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Randomization of Endovascular Treatment in Acute Ischemic Stroke in the Extended Time Window (RESILIENTExt)

H

Hospital de Clinicas de Porto Alegre

Status and phase

Unknown
Phase 3

Conditions

Stroke, Ischemic

Treatments

Device: Thrombectomy

Study type

Interventional

Funder types

Other

Identifiers

NCT04256096
17877519.6.1001.5327

Details and patient eligibility

About

A phase III, randomized, multi-center, open label clinical trial that will examine whether endovascular treatment is superior to standard medical therapy alone in patients who suffer a large vessel anterior circulation ischemic stroke within 8-24 hours from time last seen well

Full description

Prospective, multi-center, randomized, controlled, open-label, blinded-endpoint trial with a sequential design. The randomization employs a 1:1 ratio of mechanical thrombectomy with stent-retriever and/or thromboaspiration versus medical management alone in patients who suffer a large vessel anterior circulation ischemic stroke between 8 and 24 hours from time last seen well. Randomization will be done under a minimization process using age (≤68 vs. >68 years), baseline NIHSS (<17 v. ≥17), ASPECTS (5-7 vs. 8-10), therapeutic window (6-12 or 12-24 hours after TLKW), occlusion site (Intracranial ICA or M1), and clinical site. For the primary endpoint, subjects will be followed for 90 days post-randomization. Sham endovascular procedure has been rejected due to the medical risk of the angiography and practical issues that difficult to maintain blindness of investigators.

Enrollment

376 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Acute ischemic stroke where patient is ineligible for IV thrombolytic treatment or the treatment is contraindicated (e.g., subject presents beyond recommended time from symptom onset), or where patient has received IV thrombolytic therapy without clinical improvement.

  2. No significant pre-stroke functional disability (mRS ≤2)

  3. Baseline NIHSS score obtained prior to randomization must be equal or higher than 8 points (assessed within one hour prior to qualifying imaging)

  4. Age ≥18 years (no upper age limit)

  5. Occlusion (TICI 0-1) of the intracranial ICA (distal ICA or T occlusions) and/or MCA-M1 segment suitable for endovascular treatment, as evidenced by CTA, MRA or angiogram, with or without concomitant cervical carotid occlusion or stenosis.

  6. The presence of Age-Adjusted modified Clinical ASPECTS Mismatch (mCAM) defined as ASPECTS 5-10 and one of the following criteria:

    1. NIHSS ≥ 8 and >50% involvement in 0-1 Cortical (e.g. M1-6) ASPECTS areas (any age);
    2. NIHSS ≥ 8 and >50% involvement in 0-2 Cortical (e.g. M1-6) ASPECTS areas (and age < 80 years old);
    3. NIHSS ≥ 15 and >50% involvement in 0-3 Cortical (e.g. M1-6) ASPECTS areas (and age < 80 years old).
  7. Patient treatable within 6-24 hours of symptom onset. Symptoms onset is defined as point in time the patient was last seen well (at baseline). Treatment start is defined as arterial puncture.

  8. Informed consent obtained from patient or acceptable patient surrogate

Exclusion criteria

-Clinical criteria

  1. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 3.0

  2. Baseline platelet count < 30.000/µL

  3. Baseline blood glucose of < 50mg/dL

  4. 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.

  5. Patients in coma defined as totally unresponsive; responding only with reflexes or being areflexic (Intubated patients for transfer could be randomized only in case an NIHSS is obtained by a neurologist prior transportation).

  6. Seizures at stroke onset which would preclude obtaining a baseline NIHSS

  7. Serious, advanced, or terminal illness with anticipated life expectancy of less than one year.

  8. History of life-threatening allergy (more than rash) to contrast medium

  9. Subjects who has received IV t-PA treatment beyond 4.5 hours from the beginning of the symptoms

  10. Woman of childbearing potential who is known to be pregnant or who has a positive pregnancy test on admission.

  11. Subject participating in a study involving an investigational drug or device that would impact this study.

  12. Cerebral vasculitis

  13. Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤2. This excludes patients who are severely demented, require constant assistance in a nursing home type setting or who live at home but are not fully independent in activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.)

  14. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas).

    • Neuroimaging criteria
  15. Hypodensity on CT or restricted diffusion on MRI amounting to an ASPECTS score of <5.

  16. Complete involvement of more than 3 cortical ASPECTS areas (e.g. M1, M2, M3, M4, M5, or M6).

  17. Complete absence of leptomeningeal collaterals on CT angiography (e.g. Malignant CTA pattern or score 0).

  18. CT or MR evidence of hemorrhage (the presence of GRE microbleeds is allowed).

  19. Significant mass effect with midline shift.

  20. 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

  21. Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)

  22. Evidence of intracranial tumor (except small meningioma).

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

376 participants in 2 patient groups

thrombectomy
Experimental group
Description:
mechanical thrombectomy with stent-retriever and/or thromboaspiration
Treatment:
Device: Thrombectomy
Clinical treatment
Active Comparator group
Description:
Best Medical treatment
Treatment:
Device: Thrombectomy

Trial contacts and locations

14

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Central trial contact

Sheila CO Martins, MD, PhD; Natacha Fleck

Data sourced from clinicaltrials.gov

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