endovascular arm assessed by TIMI grades and adjudicated by a central core-lab.
Successful recanalization is defined as TICI (Thrombolysis in Cerebral Infarction) 2b or 3 on the post-procedure angiogram.
|
Immediately Post-procedure
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality at 90 days
Time Frame: 90 days
|
Mortality at 90 days
|
90 days
|
Mortality related to stroke and complications at 90 days
Time Frame: 90 days
|
Mortality related to stroke and complications at 90 days
|
90 days
|
Clinically significant ICH rates at 24 (-2/+12) hours.
Time Frame: 24 hours
|
All intracerebral hemorrhages will be classified by a central core-lab using the ECASS criteria.
Symptomatic ICH will be defined as per the SITS-MOST definition: deterioration in NIHSS score of ≥4 points within 24 hours from treatment and evidence of intraparenchymal hemorrhage type 2 in the 22 to 36 hours follow-up imaging scans.
The incidence of any asymptomatic hemorrhage measured at 24 (-2/+12) hours will also be compared.
|
24 hours
|
Procedural related complications
Time Frame: 7 days
|
arterial perforation, arterial dissection, and embolization in a previously uninvolved vascular territory
|
7 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Sheila CO Martins, MD, PhD, Hospital Moinhos de Vento
- Principal Investigator: Octavio M Pontes-Neto, MD, PhD, Hospital de Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo
- Principal Investigator: Raul G Nogueira, MD, University of Pittsburgh Medical College
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 27, 2022
Primary Completion (Estimated)
July 1, 2026
Study Completion (Estimated)
July 1, 2027
Study Registration Dates
First Submitted
January 6, 2022
First Submitted That Met QC Criteria
January 6, 2022
First Posted (Actual)
January 20, 2022
Study Record Updates
Last Update Posted (Actual)
January 30, 2024
Last Update Submitted That Met QC Criteria
January 29, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RESILIENT DIRECT-TNK
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Stroke, Ischemic
-
Nordsjaellands HospitalRigshospitalet, Denmark; Metropolitan University CollegeCompletedTransient Ischemic Attack | Stroke, Ischemic | Stroke HemorrhagicDenmark
-
University of CalgaryThe George Institute for Global Health, AustraliaNot yet recruitingAcute Ischemic Stroke AIS | Stroke, Acute, Stroke Ischemic | Stroke AcuteCanada, Australia
-
Second Affiliated Hospital, School of Medicine,...Shanghai Zhongshan Hospital; First Affiliated Hospital of Wenzhou Medical University and other collaboratorsRecruitingAcute Ischemic Stroke and Transient Ischemic AttacksChina
-
Medtronic Cardiac Rhythm and Heart FailureMedtronic Bakken Research CenterCompletedCryptogenic Symptomatic Transient Ischemic Attack | Cryptogenic Ischemic StrokeNetherlands, United States, France, Belgium, Germany, Sweden, Italy, Austria, Canada, Denmark, Finland, Greece, Slovakia, Spain
-
University Hospital, BrestCompletedStroke, Ischemic | Stroke HemorrhagicFrance
-
Umbria Bioengineering TechnologiesRecruitingStroke, Ischemic | Stroke HemorrhagicItaly
-
Sheffield Teaching Hospitals NHS Foundation TrustUnknownFatigue | Stroke, Ischemic | Stroke HemorrhagicUnited Kingdom
-
BayerRecruitingAcute Non-cardioembolic Ischemic Stroke | Prevention of Ischemic Stroke | High-risk Transient Ischemic AttackUnited States, Switzerland, Belgium, Australia, Sweden, Canada, Taiwan, Spain, Korea, Republic of, Latvia, Israel, Malaysia, China, Greece, Japan, Turkey, Netherlands, Romania, United Kingdom, Portugal, Hungary, Italy, Brazil, France, S... and more
-
University of AlbertaCompletedTransient Ischemic Attack | Minor Ischemic StrokeCanada
-
Ischemia Care LLCCompletedIschemic Stroke | Atrial Fibrillation | Thrombotic Stroke | Transient Ischemic Attacks | Cardioembolic Stroke | Stroke of Basilar Artery | Transient Cerebrovascular EventsUnited States
Clinical Trials on Tenecteplase
-
Kaiser PermanenteGenentech, Inc.TerminatedPleural EffusionUnited States
-
Huashan HospitalShanghai 10th People's Hospital; Shanghai East Hospital; The Second Affiliated... and other collaboratorsCompleted
-
Boehringer IngelheimTerminatedHeart ArrestGermany, Belgium, Sweden, France, Austria, Italy, Norway, Spain, Switzerland
-
Genentech, Inc.CompletedDysfunctional Central Venous Access Catheters
-
University Of PerugiaTerminated
-
The George InstituteUniversity of Calgary; Berry ConsultantsNot yet recruiting
-
Genentech, Inc.CompletedDysfunctional Central Venous Access Catheters
-
Genentech, Inc.CompletedDysfunctional Hemodialysis Catheters
-
General Hospital of Shenyang Military RegionCompleted
-
Second Affiliated Hospital of Guangxi Medical UniversityCSPC Pharmaceutical Group LimitedNot yet recruiting