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

NCT ID: NCT04256096

Last Updated: 2021-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

376 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-09

Study Completion Date

2022-05-01

Brief Summary

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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

Detailed Description

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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.

Conditions

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Stroke, Ischemic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The randomization employs a 1:1 ratio of mechanical thrombectomy with stent-retriever and/or thromboaspiration versus medical management alone
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Sham endovascular procedure has been rejected due to the medical risk of the angiography and practical issues that difficult to maintain blindness of investigators. For the primary endpoint, subjects will be followed for 90 days post-randomization. Distribution of the modified Rankin Scale scores at 90 days will be evaluated by two separate assessors who are blinded to treatment. Primary Endpoint will consider central core lab readings only (video interview with RFA method) with local reading as a back-up mechanism.

Study Groups

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thrombectomy

mechanical thrombectomy with stent-retriever and/or thromboaspiration

Group Type EXPERIMENTAL

Thrombectomy

Intervention Type DEVICE

Endovascular treatment of large vessel occlusion (mechanical thrombectomy) with stent-retriever and/or thromboaspiration (neurointerventionalist choice)

Clinical treatment

Best Medical treatment

Group Type ACTIVE_COMPARATOR

Thrombectomy

Intervention Type DEVICE

Endovascular treatment of large vessel occlusion (mechanical thrombectomy) with stent-retriever and/or thromboaspiration (neurointerventionalist choice)

Interventions

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Thrombectomy

Endovascular treatment of large vessel occlusion (mechanical thrombectomy) with stent-retriever and/or thromboaspiration (neurointerventionalist choice)

Intervention Type DEVICE

Other Intervention Names

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Endovascular treatment

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital das Clínicas de Ribeirão Preto

OTHER

Sponsor Role collaborator

Hospital Geral de Fortaleza

OTHER_GOV

Sponsor Role collaborator

Hospital de Base

OTHER

Sponsor Role collaborator

Federal University of São Paulo

OTHER

Sponsor Role collaborator

Fundação Faculdade Regional de Medicina de São José do Rio Preto

OTHER

Sponsor Role collaborator

UPECLIN HC FM Botucatu Unesp

OTHER

Sponsor Role collaborator

University of Campinas, Brazil

OTHER

Sponsor Role collaborator

Irmandade Santa Casa de Misericórdia de Porto Alegre

OTHER

Sponsor Role collaborator

Universidade Federal do Paraná

OTHER

Sponsor Role collaborator

Hospital Estadual Central

UNKNOWN

Sponsor Role collaborator

Hospital Sao Jose do Avai

UNKNOWN

Sponsor Role collaborator

Irmandade da Santa Casa de Misericordia de Sao Paulo

OTHER

Sponsor Role collaborator

Federal University of Uberlandia

OTHER

Sponsor Role collaborator

Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo

OTHER

Sponsor Role collaborator

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role lead

Responsible Party

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SHEILA CRISTINA OURIQUES MARTINS

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Raul G Nogueira, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Sheila CO Martins, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Clinicas de Porto Alegre

Locations

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Hospital Geral de Fortaleza

Fortaleza, Ceará, Brazil

Site Status RECRUITING

Associacao Congregacao de Santa Catarina

Vitória, Espírito Santo, Brazil

Site Status RECRUITING

Hospital de Base

Brasília, Federal District, Brazil

Site Status RECRUITING

Hospital das Clínicas de Uberlândia

Uberlândia, Minas Gerais, Brazil

Site Status RECRUITING

Hospital de Clínicas da Universidade Federal do Paraná

Curitiba, Paraná, Brazil

Site Status NOT_YET_RECRUITING

Conferencia Sao jose do Avai

Itaperuna, Rio de Janeiro, Brazil

Site Status NOT_YET_RECRUITING

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status RECRUITING

Irmandade da Santa Casa de Misericordia de Porto Alegre - ISCMPA

Porto Alegre, Rio Grande do Sul, Brazil

Site Status NOT_YET_RECRUITING

Hospital das Clínicas da Faculdade de Medicina de Botucatu

Botucatu, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

Hospital de Clínicas - UNICAMP

Campinas, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

Hospital das Clinicas de Ribeirao Preto

Ribeirão Preto, São Paulo, Brazil

Site Status RECRUITING

Fundacao Faculdade Regional de Medicina S J Rio Preto

São José do Rio Preto, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

Instituto de Assistência Médica ao Servidor Público Estadual de Sao Paulo

São Paulo, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

Universidade Federal de São Paulo - UNIFESP/EPM

São Paulo, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

Countries

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Brazil

Central Contacts

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Sheila CO Martins, MD, PhD

Role: CONTACT

51999628467

Natacha Fleck

Role: CONTACT

51992699829

Facility Contacts

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Fabricio Lima, PhD

Role: primary

85999982150

Jose A Fiorot Jr, PhD

Role: primary

27992778579

Leticia C Rebello, MD

Role: primary

61999150626

Jullyanna Shinosaki, MD

Role: primary

+553491161478

Viviane F Zetola

Role: primary

0154199761660

Ivete itaperuna P Goncalves

Role: primary

22988315201

Natacha Fleck

Role: primary

51992699829

Ana Julia Lehnen

Role: backup

51992870762

Alexandre Maulaz

Role: primary

51992826915

Rodrigo Bazan, PhD

Role: primary

14981157727

Fabricio B Cardoso, MD

Role: primary

019981254952

Octavio M Pontes-Neto, PhD

Role: primary

16981013465

Raquel Hidalgo, MD

Role: primary

17997640004

André Rezende, MD

Role: primary

+5511981359842

Gisele S Silva, PhD

Role: primary

References

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Roaldsen MB, Lindekleiv H, Mathiesen EB. Intravenous thrombolytic treatment and endovascular thrombectomy for ischaemic wake-up stroke. Cochrane Database Syst Rev. 2021 Dec 1;12(12):CD010995. doi: 10.1002/14651858.CD010995.pub3.

Reference Type DERIVED
PMID: 34850380 (View on PubMed)

Other Identifiers

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17877519.6.1001.5327

Identifier Type: -

Identifier Source: org_study_id

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