Table 5.

List of ongoing and upcoming trials aimed to address the issues concerning the endovascular treatment of acute ischemic stroke

Trial	Time window	Purpose	Inclusion criteria	Outcome measure
RACECAT [225]	0-8 h	Triage of the acute LVO on direct transfer to EVT-SC bypassing LSC vs. transfer to the LSC according to the current stroke protocol.	Premorbid mRS 0–2 Age ≥ 18 Suspected LVO AIS identified by a RACE scale score > 4 evaluated by EMS professional Time to arrival at EVT-SC <7 h from symptom onset	mRS at 90 days (shift analysis) Mortality at 90 days Mortality in haemorrhagic stroke patients Clinical deterioration (≥4 points on the NIHSS) Clinical benefit of direct vs. local transfer Dramatic early favourable response (NIHSS improvement ≥8 or NIHSS score of 0–2 at 24 h)
DEFUSE 3 [198]	6-16 h	Benefit of carefully selected patients with target mismatch and MCA (M1 segment) or ICA occlusion using CT/MR within 6–16 h treated with MT plus standard therapy vs. standard therapy alone.	Age 18–90 years Baseline NIHSSS is ≥6 Time to endovascular treatment since symptom onset = 6–16 h Premorbid mRS 0–2 ICA or MCA-M1 occlusion by MRA or CTA and target mismatch profile on CTP or MRI (ischemic core volume < 70 mL, mismatch ratio >/= 1.8, and mismatch volume >/= 15 mL) ASPECT on NCCT >/=6 No evidence of tumour, mass effect with midline shift, ICA or aortic dissection No occlusions in multiple vascular territories	Distribution of mRS scores at 90 days Proportion of patients with mRS 0–2 Infarct growth within 24 h Reperfusion rates at 24 h Ischemic lesion growth at 24 h
DAWN [119, 200]	6-24 h	MT using the Trevo Retriever with medical management is superior to medical management alone in improving clinical outcomes at 90 days in appropriately selected wake up and late presenting AIS within 6–24 h after symptom onset [119]	Subjects with failed IV-tPA or contraindicated for IV-tPA Age ≥ 18 Baseline NIHSS ≥ 10 Can be randomised within 6–24 h of stroke onset Pre-stroke mRS 0 or 1 <1/3 MCA territory involved, as evidenced by CT or MRI Intracranial ICA and/or MCA-M1 occlusion on MRA/CTA CIM defined on MR-DWI or CTP-rCBF maps: (a) 0- < 21 cm3 core infarct and NIHSS ≥10 (and age ≥ 80 years old), (b) 0- < 31 cm3 core infarct and NIHSS ≥10 (and age < 80 years old), or (c) 31 cm3to <51 cm3 core infarct and NIHSS ≥20 (and age < 80 years old) ICH or differential diagnosis on CT/MRI	Weighted mRS at 90 days Mortality at 90 days Good functional outcome (mRS 0–2) Revascularization rate at 24 h on CTA/MRA Neurological deterioration defined by as ≥4-point increase in the NIHSS score from the baseline score at 5–7 days or at discharge.
POSITIVE [199]	6-12 h	To determine the safety and efficacy of IAT in AIS patients Ineligible for or refractory to IV-rtPA as selected by physiologic imaging	Age ≥ 18 NIHSS ≥8 at the time of neuroimaging Time to the groin puncture 6–12 h Large vessel proximal occlusion (distal ICA through MCA M1 bifurcation) Patients who have had IV-tPA without improvement in symptoms Pre-stroke morbidity mRS 0–1 Presence of large penumbra No evidence of SAH or ICH or mass effect with midline shift <1/3 MCA territory involved, as evidenced by baseline CT or ASPECTS of >7	90 day mRS Good functional outcome mRS 0–2 at 90 days Mortality at 30 and 90 days ICH with neurological deterioration (NIHSS worsening >4) within 24 h Arterial revascularization measured by TICI 2b or 3 following MT
ENDOSTROKE [287]	NR	Predictors of the good or poor clinical outcome following MT in AIS	Age ≥ 18 years Proximal arterial vessel occlusion No evidence of venous occlusion	mRS at 90 days Complete recanalization defined by TIMI grade two or 3. Periprocedural complication rate (sICH defined by ECASS PH1 and PH2, SAH and thromboembolic events).
START [288]	0-8 h	Efficacy of the Penumbra System in AIS with a known core infarct volume at admission presenting within 8 h of onset. To study the correlation between infarct-volume and functional outcome at 90 days in MT treated patients	Age 18 to 85 years NIHSS ≥10 at admission Evidence of proximal large vessel occlusion (supra clinoid segment of ICA through the M1 segment of MCA) Patients presenting within 8 h, and those within 3 h must be ineligible or refractory to IV-rtPA Core infarct volume assessed by CTP, CTA or DWI scans within 60 min to arterial puncture. No history of stroke within 3 months No evidence of mass effect with midline shift or ICH on NCCT No evidence of arterial stenosis proximal to the occlusion that could prevent thrombectomy No evidence of preexisting arterial injury Life expectancy <90 days	Good functional outcome mRS 0–2 at 90 days Recanalization assessment using TIMI and mTICI immediately after MT Periprocedural serious events Good neurological recovery (NIHSS ≥10) at discharge Incidence of sICH and asymptomatic haemorrhage defined by ECASS criteria and patient neurological status within 24 h of the procedure.
EASI [289]	0-5 h	To evaluate the efficacy of IV-rtPA vs combined (MT plus IV-rtPA) treatment in AIS	Age ≥ 18 NIHSS ≥8 Onset to treatment less than 5 h or symptom/imaging mismatch Occlusion of MCA (m1 or M2), supraclinoid ICA or basilar trunk No evidence of haemorrhagic transformation of the infarcted territory	Favourable clinical outcome (mRS 0–2 at 90 days) sICH on CT at 24 h Infarct evolution on CT between pre-treatment and 24 h using the ASPECT score Recanalization using TICI scale after thrombectomy Procedural complication within 3 months ICH on NCCT at 24 h
BASICS [221, 222]	0-6 h	Efficacy and safety of IAT plus standard medical therapy vs. standard medical alone in patients with an acute symptomatic basilar artery occlusion (BAO)	Symptoms of BAO stroke BAO confirmed by CTA or MRA Age ≥ 18 NIHSS ≥8 at the time of neuroimaging IAT initiated within 6 h of onset of symptoms Premorbid score of 0–2 No ICH or mass effect on CT	Favourable outcome mRS 0–2 Excellent outcome mRS 0–3 Recanalization at 24 ± 6 h on CTA Volume of infarction on NCCT and CTA source images at 24 ± 6 h sICH at 24 ± 6 h on CTA Mortality at 90 days NIHSS pre, and port IV-tPA and at 24 h EQ-5D – Quality of life at 90 and 120 days
SIESTA [207, 213]	NR	Efficacy of conscious sedation vs. general anaesthesia during IAT. Update: No advantage for the use of conscious sedation recently reported [213].	Age ≥ 18 years Acute stroke in anterior circulation ICA or MCA occlusion on CTA No evidence of ICH	Higher NIHSS of >10 at 24 h NIHSS improvement mRS at 90 days Mortality before discharge or at 90 days Duration of hospital stay Recanalization status on TICI Periinterventional complications
GOLIATH [208]	NR	Efficacy of general vs. local anaesthesia during IAT	Age ≥ 18 years NIHSS > 10 mRS = <2 groin puncture < 6 h from stroke onset occlusion of ICA, ICA-T, M1, M2 GCS > 9 No evidence of posterior circulation stroke	Growth of DWI lesion (48–72 h] mRS score at 90 days Blood pressure during intervention (1–2 h) Time from arrival to the groin puncture and recanalization (1–2 h)
ANSTROKE [209]	NR	To study the efficacy of general anaesthesia vs sedation technique during embolectomy for AIS stroke (systolic pressure 140–180 mmHg)	Age ≥ 18 years CTA confirmed occlusion in ICA, ACA (A1 segment), MCA (M1 or M2 segments) NIHSS ≥14 for patients with embolus in left hemisphere or NIHSS ≥10 for embolus in right hemisphere No evidence of posterior circulation embolus No evidence of ICH on CT Pre-stroke mRS of ≤3 No evidence of spontaneous recanalization	90 day mRS Change in NIHSS score compared to admission (Day 3, 7 and 90) Degree of recanalization and reperfusion (1 day after embolectomy) Periprocedural complications Infarction magnitude CT day 1 including CTP MR on day 3 (2–4) and 3 months Brain markers (GFAP, Tau, S-100B) before, 2, 24, 48, 72 h and 3 months after the embolectomy Quantitative EEG 1, 2 and 90 days after onset Length of hospital stay Preprocedural time consumption (stroke onset to CTA, CTA to start of anaesthesia/ sedation, stroke onset to start of embolectomy and duration of embolectomy.
MOST [226]	NR	Phase III trial to explore the efficacy of IV delivery of antithrombotic medications Argatroban and Eptifibatide in combination with rtPA in AIS.	NIHSS > 6	mRS at 90 days longitudinal model relating 30 day mRS to 90 days mRS

RACECAT Direct Transfer to an Endovascular Centre Compared to Transfer to the Closest Stroke Centre in Acute Stroke Patients With Suspected Large Vessel Occlusion; RACE scale Rapid Arterial occlusion Evaluation; mRS Modified Rankin score; EMS Emergency medical service; LVO Large vessel occlusion; AIS Acute ischemic stroke; LSC Local stroke centre; EVT-LSC Endovascular stroke centre; DEFUSE-3 Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3; DAWN Trevo and Medical Management Versus Medical Management Alone in Wake Up and Late Presenting Strokes; BASICS Basilar Artery International Cooperation Study; IAT Intra-arterial therapy; IV-rtPA Intra venous tissue plasminogen activator; NCCT Non-contrast computed tomography; CTA CT angiography; sICH Symptomatic intracranial haemorrhage; SAH Sub-arachnoid haemorrhage; BAO Basilar artery occlusion; SIESTA Sedation vs. Intubation for Endovascular Stroke Treatment; GOLIATH The General or Local Anaesthesia in Intra-arterial Therapy; MOST The Multi-Arm Optimization of Stroke Thrombolysis; NR Not required; ANSTROKE Sedation Versus General Anaesthesia for Endovascular Therapy in Acute Stroke - Impact on Neurological Outcome; ENDOSTROKE International Multicenter Registry for Mechanical Recanalization Procedures in Acute Stroke; TIMI Thrombolysis in Myocardial Infarction; START Imaging Guided Patient Selection for Interventional Revascularization Therapy; EASI Endovascular Acute Stroke Intervention Trial