Combined Thrombectomy for Distal MediUm Vessel Occlusion StroKe

Официальное название

A Phase III, Randomized, Multicenter, Investigational, Open Label Clinical Trial That Will Examine Whether Treatment With Endovascular Thrombectomy is Superior to Standard Medical Therapy Alone in Patients Who Suffer a Distal Medium Vessel Occlusion Ischemic Strokes.

Обзор

A phase III, randomized, multi-center, investigational, open label clinical trial that will examine whether treatment with endovascular thrombectomy is superior to standard medical therapy alone in patients who suffer a Distal Medium Vessel Occlusion Ischemic Stroke within 12 hours from time last seen well

Подробное описание

DUSK is a Phase-3, prospective, multicenter, investigational, randomized, controlled, open-label study with blinded endpoint evaluation (PROBE design) and an adaptive design with population enrichment. The randomization employs a 1:1 ratio of endovascular thrombectomy (EVT) versus standard medical management (SMM) in patients who suffer a distal medium vessel occlusion (DMVO) stroke within 12 hours from time last seen well (TLSW) and have evidence of salvageable brain tissue on perfusion imaging. Randomization will be done under a minimization process using age (≤67 vs. \>67 years), baseline NIHSS (≤12 vs. \>12), use of IV thrombolysis (none vs. within 120 minutes from randomization vs. \> 120 minutes from randomization), site of occlusion (M2 vs. M3 vs. ACA vs. PCA), baseline infarct volume (≤15mL vs. \>15-30mL vs. \>30-50mL), perfusion mismatch volume (≤15mL vs. \>15-30mL vs. \>30-50mL), therapeutic window (0-4.5 vs. 4.5-8 or \>9-12 hours after TLKW), and participating site. The candidate enriched populations that the trial considers are based on use of intravenous thrombolysis (none vs. within 120 minutes from randomization vs. \> 120 minutes from randomization), TLKW to randomization (0-6 vs. 6-12 hours) and mismatch volumes as measured using absolute mismatch (defined as Tmax\>6 sec - DWI lesion on MRI or Tmax\>6 sec -rCBF\<30% lesion on CTP) (\>40 cc vs. \>30cc vs. \>20cc vs. \>10cc). The primary endpoint will be a categorical shift across all levels on the modified Rankin Scale (mRS) at 90-days post-randomization. The hypothesis is that EVT will lead to an improved clinical outcome at 90 days. Interim analysis will be performed after the primary endpoint is available for a total of 386 randomized patients.

Вмешательства

• Устройство Experimental: endovascular thrombectomy in patients who suffer a distal medium vessel occlusion
  The AXS Catalyst Distal Access Catheter is indicated for use in facilitating the insertion and guidance of appropriately sized interventional devices into a selected blood vessel in the peripheral and neurovascular systems, and is also indicated for use as a conduit for retrieval devices. The AXS Vecta Intermediate Catheter, as part of the AXS Vecta Aspiration System, is indicated in the revascularization of patients with acute ischemic stroke. Patients who are ineligible for intravenous tissue
• Другое Standard medical management
  All subjects should receive the best standard medical therapy based on current AHA guidelines. Subjects randomized to standard medical management (SMM) will receive standard medical therapy only based on the guidelines. All subjects are expected to be admitted to hospital as part of routine best guideline-based care and treated on a stroke unit or neurointensive care unit or equivalent.

Первичные конечные точки

• Shift in distribution of all levels of the 90-day modified Rankin Scale with levels 5-6 combined (mRS; 0, 1, 2, 3, 4, 5-6) as assessed by structured assessment [Срок оценки: 90-day follow-up]

Вторичные конечные точки (12)

• Shift in distribution of the 90-day mRS (0;1;2;3;4;5;6) as assessed by structured assessment [Срок оценки: 90-day follow-up]
• Rates of Independent Outcome defined as mRS ≤2 and/ or equal to Baseline mRS at 90 days [Срок оценки: 90-day follow-up]
• Rates of Excellent Outcome defined as mRS ≤1 and/ or equal to Baseline mRS at 90 days [Срок оценки: 90-day follow-up]
• Rates of Good Functional Outcomes adjusted for the baseline mRS and stroke severity (NIHSS) according to the modified Rankin Scale scores at 90 days as following: [Срок оценки: 90-day follow-up]
• EVT arm only: Final reperfusion grades according to the extended Thrombolysis in Cerebral Infarction (eTICI) scale and the rates of First Pass Effect (eTICI ≥2c) and Modified First Pass Effect (eTICI ≥2b50) [Срок оценки: 90-day follow-up]
• EVT arm only: Final reperfusion grades according to the rates of First Pass Effect (eTICI ≥2c) [Срок оценки: 90-Day follow up]
• EVT arm only: Final reperfusion grades according to the Modified First Pass Effect (eTICI ≥2b50) [Срок оценки: 90 day follow up]
• Mean score for disability on the utility-weighted modified Rankin scale (UW-mRS) at 90 days [Срок оценки: 90-day follow-up]
• Final infarct volume (FIV) (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 24 hours (-2/+12 hours) [Срок оценки: 24 hours (-2hours /+12 hours)]
• Final infarct growth (FIV - baseline infarct on CTP or DWI) [Срок оценки: 24 hours (-2 hours/+12 hours)]
• Final infarct volume (FIV) and infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 3-5 days (if available) [Срок оценки: 3-5 days]
• Final infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 3-5 days (if available) [Срок оценки: 3 to 5 days]

Критерии участия

Критерии включения

• Age ≥18 years (no upper age limit)
• Acute ischemic stroke where patient is ineligible for or has failed\* IV thrombolytic treatment and is ineligible for endovascular treatment under best guideline-based care due to absence of proximal arterial occlusion (e.g. intracranial ICA, MCA-M1 and co-dominant or dominant M2\*\* segments, and vertebrobasilar arteries).\*\*\*

\* IV thrombolytic treatment failure is defined by persistent disabling neurological deficits beyond 60 minutes of completion of thrombolytic infusion in the presence of imaging findings consistent with DMVO.

\*\*Dominant M2 segment is defined is a division supplying >50% of the MCA territory vs co-dominant supplying 50% of the MCA territory vs non-dominant supplying <50% of the MCA territory.

\*\*\*No procedures or tests required by the protocol will delay fastest possible delivery of thrombolytic therapy to potentially eligible subjects.

• Evidence of a primary (e.g. not secondary to EVT of proximal vessel occlusion) distal medium vascular occlusion defined as occlusion of the non-dominant M2 segment or M3 segment of the MCA, the ACA (A1, A2, or A3 segments), or the PCA (P1, P2 or P3 segments) resulting in significant clinical deficits and expected to be treatable by endovascular thrombectomy. Regardless of vessel anatomic location, all vessel diameters should be within 1.5mm -2.5mm. (refer to the device labeling for recommended vessel diameters for each device model.)\*
• No significant pre-stroke functional disability (mRS ≤2)
• Evidence of a disabling stroke defined as follows:

• Baseline National Institutes of Health Stroke Scale (NIHSS) score >5 at the time of randomization.
• NIHSS 3-5 with disabling deficit including significant aphasia, neglect, hemianopsia, or hemiparesis/ loss of hand or leg function as established by the treating team in context of the patient's life.
• The presence of a Target Mismatch defined as:

• Ischemic Core < 50cc (defined on NCCT/CTP\* or DWI-MRI)

\*Visual or automatedly detected hypodensity on NCCT should be used to exclude or include patients if the investigator believes that their assessment is more reliable than the CTP volume in any particular case.

• Mismatch Volume (TMax >6sec lesion - Core volume lesion) >10cc
• Mismatch Ratio >1.4
• Patient treatable within 12 hours of symptom onset. Symptoms onset is defined as the point in time the patient was last seen well (at baseline). Treatment start is defined as the time of arterial puncture.
• Informed consent obtained from patient or acceptable patient surrogate

Критерии исключения

• Any sign of intracranial hemorrhage on baseline CT/MR (SDH/SAH/ICH).
• Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in the patient having no residual disabling deficits and an NIHSS score of <5 at randomization.
• Significant ischemic changes in a territory other than the occluded site that in the opinion of the investigator could reduce the benefit of endovascular treatment.
• Contra indication to imaging with MR or CT with contrast agents.
• Infarct core >1/3 occluded territory (MCA, ACA, or PCA) qualitatively or >50 mL quantitatively (determined by NCCT, CTP or DWI).
• Any terminal illness such that patient would not be expected to survive more than 1 year.
• Recent past history or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm other than meningioma.
• Any imaging findings suggestive of futile recanalization in the judgment of the local investigator.
• Premorbid disability (mRS ≥3).
• Inability to initiate endovascular treatment within 12 hours of last seen well.
• Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS.
• Baseline blood glucose of <50 mg/dL (2.78 mmol) or >400 mg/dL (22.20 mmol).
• Known history of hereditary or acquired hemorrhagic diathesis and/or platelet count <100,000/uL.
• Known renal failure as defined as serum creatinine levels > 3.0 mg/dL.
• Presumed septic embolus or suspicion of bacterial endocarditis.
• Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the subject if an endovascular procedure was performed.
• History of drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Subjects with occlusions in multiple vascular territories (e.g., bilateral or multi-territorial anterior circulation, or anterior/posterior circulation)
• Subject participating in a study involving an investigational drug or device that would impact this study
• Known pregnancy
• Prisoner or incarceration
• Known acute symptomatic COVID-19 infection

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Grady Health System — Atlanta
• UI Health Care Medical Center — Iowa City
• ProMedica — Toledo
• University of Pittsburgh — Pittsburgh

Публикации

• Ospel JM, Goyal M. A review of endovascular treatment for medium vessel occlusion stroke. J Neurointerv Surg. 2021 Jul;13(7):623-630. doi: 10.1136/neurintsurg-2021-017321. Epub 2021 Feb 26. PMID 33637570
• Saver JL, Chapot R, Agid R, Hassan A, Jadhav AP, Liebeskind DS, Lobotesis K, Meila D, Meyer L, Raphaeli G, Gupta R; Distal Thrombectomy Summit Group*dagger. Thrombectomy for Distal, Medium Vessel Occlusions: A Consensus Statement on Present Knowledge and Promising Directions. Stroke. 2020 Sep;51(9):2872-2884. doi: 10.1161/STROKEAHA.120.028956. Epub 2020 Aug 6. No abstract available. PMID 32757757
• Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guid PMID 31662037
• Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, Schellinger PD, Toni D, de Vries J, White P, Fiehler J. European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischaemic StrokeEndorsed by Stroke Alliance for Europe (SAFE). Eur Stroke J. 2019 Mar;4(1):6-12. doi: 10.1177/2396987319832140. PMID 31165090
• Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, Levi CR, Hsu C, Kleinig TJ, Fatar M, Leys D, Molina C, Wijeratne T, Curtze S, Dewey HM, Barber PA, Butcher KS, De Silva DA, Bladin CF, Yassi N, Pfaff JAR, Sharma G, Bivard A, Desmond PM, Schwab S, Schellinger PD, Yan B, Mitchell PJ, Serena J, Toni D, Thijs V, Hacke W, Davis SM, Donnan GA; EXTEND, ECASS-4, and EPITHET Investigators PMID 31128925
• Ospel JM, Menon BK, Demchuk AM, Almekhlafi MA, Kashani N, Mayank A, Fainardi E, Rubiera M, Khaw A, Shankar JJ, Dowlatshahi D, Puig J, Sohn SI, Ahn SH, Poppe A, Calleja A, Hill MD, Goyal M. Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment. Stroke. 2020 Nov;51(11):3232-3240. doi: 10.1161/STROKEAHA.120.030227. Epub 2020 Oct 19. PMID 33070714
• Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborator PMID 26898852
• Menon BK, Hill MD, Davalos A, Roos YBWEM, Campbell BCV, Dippel DWJ, Guillemin F, Saver JL, van der Lugt A, Demchuk AM, Muir K, Brown S, Jovin T, Mitchell P, White P, Bracard S, Goyal M. Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration. J Neurointerv Surg. 2019 Nov;11(11):1065-1069. doi: 10.1136/ PMID 30975736

Идентификаторы

NCT: NCT05983757 · STUDY23030032

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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