Comparing two treatments for acute ischemic stroke

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

This study is testing two different treatments for acute ischemic stroke to see which one helps patients recover better after 90 days.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 398 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Hospital Moinhos de Vento (Academic / other)
• Locations: 13 sites (Porto Alegre, Rio Grande do Sul and 12 other locations)
• Trial ID: NCT05199194 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial investigates two treatment strategies for acute ischemic stroke caused by a large vessel occlusion. Participants will be randomly assigned to receive either direct mechanical thrombectomy or mechanical thrombectomy preceded by intravenous tenecteplase. The study aims to evaluate the effectiveness of these approaches in improving patient outcomes, measured by the modified Rankin scale score at 90 days post-treatment. The trial will include a diverse group of participants across multiple centers, ensuring robust data collection and analysis.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 85 who have experienced an acute ischemic stroke within 4.5 hours and are eligible for intravenous thrombolysis.

Not a fit: Patients with significant pre-stroke functional disability or those outside the age range of 18 to 85 may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options for patients suffering from acute ischemic stroke.

How similar studies have performed: Other studies have shown promising results with similar thrombolytic approaches, indicating potential for success in this trial.

Eligibility criteria

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.

  * 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.

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).

Where this trial is running

Porto Alegre, Rio Grande do Sul and 12 other locations

• Hospital Moinhos de Vento — Porto Alegre, Rio Grande do Sul, 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)

Study contacts

• Principal investigator: Octavio M Pontes-Neto, MD, PhD — Hospital de Clínicas da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo
• Study coordinator: Octavio M Pontes-Neto, MD, PhD

Conditions Stroke, Ischemic; Stroke, Acute; Tenecteplase; TNK; MT; Mechanical Thrombectomy