- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02216643
EndoVascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke (RESILIENT)
Randomization of Endovascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke Due to Large VEssel OcclusioN Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients with acute ischemic stroke related to anterior circulation large vessel occlusion will be randomized up to 8 hours from symptoms onset in both arms (mechanical thrombectomy versus medical management alone). Subjects are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization. They will be admitted at acute stroke units in Brazil (or ICU if needed) and treated following international guidelines. Concomitant medications and non-pharmacological therapies will be recorded. A maximum of six attempts to retrieve the thrombus in a single vessel can be made. No additional treatment will be allowed either with Intrarterial tPA, mechanical devices or angioplasty/stenting.
The primary endpoint will be distribution of the modified Rankin Scale scores at 90 days (shift analysis) as evaluated by two separate assessors who are blinded to treatment
Interim Analysis The sample size for this Phase III Trial is projected to be 690 subjects. For interim analyses, the method of Lan and DeMets will be used to allocate alpha via the power family method with φ (phi) equal to 1 for the assessment of efficacy and futility, respectively after the first 174, 346 and 518 patients enrolled have completed the 90-day follow-up. The interval may be more frequent if requested by the Data and Safety Monitoring Board (DSMB). At interim analysis, in case the stopping boundaries are crossed the DSMB may recommend stopping the study either for better efficacy of the tested treatment either for futility. Other factors, such as safety, will be taken into consideration by the DSMB in the decision to stop the study. When considering stopping the trial for safety reasons, the DSMB will be instructed to consider both mortality (mRS=6) and severe dependency (mRS=5) at 3 months as one single outcome.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
São Paulo, Brazil
- Universidade Federal de Sao Paulo - UNIFESP/EPM
-
-
Bahia
-
Salvador, Bahia, Brazil
- Hospital Geral Roberto Santos
-
-
Ceará
-
Fortaleza, Ceará, Brazil
- Hospital Geral de Fortaleza/SUS
-
-
DF
-
Brasília, DF, Brazil
- Hospital de Base do Distrito Federal
-
-
Espírito Santo
-
Vitória, Espírito Santo, Brazil
- Hospital Estadual Central
-
-
Paraná
-
Curitiba, Paraná, Brazil
- Hospital de Clínicas da Universidade Federal do Paraná
-
-
Rio De Janeiro
-
Itaperuna, Rio De Janeiro, Brazil
- Hospital São José do Avaí
-
-
Rio Grande Do Sul
-
Porto Alegre, Rio Grande Do Sul, Brazil, 90035903
- Hospital de Clinicas de Porto Alegre
-
Porto Alegre, Rio Grande Do Sul, Brazil
- UNIÃO BRASILEIRA DE EDUCAÇÃO E ASSISTENCIA, Hospital São Lucas PUCRS
-
-
SC
-
Florianópolis, SC, Brazil
- Hospital Governador Celso Ramos
-
-
SP
-
São Paulo, SP, Brazil
- Irmandade da Santa Casa de Misericórdia
-
-
Santa Catarina
-
Joinville, Santa Catarina, Brazil
- Clinica Neurologica e Neurocirurgica de Joinville S/S Ltda
-
-
São Paulo
-
Botucatu, São Paulo, Brazil
- Hospital das Clínicas da Faculdade de Medicina de Botucatu
-
Campinas, São Paulo, Brazil
- Hospital de Clínicas - UNICAMP
-
Ribeirão Preto, São Paulo, Brazil
- Hospital de Clínicas de Ribeirão Preto
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- No significant pre-stroke functional disability (mRS ≤ 1)
- Baseline NIHSS score obtained prior to randomization must be equal or higher than 8 points
- Age ≥18 years
- 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.
- Patient treatable within eight 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 groin puncture.
- Informed consent obtained from patient or acceptable patient surrogate
Exclusion Criteria:
- Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 3.0
- Baseline platelet count < 30.000/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 beyond 4,5 hours from the beginning of the symptoms
- Woman of childbearing potential who is known to be pregnant or lactating 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
- Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤1. 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.)
- Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas).
- Hypodensity on CT or restricted diffusion amounting to an ASPECTS score of <6 on NCCT, or <5 on DWI MRI. The use of CTP or MRI perfusion is optional.
- Collaterals with malignant profile on CTA (without colateral circulation on CTA)
- CT or MR evidence of hemorrhage (the presence of GRE 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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: thrombectomy
mechanical thrombectomy with stentriever Solitaire FR® and/or thromboaspiration with Penumbra System® in patients with large vessel occlusion in cerebral anterior circulation vessels
|
Patients with acute ischemic stroke with anterior circulation large vessel occlusion will be randomized to receive mechanical thrombectomy with stent-retriever Solitaire FR® and/or thromboaspiration with Penumbra System® versus medical management alone versus medical management alone.
A maximum of six attempts to retrieve the thrombus in a single vessel can be made .
No additional treatment will be allowed either with IA tPA, other mechanical devices or angioplasty/stenting.
Other Names:
Patients with acute ischemic stroke with anterior circulation large vessel occlusion will be randomized to receive mechanical thrombectomy with stent-retriever and/or thromboaspiration versus medical management alone versus medical management alone.
A maximum of six attempts to retrieve the thrombus in a single vessel can be made .
No additional treatment will be allowed either with IA tPA, other mechanical devices or angioplasty/stenting.
|
No Intervention: best medical treatment
best medical treatment in patients with acute ischemic stroke with anterior circulation large vessel occlusion
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Distribution of the modified Rankin Scale scores (shift analysis)
Time Frame: 90 days
|
Distribution of the modified Rankin Scale scores at 90 days (shift analysis) as evaluated by two separate assessors who are blinded to treatment
|
90 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Functional independence (modified Rankin Score ≤ 2)
Time Frame: 90 days
|
Functional independence measured by modified Rankin Score ≤ 2 in 90 days in both groups
|
90 days
|
Infarct Burden at 24 hours
Time Frame: 24 hours
|
ASPECTS change from baseline to 24 hours on CT or MRI
|
24 hours
|
Dramatic early favorable response
Time Frame: 24 hours
|
defined as an NIHSS score 0-2 or a NIHSS score decrease of ≥8 from baseline at 24 hours
|
24 hours
|
Cost effectiveness
Time Frame: Life-time horizon perspective
|
Cost effectiveness analysis of interventional therapy vs medical therapy alone
|
Life-time horizon perspective
|
Quality of life analysis
Time Frame: 3 months, 6 months, 1 year
|
Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year, between interventional therapy vs medical therapy alone
|
3 months, 6 months, 1 year
|
Vessel recanalization at 24 hours
Time Frame: 24 hours
|
Vessel recanalization evaluated by CT angiography (CTA) or MR angiography (MRA) at 24 hours in both treatment groups
|
24 hours
|
Successful recanalization at the end of procedure
Time Frame: immediatelly after procedure (only thrombectomy arm)
|
defined as a grade of 2b or 3 (indicating reperfusion of >50% of the affected territory) on the modified Thrombolysis in Cerebral Infarction (mTICI) scale
|
immediatelly after procedure (only thrombectomy arm)
|
Mortality
Time Frame: 90 days
|
Mortality at 90 days
|
90 days
|
Symptomatic Intracranial hemorrhage
Time Frame: 24 hours
|
Clinically significant Intracranial hemorrhage (ICH) rates at 24 (-2/+12) hours.
All intracerebral hemorrhages will be classified by a central core-lab using the ECASS criteria for CT evaluation.
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.
The incidence of any asymptomatic hemorrhage measured at 24 (-2/+12) hours will also be compared
|
24 hours
|
Procedure related complications
Time Frame: During the procedure
|
Complications occurring during the procedure will be evaluated: distal embolization in a new territory, arterial dissection, arterial perfuration, groin hematoma
|
During the procedure
|
Collaborators and Investigators
Investigators
- Principal Investigator: Raul Nogueira, MD, Emory University
- Principal Investigator: Sheila CO Martins, MD, Hospital de Clinicas de Porto Alegre
Publications and helpful links
General Publications
- Martins SO, Mont'Alverne F, Rebello LC, Abud DG, Silva GS, Lima FO, Parente BSM, Nakiri GS, Faria MB, Frudit ME, de Carvalho JJF, Waihrich E, Fiorot JA Jr, Cardoso FB, Hidalgo RCT, Zetola VF, Carvalho FM, de Souza AC, Dias FA, Bandeira D, Miranda Alves M, Wagner MB, Carbonera LA, Oliveira-Filho J, Bezerra DC, Liebeskind DS, Broderick J, Molina CA, Fogolin Passos JE, Saver JL, Pontes-Neto OM, Nogueira RG; RESILIENT Investigators. Thrombectomy for Stroke in the Public Health Care System of Brazil. N Engl J Med. 2020 Jun 11;382(24):2316-2326. doi: 10.1056/NEJMoa2000120.
- Gagliardi VDB, Gagliardi RJ. Current and future conditions of stroke care in Brazil. Arq Neuropsiquiatr. 2019 Jan;77(1):68-69. doi: 10.1590/0004-282X20180160. No abstract available.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 22042613.6.1001.5327
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Stroke
-
University Hospital, GhentRecruitingStroke | Stroke, Ischemic | Stroke, Acute | Stroke Sequelae | Stroke HemorrhagicBelgium
-
Moleac Pte Ltd.RecruitingStroke | Stroke, Ischemic | Stroke Sequelae | Stroke, Cardiovascular | Strokes Thrombotic | Stroke, Embolic | Stroke, CryptogenicSingapore, Philippines
-
Moleac Pte Ltd.Not yet recruitingStroke | Stroke, Ischemic | Stroke Sequelae | Stroke, Cardiovascular | Strokes Thrombotic | Stroke, Embolic | Stroke, Cryptogenic
-
IRCCS San Camillo, Venezia, ItalyRecruitingStroke | Stroke, Ischemic | Stroke Sequelae | Stroke HemorrhagicItaly
-
Vanderbilt University Medical CenterPatient-Centered Outcomes Research Institute; University of Alabama at BirminghamEnrolling by invitationStroke | Stroke, Ischemic | Stroke, Acute | Stroke Sequelae | Engagement, Patient | Stroke HemorrhagicUnited States
-
University of MinnesotaAmerican Occupational Therapy FoundationRecruitingStroke | Stroke Sequelae | Stroke Hemorrhagic | Stroke IschemicUnited States
-
University of British ColumbiaCanadian Institutes of Health Research (CIHR); Michael Smith Foundation for...RecruitingStroke | Stroke, Ischemic | Stroke Hemorrhagic | Chronic StrokeCanada
-
University of CincinnatiMedical University of South Carolina; University of California, Los Angeles; University...RecruitingStroke | Stroke, Ischemic | Stroke, Acute | Stroke HemorrhagicUnited States
-
University of LiegeCompletedStroke, Acute | Stroke Hemorrhagic | Stroke, ComplicationBelgium
-
Turkish Stroke Research and Clinical Trials NetworkElectroCore INC; Turkish Neurological SocietyCompletedStroke | Stroke, Ischemic | Stroke, Acute | Stroke, HemorrhagicTurkey
Clinical Trials on Thrombectomy
-
Paul J. GagneRecruitingAcute Deep Venous Thrombosis of Ileofemoral VeinUnited States
-
SurModics, Inc.RecruitingPeripheral Arterial Disease | Acute Limb IschemiaUnited States
-
Careggi HospitalCardiovascular Research Foundation, New YorkCompletedST-segment Elevation Myocardial Infarction | ThrombusItaly
-
Assiut UniversityRecruitingAcute Limb IschemiaEgypt
-
RapidPulse, IncNot yet recruiting
-
RapidPulse, IncNot yet recruitingStroke | Acute Ischemic Stroke | Large Vessel Occlusion | Mechanical ThrombectomyGeorgia
-
Hopital FochRecruiting
-
Reverse Medical CorporationSuspendedIschemic StrokeUnited States
-
Hopital FochRecruitingStroke, AcuteFrance
-
ThrombX MedicalNot yet recruitingIschemic Stroke