Intra-Arterial Thrombolysis After SUCCESSful Reperfusion in Anterior Circulation Ischemic Stroke (IA-SUCCESS)

Intra-Arterial Thrombolysis After SUCCESSful Angiographic Recanalization in Acute Large Vessel Occlusion Stroke of the Anterior Circulation: the IA-SUCCESS Multicenter, Randomized Clinical Trial

Stroke is a leading cause of disability and mortality worldwide. Despite the clinical benefit of mechanical thrombectomy, 1 out of 2 patients treated are functionally independent at 90 days. Achieving the best possible angiographic reperfusion is a key determinant of clinical outcome in acute ischemic stroke patients with anterior circulation large vessel occlusion. Mechanical thrombectomy is standard treatment for large vessel occlusion stroke patients within 24. In the setting of successful (eTICI ≥2b), adjunct intra-arterial thrombolysis may be a promising therapeutic option allowing recanalization of distal arterial occlusions (not accessible to mechanical devices) and improvement of upstream brain reperfusion by targeting microvascular obstruction.

The IA-SUCCESS randomized trial aims to assess the clinical and safety of adjunct intra-arterial thrombolysis vs. no adjunct intra-arterial thrombolysis after successful angiographic reperfusion in patients with acute anterior circulation large vessel occlusion stroke.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Acute Ischemic
• Intervention / Treatment: Drug: Intra-arterial infusion of Alteplase

Detailed Description

Prospective phase 3 multicenter with open label blinded endpoint (PROBE) superiority randomized controlled trial, with health-economics evaluation.

The study strategy is to demonstrate the superiority of adjunct intra-arterial thrombolysis compared to no adjunct intra-arterial thrombolysis after successful angiographic reperfusion (eTICI 2b-2c-3) after intravenous alone, bridging therapy, or mechanical thrombectomy alone on 90-day functional outcome rate (shift of 90-day modified Rankin Scale toward a better functional outcome).

Patients with anterior circulation large vessel occlusion stroke will be recruited in the angiosuite by neurologists and/or neuroradiologists in participating centres after acute reperfusion therapy (intravenous thrombolysis alone, bridging therapy, or mecanical thrombectomy alone).

Patients enrolled in the experimental arm will receive intra-arterial thrombolysis with Alteplase. The dose of intra-arterial Alteplase is 0.225 mg/kg body weight and the maximal allowed dose is 20mg. Intra-arterial Alteplase will be injected through the guiding catheter placed in the internal carotid artery during 15 minutes.The total intra-arterial dose must be injected in the absence of complications.

Secondary objectives:

1. To assess the clinical and safety of adjunct intra-arterial thrombolysis.
2. To assess the cost-effectiveness of adjunct intra-arterial thrombolysis.
3. To assess the budget impact of new stroke management strategy in case of successful angiographic reperfusion.

• Study Type: Interventional
• Enrollment (Estimated): 626
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Benjamin GORY, MD, PHD; Phone Number: +33 +33 3 83 85 15 01; Email: b.gory@chru-nancy.fr
• Study Contact Backup: Name: Guillaume TURC, MD, PhD; Phone Number: +33 +33 1 45 65 86 65; Email: G.TURC@ghu-paris.fr

Study Locations

• France
  • Nancy, France, 54000
    • Recruiting
    • Chru Nancy
    • Contact: Benjamin GORY, MD, PhD
    • Principal Investigator: Benjamin GORY, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Pre-stroke mRS 0-2
• Acute ischemic stroke with anterior circulation large vessel occlusion defined as intracranial internal carotid artery, M1, or M2 occlusion proven on CT or MRI
• NIHSS score ≥ 5 at admission
• Acute reperfusion strategy started within 24h after stroke onset according to the international guidelines
• DWI-ASPECTS ≥ 2 (MRI) or CT-ASPECTS ≥ 3
• Delay from imaging to puncture within 3 hours for transferred patients
• eTICI 2b-2c-3 after intravenous thrombolysis alone, bridging therapy, or mechanical thrombectomy alone and confirmed by catheter angiogram
• Person affiliated to or beneficiary of a social security plan

Exclusion Criteria:

• Person who do not speak French
• Contraindications for intra-arterial thrombolysis: Platelet count <100 000/mm3, INR >1.7, AOD use <48h or biological confirmation of activity and effective heparin treatment
• Bleeding-risk complications during the mechanical thrombectomy procedure (e.g carotid dissection, complicated femoral approach)
• Bleeding-risk complications consecutive to a fall associated with stroke
• More than 5 thrombectomy device
• Intracerebral hemorrhage
• Occlusion or high grade stenosis treated by stenting
• Patient expected to be unable to present or be available for 3-month visit follow-up
• Participation in another clinical trial within 30 days prior to the inclusion which the experiment may affect the 90-day mRS score
• Woman of childbearing age without effective contraception
• Person referred in articles L.1121-5, L. 1121-7 and L.1121-8 of the French Public Health Code

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjunct intra-arterial thrombolysis; Adjunct intra-arterial thrombolysis with Alteplase 0.225mg/kg after intravenous thrombolysis intravenous thrombolysis alone, bridging therapy, or mechanical thrombectomy alone.	Drug: Intra-arterial infusion of Alteplase; Patients enrolled in the experimental arm will receive intra-arterial thrombolysis with Alteplase. The dose of Intra-arterial Alteplase is 0.225 mg/kg body weight with a maximal dose of 20 mg
No Intervention: No intra-arterial thrombolysis; Control group: no intra-arterial thrombolysis after intravenous thrombolysis alone, bridging therapy, or mechanical thrombectomy alone (according to standard of care).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The superiority of adjunct intra-arterial thrombolysis versus no adjunct intra-arterial thrombolysis	The primary endpoint is the severity of disability according to the distribution of scores on the modified Rankin Scale (mRS): mRS 0 to 6	90 (±15) days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the efficacy of adjunct intra-arterial thrombolysis	Distribution of the mRS score (0 to 6)	90 (±15) days
To assess the efficacy of adjunct intra-arterial thrombolysis	Excellent functional outcome (mRS 0-1)	90 (±15) days
To assess the efficacy of adjunct intra-arterial thrombolysis	Early neurological improvement (reduction in National Institutes of Health Stroke Scale (NIHSS) score by at least 8 points, or NIHSS score of 0-1)	24 (±6) hours
To assess the safety of adjunct intra-arterial thrombolysis	Symptomatic and asymptomatic intracerebral hemorrhage within 24-hour on imaging follow-up, according to the Heidelberg classification (imaging core laboratory).	24 (±6) hours
To assess the cost-effectiveness of adjunct intra-arterial thrombolysis	Incremental cost-effectiveness and cost-utility ratios of a strategy based on adjunct intra-arterial thrombolysis in case of successful angiographic reperfusion.	12 months
To assess the budget impact of new stroke management strategy in case of successful angiographic reperfusion	Total cost of each treatment strategy and net impact on the National Health Insurance System (difference in costs).	12 months

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): September 16, 2028
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: December 13, 2024
• First Submitted That Met QC Criteria: January 6, 2025
• First Posted (Actual): January 10, 2025

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Thrombectomy; Ischemic stroke; Endovascular treatment; Intra-arterial thrombolysis; Recanalisation
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Ischemic Stroke; Stroke; Ischemia; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: 2020PI054; 2023-506935-14-01 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No