Stroke, IschemicPhase 3DIRECT-TNKNCT05199194
Randomization to Endovascular Treatment Alone or Preceded by Systemic Thrombolysis With Tenecteplase in Ischemic Stroke
A Phase 3 study testing Tenecteplase in people with Stroke, Ischemic and Stroke, Acute, run by Hospital Moinhos de Vento at 13 sites in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Stroke, Ischemic, Stroke, Acute
- What is being tested?
- Tenecteplase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 398 participants
- Where
- 13 sitesBrazil
- Study dates
- 27 May 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 22Show fewer
- 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).
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
Brazil13 sites, 13 recruiting
- Recruiting
Hospital das Clínicas Botucatu
Botucatu
Rodrigo Bazan, MD
- Recruiting
Hospital de Base do Distrito Federal
Brasília
Leticia Rebello
- Recruiting
Hospital das Clínicas da UFPR
Curitiba
Viviane Zetola
- Recruiting
Hospital Geral de Fortaleza
Fortaleza
Francisco Mont'Alverne, MD
- Recruiting
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035000
Sheila Martins
- Recruiting
Hospital de Clinicas de Porto Alegre
Porto Alegre
Rosane Brondani
- Recruiting
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
Ribeirão Preto
Otavio Pontes Neto, MD
- Recruiting
Hospital de Base de Rio Preto
São José do Rio Preto
Raquel Hidalgo
- Recruiting
Hospital das Clínicas de São Paulo
São Paulo
Guilherme Diogo
- Recruiting
Hospital Sao Paulo
São Paulo
Gisele Sampaio
- Recruiting
Santa Casa de Misericordia de Sao Paulo
São Paulo
Rubens Gagliardi
- Recruiting
Hospital Universitário de Uberlândia
Uberlândia
Jullyanna Shinosaki
- Recruiting
Hospital Estadual Central
Vitória
José Fiorot JR, MD
About this study
Official title: 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.
Read the detailed description
Randomized, prospective, multicenter, double-blinded, placebo-controlled clinical trial with adaptive desing. 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).
Subjects presenting acute ischemic stroke within 4.5 hours of the onset of symptoms attributable to an occlusion of intracranial internal carotid or of the proximal middle cerebral artery (MCA, M1- or M2-segment) with or without tandem occlusion of cervical internal carotid confirmed by vascular neuroimaging. Subjects should be eligible for IV thrombolysis. In the sample size calculation, a difference in treatment effect between the groups (achievement of mRS 0 to 2 at 90 days) of 10.6% was considered, with 33.8% in the intervention group (TNK + thrombectomy) and 23.2% in the control group (placebo + thrombectomy), using a unilateral alpha of 0.025, with a power of 80%, resulting in a sample size of 358 participants. Considering a loss ratio of 10%, a sample size of 398 participants is estimated (199 in each treatment arm). An interim analysis is planned to be executed with 50% and 75% of the total sample. It allows the trial to be terminated in the case of efficacy or futility, in addition to enabling adaptive designed based on conditional probability of a positive result.
- Conditions
- Stroke, Ischemic, Stroke, Acute
- Being tested
- Tenecteplase, Placebo
- Keywords
- Tenecteplase, TNK, MT, Mechanical Thrombectomy
- Medical subject headings
- Ischemic Stroke, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TenecteplaseDrug
Also called TNK
Intravenous thrombolysis with tenecteplase 0.25mg/kg
PlaceboDrug
Intravenous administration of placebo, matching the volume of tenecteplase 0.25mg/kg
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Distribution of the modified Rankin Scale scores at 90 days
Distribution of the modified Rankin Scale scores (shift analysis).
Measured: 90 days
Secondary outcomes (8)
Functional independence defined as modified Rankin Score ≤ 2
Functional independence defined as modified Rankin Score ≤ 2
Measured: 90 days
Infarct volume evaluated on CT at 24 hours (-2/+12 hours).
Infarct volume evaluated on CT at 24 hours (-2/+12 hours).
Measured: 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.
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.
Measured: 24 hours
Cost-effectiveness analysis of endovascular therapy alone vs. endovascular therapy associated with tenecteplase
Cost-effectiveness analysis of endovascular therapy alone vs. endovascular therapy associated with tenecteplase
Measured: 12 months
Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year among the groups
Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year among the groups
Measured: 3 months, 6 months and 12 months
Score distribution of mRS at 90 days (shift analysis) in patients presenting M2-CMA occlusion
Score distribution of mRS at 90 days (shift analysis) in patients presenting M2-CMA occlusion
Measured: 90 days
Vessel recanalization evaluated by CT angiography or MRA at 24 hours in both treatment groups
Vessel recanalization evaluated by CT angiography or MRA at 24 hours in both treatment groups
Measured: 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.
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.
Measured: Immediately Post-procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2022
- Study start27 May 2022
- Primary completionJul 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stroke, IschemicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 398 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Moinhos de Vento
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Brazil, Boehringer Ingelheim, Medtronic
- Responsible party
- Sponsor
- Investigators
- Octavio M Pontes-Neto, MD, PhD, Principal investigator, Hospital de Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São PauloSheila CO Martins, MD, PhD, Principal investigator, Hospital Moinhos de VentoRaul G Nogueira, MD, Principal investigator, University of Pittsburgh Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05199194
- Sponsor's protocol ID
- RESILIENT DIRECT-TNK
- Acronym
- DIRECT-TNK
- Status last verified
- Apr 2025
- First submitted
- 6 Jan 2022
- Last updated
- 4 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05199194
- Acronym / sponsor ID
- DIRECT-TNK / RESILIENT DIRECT-TNK
- Conditions
- Stroke, Ischemic, Stroke, Acute
- Keywords
- Tenecteplase, TNK, MT, Mechanical Thrombectomy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 398 participants (estimated)
- Lead sponsor
- Hospital Moinhos de VentoUniversity, hospital or other
- Collaborators
- Ministry of Health, Brazil, Boehringer Ingelheim, Medtronic
- Study start
- 27 May 2022 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 20 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Randomized, prospective, multicenter, double-blinded, placebo-controlled clinical trial with adaptive desing. 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).
Subjects presenting acute ischemic stroke within 4.5 hours of the onset of symptoms attributable to an occlusion of intracranial internal carotid or of the proximal middle cerebral artery (MCA, M1- or M2-segment) with or without tandem occlusion of cervical internal carotid confirmed by vascular neuroimaging. Subjects should be eligible for IV thrombolysis. In the sample size calculation, a difference in treatment effect between the groups (achievement of mRS 0 to 2 at 90 days) of 10.6% was considered, with 33.8% in the intervention group (TNK + thrombectomy) and 23.2% in the control group (placebo + thrombectomy), using a unilateral alpha of 0.025, with a power of 80%, resulting in a sample size of 358 participants. Considering a loss ratio of 10%, a sample size of 398 participants is estimated (199 in each treatment arm). An interim analysis is planned to be executed with 50% and 75% of the total sample. It allows the trial to be terminated in the case of efficacy or futility, in addition to enabling adaptive designed based on conditional probability of a positive result.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mechanical Thrombectomy preceded by TNK | Experimental | Drug: TenecteplaseSubjects assigned to this arm will receive an intravenous bolus of tenecteplase (0.25mg/kg) before the mechanical thrombectomy. |
| Mechanical Thrombectomy preceded by Placebo | Placebo comparator | Drug: PlaceboSubjects 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (22 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TenecteplaseAlso: TNKIntravenous thrombolysis with tenecteplase 0.25mg/kg | Drug | Mechanical Thrombectomy preceded by TNK |
| PlaceboIntravenous administration of placebo, matching the volume of tenecteplase 0.25mg/kg | Drug | Mechanical Thrombectomy preceded by Placebo |
Primary outcome
Distribution of the modified Rankin Scale scores at 90 days
Time frame: 90 days
Distribution of the modified Rankin Scale scores (shift analysis).
8 secondary outcomes
Functional independence defined as modified Rankin Score ≤ 2
Time frame: 90 days
Infarct volume evaluated on CT at 24 hours (-2/+12 hours).
Time frame: 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
Cost-effectiveness analysis of endovascular therapy alone vs. endovascular therapy associated with tenecteplase
Time frame: 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
Score distribution of mRS at 90 days (shift analysis) in patients presenting M2-CMA occlusion
Time frame: 90 days
Vessel recanalization evaluated by CT angiography or MRA at 24 hours in both treatment groups
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Octavio M Pontes-Neto, MD, PhD principal investigator
Hospital de Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo
Sheila CO Martins, MD, PhD principal investigator
Hospital Moinhos de Vento
Raul G Nogueira, MD principal investigator
University of Pittsburgh Medical College
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tenecteplase in people with Stroke, Ischemic and Stroke, Acute, run by Hospital Moinhos de Vento at 13 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 8 inclusion and 22 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 13 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 Octavio M Pontes-Neto, MD, PhD (+551636053779, opontesneto@fmrp.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Distribution of 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?
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.