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

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ClinicalTrials.gov Identifier: NCT04256096
Recruitment Status : Recruiting
First Posted : February 5, 2020
Last Update Posted : February 10, 2021
Sponsor:
Collaborators:
Hospital das Clínicas de Ribeirão Preto
Hospital Geral de Fortaleza
Hospital de Base
Federal University of São Paulo
Fundação Faculdade Regional de Medicina de São José do Rio Preto
UPECLIN HC FM Botucatu Unesp
University of Campinas, Brazil
Irmandade Santa Casa de Misericórdia de Porto Alegre
Universidade Federal do Paraná
Hospital Estadual Central
Hospital Sao Jose do Avai
Irmandade da Santa Casa de Misericordia de Sao Paulo
Federal University of Uberlandia
Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo
Information provided by (Responsible Party):
SHEILA CRISTINA OURIQUES MARTINS, Hospital de Clinicas de Porto Alegre

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Stroke, Ischemic Device: Thrombectomy Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 376 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The randomization employs a 1:1 ratio of mechanical thrombectomy with stent-retriever and/or thromboaspiration versus medical management alone
Masking: Single (Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Randomization of Endovascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke Due to Large VEssel OcclusioN Trial in the Extended Time Window
Actual Study Start Date : March 9, 2020
Estimated Primary Completion Date : February 1, 2022
Estimated Study Completion Date : May 1, 2022

Arm Intervention/treatment
Experimental: thrombectomy
mechanical thrombectomy with stent-retriever and/or thromboaspiration
Device: Thrombectomy
Endovascular treatment of large vessel occlusion (mechanical thrombectomy) with stent-retriever and/or thromboaspiration (neurointerventionalist choice)
Other Name: Endovascular treatment

Active Comparator: Clinical treatment
Best Medical treatment
Device: Thrombectomy
Endovascular treatment of large vessel occlusion (mechanical thrombectomy) with stent-retriever and/or thromboaspiration (neurointerventionalist choice)
Other Name: Endovascular treatment




Primary Outcome Measures :
  1. Modified Rankin Scale scores [ Time Frame: 90 days ]
    Distribution of the modified Rankin Scale scores at 90 days (shift analysis). The score range from zero to 6 with higher values indicating a worst functional outcome at 90 days


Secondary Outcome Measures :
  1. Proportion of Patients with Functional independence in 90 days [ Time Frame: 90 days ]
    Functional independence defined as mRS ≤2

  2. Disability on the utility-weighted modified Rankin scale (UW-mRS) [ Time Frame: 90 days ]
    Mean score for disability on the utility-weighted modified Rankin scale (UW-mRS). The score range from 1 to zero with higher values indicating a better functional outcome at 90 days

  3. Quality of life measured by EuroQol Group 5-Dimension Self-Report Questionnaire (EuroQol / EQ5D) [ Time Frame: 90 days and 1 year ]
    Quality of life analysis as measured by EuroQol/EQ5D 5-Dimension Self-Report Questionnaire, on which scores range from -0.176 to 1, with higher values indicating a better quality of life]) at 90 days

  4. Mortality at 90 days [ Time Frame: 90 days ]
    Mortality at 90 days

  5. Proportion of patients with Intracranial Hemorrhage at 24 hours [ Time Frame: 24 hours ]
    Clinically significant ICH rates at 24 (-2/+12) hours. All intracerebral hemorrhages will be classified by a central core-lab using the Heidelberg 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.

  6. Procedural related complications [ Time Frame: immediately after procedure ]
    Procedural related complications: arterial perforation, arterial dissection, and embolization in a previously uninvolved vascular territory



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04256096


Contacts
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Contact: Sheila CO Martins, MD, PhD 51999628467 scmartins@hcpa.edu.br
Contact: Natacha Fleck 51992699829 pesquisaneurovascular@gmail.com

Locations
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Brazil
Hospital Geral de Fortaleza Recruiting
Fortaleza, Ceara, Brazil
Contact: Fabricio Lima, PhD    85999982150    fabricio.lima.neuro@gmail.com   
Hospital de Base Recruiting
Brasília, DF, Brazil
Contact: Leticia C Rebello, MD    61999150626    letirebello@gmail.com   
Associacao Congregacao de Santa Catarina Recruiting
Vitória, Espirito Santo, Brazil, 29050-335
Contact: Jose A Fiorot Jr, PhD    27992778579    fiorotjr@gmail.com   
Hospital das Clínicas de Uberlândia Recruiting
Uberlândia, Minas Gerais, Brazil
Contact: Jullyanna Shinosaki, MD    +553491161478    jsm_shinosaki@yahoo.com.br   
Hospital de Clínicas da Universidade Federal do Paraná Not yet recruiting
Curitiba, Parana, Brazil
Contact: Viviane F Zetola    0154199761660    viviane.zetola@gmail.com   
Conferencia Sao jose do Avai Not yet recruiting
Itaperuna, RJ, Brazil
Contact: Ivete itaperuna P Goncalves    22988315201    ipilloster@gmail.com   
Hospital de Clinicas de Porto Alegre Recruiting
Porto Alegre, RS, Brazil, 90035007
Contact: Natacha Fleck    51992699829    pesquisaneurovascular@gmail.com   
Contact: Ana Julia Lehnen    51992870762    anajlehnen@gmail.com   
Irmandade da Santa Casa de Misericordia de Porto Alegre - ISCMPA Not yet recruiting
Porto Alegre, RS, Brazil
Contact: Alexandre Maulaz    51992826915    maulaz@terra.com.br   
Hospital das Clínicas da Faculdade de Medicina de Botucatu Not yet recruiting
Botucatu, SP, Brazil
Contact: Rodrigo Bazan, PhD    14981157727    bazan.r@terra.com.br   
Hospital de Clínicas - UNICAMP Not yet recruiting
Campinas, SP, Brazil
Contact: Fabricio B Cardoso, MD    019981254952    fabriciobuchdid@hotmail.com   
Hospital das Clinicas de Ribeirao Preto Recruiting
Ribeirão Preto, SP, Brazil
Contact: Octavio M Pontes-Neto, PhD    16981013465    ompneto@gmail.com   
Fundacao Faculdade Regional de Medicina S J Rio Preto Not yet recruiting
São José Do Rio Preto, SP, Brazil
Contact: Raquel Hidalgo, MD    17997640004    draquelhidalgo@gmail.com   
Instituto de Assistência Médica ao Servidor Público Estadual de Sao Paulo Not yet recruiting
São Paulo, SP, Brazil
Contact: André Rezende, MD    +5511981359842    andrerezende@neurointervencao.com.br   
Universidade Federal de São Paulo - UNIFESP/EPM Not yet recruiting
São Paulo, SP, Brazil
Contact: Gisele S Silva, PhD       giselesampaio@hotmail.com   
Sponsors and Collaborators
Hospital de Clinicas de Porto Alegre
Hospital das Clínicas de Ribeirão Preto
Hospital Geral de Fortaleza
Hospital de Base
Federal University of São Paulo
Fundação Faculdade Regional de Medicina de São José do Rio Preto
UPECLIN HC FM Botucatu Unesp
University of Campinas, Brazil
Irmandade Santa Casa de Misericórdia de Porto Alegre
Universidade Federal do Paraná
Hospital Estadual Central
Hospital Sao Jose do Avai
Irmandade da Santa Casa de Misericordia de Sao Paulo
Federal University of Uberlandia
Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo
Investigators
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Principal Investigator: Raul G Nogueira, MD Emory University
Principal Investigator: Sheila CO Martins, MD, PhD Hospital de Clinicas de Porto Alegre
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Responsible Party: SHEILA CRISTINA OURIQUES MARTINS, Principal Investigator, Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier: NCT04256096    
Other Study ID Numbers: 17877519.6.1001.5327
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: February 10, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Because of the sensitive nature of the data collected for this study, requests to access the dataset from qualified researchers trained in human subject confidentiality protocols may be sent to the principal investigators
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: after de publication for 6 months
Access Criteria: Because of the sensitive nature of the data collected for this study, requests to access the dataset from qualified researchers trained in human subject confidentiality protocols may be sent to the principal investigators

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SHEILA CRISTINA OURIQUES MARTINS, Hospital de Clinicas de Porto Alegre:
stroke
ischemic stroke
thrombectomy
treatment
acute stroke
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes