Clinical trial NCT02216643: EndoVascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Stroke
Ischemic Stroke
Keywords: Stroke
Ischemic Stroke
Thrombectomy
Reperfusion Therapy
Treatment
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Brazil
name: Medtronic
name: Penumbra Inc.
name: iSchemaView, Inc
name: Brainomix Limited
First posted: 2014-08-15
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Prospective, multi-center, randomized, controlled, open, blinded-endpoint trial with a sequential design. The randomization employs a 1:1 ratio of mechanical thrombectomy with stentriever and/or Thromboaspiration versus medical management alone. Randomization will be done under a minimization process using age, baseline NIHSS, use of IV tpa, vessel occlusion site and hospital. To evaluate the hypothesis that mechanical thrombectomy is superior to medical management alone in achieving more favorable outcomes in the distribution of the modified Rankin Scale scores at 90 days in subjects presenting with acute large vessel ischemic stroke \<8 hours from symptom onset. Subjects are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization. Sample size is projected to be 690 patients for a difference in treatment effect of 10%.

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.

Eligibility 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 ≤ 1)
3. Baseline NIHSS score obtained prior to randomization must be equal or higher than 8 points
4. Age ≥18 years
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. 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.
7. Informed consent obtained from patient or acceptable patient surrogate

Exclusion 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 or \> 400mg/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 (NIHSS item of consciousness \>1) (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 lactating 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 ≤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.)
14. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas).
15. 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.
16. Collaterals with malignant profile on CTA (without colateral circulation on CTA)
17. CT or MR evidence of hemorrhage (the presence of GRE microbleeds is allowed).
18. Significant mass effect with midline shift.
19. 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
20. Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation)
21. Evidence of intracranial tumor (except small meningioma).

Primary outcomes:
measure: Distribution of the modified Rankin Scale scores (shift analysis)
timeFrame: 90 days
Secondary outcomes:
measure: Functional independence (modified Rankin Score ≤ 2)
timeFrame: 90 days
measure: Infarct Burden at 24 hours
timeFrame: 24 hours
measure: Dramatic early favorable response
timeFrame: 24 hours
measure: Cost effectiveness
timeFrame: Life-time horizon perspective
measure: Quality of life analysis
timeFrame: 3 months, 6 months, 1 year
measure: Vessel recanalization at 24 hours
timeFrame: 24 hours
measure: Successful recanalization at the end of procedure
timeFrame: immediatelly after procedure (only thrombectomy arm)
measure: Mortality
timeFrame: 90 days
measure: Symptomatic Intracranial hemorrhage
timeFrame: 24 hours
measure: Procedure related complications
timeFrame: During the procedure
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Hospital Geral Roberto Santos
state: Bahia
city: Fortaleza
country: Brazil
facility: Hospital Geral de Fortaleza/SUS
state: Ceará
city: Brasília
country: Brazil
facility: Hospital de Base do Distrito Federal
state: DF
city: Vitória
country: Brazil
facility: Hospital Estadual Central
state: Espírito Santo
city: Curitiba
country: Brazil
facility: Hospital de Clínicas da Universidade Federal do Paraná
state: Paraná
city: Itaperuna
country: Brazil
facility: Hospital São José do Avaí
state: Rio De Janeiro
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: UNIÃO BRASILEIRA DE EDUCAÇÃO E ASSISTENCIA, Hospital São Lucas PUCRS
state: Rio Grande Do Sul
city: Joinville
country: Brazil
facility: Clinica Neurologica e Neurocirurgica de Joinville S/S Ltda
state: Santa Catarina
city: Florianópolis
country: Brazil
facility: Hospital Governador Celso Ramos
state: SC
city: São Paulo
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia
state: SP
city: Botucatu
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Botucatu
state: São Paulo
city: Campinas
country: Brazil
facility: Hospital de Clínicas - UNICAMP
state: São Paulo
city: Ribeirão Preto
country: Brazil
facility: Hospital de Clínicas de Ribeirão Preto
state: São Paulo
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo - UNIFESP/EPM
Study officials:
affiliation: Emory University
name: Raul Nogueira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Clínicas de Porto Alegre
name: Sheila CO Martins, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.