EndoVascular Treatment With Stent-retriever and/or Thromboaspiration vs. Best Medical Therapy in Acute Ischemic Stroke

NCT ID: NCT02216643

Last Updated: 2020-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 221 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-08
• Study Completion Date: 2019-06-30

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.

Conditions

Stroke; Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

thrombectomy

mechanical thrombectomy with stentriever Solitaire FR® and/or thromboaspiration with Penumbra System® in patients with large vessel occlusion in cerebral anterior circulation vessels

Group Type: EXPERIMENTAL

Thrombectomy

Intervention Type: PROCEDURE

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.

Stentriever Solitaire FR® or Penumbra System®

Intervention Type: DEVICE

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.

best medical treatment

best medical treatment in patients with acute ischemic stroke with anterior circulation large vessel occlusion

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Thrombectomy

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.

Intervention Type: PROCEDURE

Stentriever Solitaire FR® or Penumbra System®

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.

Intervention Type: DEVICE

Other Intervention Names

Endovascular treatment; Intrarterial treatment; Endovascular revascularization

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Brazil

OTHER_GOV

Sponsor Role: collaborator

Medtronic

INDUSTRY

Sponsor Role: collaborator

Penumbra Inc.

INDUSTRY

Sponsor Role: collaborator

iSchemaView, Inc

UNKNOWN

Sponsor Role: collaborator

Brainomix Limited

INDUSTRY

Sponsor Role: collaborator

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

SHEILA CRISTINA OURIQUES MARTINS

MD, PHD, Stroke Neurologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raul Nogueira, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Sheila CO Martins, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Clínicas de Porto Alegre

Locations

Hospital Geral de Fortaleza/SUS

Fortaleza, Ceará, Brazil

Hospital Estadual Central

Vitória, Espírito Santo, Brazil

Hospital Geral Roberto Santos

Salvador, Estado de Bahia, Brazil

Hospital de Base do Distrito Federal

Brasília, Federal District, Brazil

Hospital de Clínicas da Universidade Federal do Paraná

Curitiba, Paraná, Brazil

Hospital São José do Avaí

Itaperuna, Rio de Janeiro, Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

UNIÃO BRASILEIRA DE EDUCAÇÃO E ASSISTENCIA, Hospital São Lucas PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Governador Celso Ramos

Florianópolis, Santa Catarina, Brazil

Clinica Neurologica e Neurocirurgica de Joinville S/S Ltda

Joinville, Santa Catarina, Brazil

Hospital das Clínicas da Faculdade de Medicina de Botucatu

Botucatu, São Paulo, Brazil

Hospital de Clínicas - UNICAMP

Campinas, São Paulo, Brazil

Hospital de Clínicas de Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

Irmandade da Santa Casa de Misericórdia

São Paulo, São Paulo, Brazil

Universidade Federal de São Paulo - UNIFESP/EPM

São Paulo, , Brazil

Countries

Brazil

References

Silva GS, Alves MM, Barros FCD, Frudit ME, Pontes-Neto OM, Mont'Alverne FJ, Rebello LC, Carbonera LA, Abud DG, Lima F, de Souza AC, Liebeskind D, Mosmann G, Bezerra D, Saver J, Cardoso F, Nogueira RG, Martins SO. The role of intravenous thrombolysis before mechanical Thrombectomy: A subgroup analysis of the RESILIENT trial. J Neurol Sci. 2024 Feb 15;457:122853. doi: 10.1016/j.jns.2023.122853. Epub 2023 Dec 20.

Reference Type: DERIVED

PMID: 38182456 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32521133 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30758449 (View on PubMed)

Other Identifiers

22042613.6.1001.5327

Identifier Type: -

Identifier Source: org_study_id