Clinical trial NCT04256096: Randomization of Endovascular Treatment in Acute Ischemic Stroke in the Extended Time Window
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Stroke, Ischemic
Keywords: stroke
ischemic stroke
thrombectomy
treatment
acute stroke
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
Collaborators: name: Hospital das Clínicas de Ribeirão Preto
name: Hospital Geral de Fortaleza
name: Hospital de Base
name: Federal University of São Paulo
name: Fundação Faculdade Regional de Medicina de São José do Rio Preto
name: UPECLIN HC FM Botucatu Unesp
name: University of Campinas, Brazil
name: Irmandade Santa Casa de Misericórdia de Porto Alegre
name: Universidade Federal do Paraná
name: Hospital Estadual Central
name: Hospital Sao Jose do Avai
name: Irmandade da Santa Casa de Misericordia de Sao Paulo
name: Federal University of Uberlandia
name: Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo
First posted: 2020-02-05
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The randomization employs a 1:1 ratio of mechanical thrombectomy with stent-retriever and/or thromboaspiration versus medical management alone
Primary purpose: TREATMENT

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

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.

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 ≤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).

Primary outcomes:
measure: Modified Rankin Scale scores
timeFrame: 90 days
Secondary outcomes:
measure: Proportion of Patients with Functional independence in 90 days
timeFrame: 90 days
measure: Disability on the utility-weighted modified Rankin scale (UW-mRS)
timeFrame: 90 days
measure: Quality of life measured by EuroQol Group 5-Dimension Self-Report Questionnaire (EuroQol / EQ5D)
timeFrame: 90 days and 1 year
measure: Mortality at 90 days
timeFrame: 90 days
measure: Proportion of patients with Intracranial Hemorrhage at 24 hours
timeFrame: 24 hours
measure: Procedural related complications
timeFrame: immediately after procedure
Other outcomes:
Locations:
city: Fortaleza
country: Brazil
facility: Hospital Geral de Fortaleza
state: Ceara
city: Brasília
country: Brazil
facility: Hospital de Base
state: DF
city: Vitória
country: Brazil
facility: Associacao Congregacao de Santa Catarina
state: Espirito Santo
city: Uberlândia
country: Brazil
facility: Hospital das Clínicas de Uberlândia
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital de Clínicas da Universidade Federal do Paraná
state: Parana
city: Itaperuna
country: Brazil
facility: Conferencia Sao jose do Avai
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RS
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre - ISCMPA
state: RS
city: Botucatu
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Botucatu
state: SP
city: Campinas
country: Brazil
facility: Hospital de Clínicas - UNICAMP
state: SP
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clinicas de Ribeirao Preto
state: SP
city: São José Do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina S J Rio Preto
state: SP
city: São Paulo
country: Brazil
facility: Instituto de Assistência Médica ao Servidor Público Estadual de Sao Paulo
state: SP
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo - UNIFESP/EPM
state: SP
Study officials:
affiliation: Emory University
name: Raul G Nogueira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Clinicas de Porto Alegre
name: Sheila CO Martins, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.