Clinical Research Directory

INTRA-ARTERIAL MeVO TREATMENT (IMP-ACT) Within the ACT-GLOBAL Adaptive Platform Trial-NCT06352632

This domain will be conducted as part of ACT-GLOBAL platform trial and will have the nested domain name of IMP-ACT. Acute ischemic stroke (AIS) caused by intracranial arterial occlusion remains a major cause of disability and death. Medium vessel occlusion stroke (MeVO), involving distal medium-sized intracranial arteries, accounts for approximately 25-40% of all AIS cases. Despite best medical management, including intravenous thrombolysis, up to 40% of MeVO patients fail to regain functional independence, and mortality remains approximately 10%. These poor outcomes prompted several randomized trials evaluating endovascular thrombectomy (EVT) for MeVO stroke, including the CIHR-funded ESCAPE-MeVO trial. ESCAPE-MeVO, DISTAL, and DISCOUNT did not demonstrate overall benefit of EVT compared with best medical management, whereas ORIENTAL-MeVO reported benefit in an Asian population. These conflicting findings have resulted in uncertainty regarding optimal MeVO management and suggest that treatment benefit may depend on patient selection. A potential explanation for the neutral EVT trials is suboptimal reperfusion. In ESCAPE-MeVO, successful reperfusion was achieved in only 75% of patients, leaving substantial room for procedural improvement. At the same time, major procedural complications were infrequent, supporting the feasibility of exploring strategies to enhance reperfusion. Subgroup analyses from ESCAPE-MeVO suggested that treatment effect may vary according to time from symptom onset and collateral status. Patients treated early after stroke onset and those with favorable collaterals appeared to derive greater benefit from EVT than later presenters or patients with poor collateral circulation. These findings support a more targeted treatment approach in selected MeVO patients. Intra-arterial thrombolysis (IAT) has emerged as a promising adjunct to EVT. Local delivery of thrombolytic agents may dissolve residual distal thrombi that are inaccessible or unsafe to treat mechanically and may improve both macrovascular and microvascular reperfusion. Because thrombus burden is generally smaller in MeVO stroke, adjunctive IAT may be particularly effective in this population. However, no randomized trial has evaluated combined EVT and IAT for primary MeVO stroke. This study will address that evidence gap and determine whether adjunctive IAT can improve outcomes in carefully selected patients with MeVO stroke.

Intra-arterial Thrombolysis For Acute Ischemic Stroke With Medium Vessel Occlusion

A multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) phase III trial is planned to evaluate the efficacy and safety of intra-arterial thrombolysis (IAT) in patients with acute ischemic stroke caused by medium vessel occlusion (MeVO, distal M2 \[above the mid-insular height\], M3 or M4; A2, A3 or A4; or P2 or P3 segments, confirmed by CTA or MRA), compared with best medical management alone. Eligible participants (aged 18-80 years, baseline NIHSS score 6-25, confirmed MeVO within 24 hours of symptom onset or last known well) will be randomly assigned 1:1 to the intra-arterial thrombolysis plus best medical management group or the best medical management alone group. The primary endpoints are (i) the proportion of patients with a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-2 at 90±7 days post-randomization; (ii) the proportion of patients with symptomatic intracranial hemorrhage (sICH) within 48 hours post-randomization, defined and classified according to the Heidelberg Bleeding Classification; and (iii) the proportion of patients with early neurological deterioration (END) within 7 days post-randomization, defined as an increase of ≥ 4 points in the total NIHSS score from baseline or an increase of ≥ 2 points in any single NIHSS item. Secondary endpoints: 1. Procedure-related complications within 24 hours post-randomization; 2. Recanalization rate (meTICI ≥ 2b) at 24±12 hours post-randomization; 3. Any intracranial hemorrhage within 48 hours post-randomization; 4. Early neurological improvement (NIHSS score change from baseline) at 7 days or discharge; 5. Overall distribution of mRS scores at 90±7 days (shift analysis); 6. Excellent functional outcome (mRS score 0-1) at 90±7 days; 7. Functional independence (Barthel Index score 95 or 100) at 90±7 days; 8. Health-related quality of life (EQ-5D-5L) at 90±7 days; 9. All-cause mortality within 90±7 days.

PROMISE Registry: PROspective Study on Management of Ischemic Stroke Secondary to mEvo Registry

Investigators are conducting a real world, observational, prospective, multicenter study to better understand treatment for patients with MeVo and distal vessel occlusions in the U.S post publication of recent MeVO trials.

Intra-arterial Tenecteplase for Acute Medium Vessel Occlusion Stroke

The ANGEL-MeVO-TNK is a multicentered, prospective, randomized, open label, blinded endpoint (PROBE) phase III trial. A total of 488 AIS patients (age ≥18 years) with acute MeVO-AIS (occlusion of the M2/M3, the A1/A2/A3, the P1/P2/P3, and with baseline NIHSS score \>5 or disabling stroke with NIHSS score 3-5 \[such as neurological deficits in motor strength, language, vision, etc\]), will be enrolled. Patients fulfilling all the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into the IA TNK group or the control group after offering informed content. * The IA TNK group：1) If the patient has not received IVT, IA TNK will be administered as a slow, continuous infusion for super-selective contact thrombolysis in a stepwise manner: an initial dose of 0.0625 mg/kg with a duration of 15 minutes. A repeat angiographic assessment will then be performed; if recanalization is not achieved, an additional dose of 0.0625 mg/kg will be administered over a further 15 minutes (maximum dose 12.5 mg) . 2\) If the patient has received IVT, intra-arterial TNK will be administered as a slow infusion for super-selective contact thrombolysis at a dose of 0.0625 mg/kg (maximum dose 6.25 mg) with a duration of 15 minutes. * The control group will be given standard medical management. The study consists of four visits including the day of randomization, 48±12 hours after randomization, and 90±7 days after randomization. Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment neurological function rating scale will be recorded during the program. The primary outcome is the modified Rankin Scale (mRS) score of 0 to 1 at 90±7 days after onset. The primary safety outcome is the incidence of sICH within 48±12 hours after randomization (ECASS III).

Intra-arterial Thrombolysis for Acute Ischemic Stroke With Medium Vessel Occlusion

Acute ischemic stroke (AIS) due to medium vessel occlusion (MeVO) or severe stenosis poses a significant clinical challenge. Recent large randomized controlled trials, DISTAL and ESCAPE-MeVO, demonstrated no significant benefit of endovascular therapy in patients with MeVO. Although intra-arterial thrombolysis has shown promise in clinical experience, robust evidence supporting its efficacy in MeVO or severe stenosis-related AIS is still absent. To fill this gap, the RESCUE MeVO trial has been designed as a multicenter, prospective, randomized, open-label, blinded end-point (PROBE) study to evaluate the efficacy and safety of intra-arterial thrombolysis in patients with AIS caused by MeVO or severe stenosis.

Intra-arterial Recombinant Human Tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Medium Vessel Occlusion

Medium vessel occlusion (MeVO) accounts for 20-45% of acute ischemic stroke (AIS). Although patients with MeVO often present with relatively low NIHSS scores, up to one-third remain functionally dependent at follow-up despite receiving standard medical therapy, including intravenous thrombolysis. Recent randomized trials (DISTAL, ESCAPE-MeVO, DISCOUNT) have not demonstrated clinical benefit of endovascular treatment (EVT) for MeVO and have suggested higher risks of symptomatic intracranial hemorrhage and mortality, underscoring the need for safer and more targeted reperfusion strategies. Intra-arterial thrombolysis (IAT) enables localized, high-concentration thrombolytic delivery with minimal mechanical manipulation, which may be advantageous for medium and distal vessels. Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA), a genetically engineered third-generation thrombolytic agent, has shown favorable pharmacologic properties and clinical safety in AIS, including in intra-arterial use following EVT. However, prospective evidence supporting its direct therapeutic role in MeVO-related AIS remains lacking. This multicenter, prospective, open-label randomized controlled trial with blinded endpoint assessment is designed to evaluate the efficacy and safety of intra-arterial rhTNK-tPA thrombolysis in improving functional outcome in MeVO within 24 hours of symptom onset.