OPtimizing REperfusion by Intra-Arterial ThRomboLysis as Adjunct to Endovascular Treatment for Medium Vessel Occlusion

Official title

OPtimizing REperfusion by Intra-Arterial ThRomboLysis as Adjunct to Endovascular Treatment for Medium Vessel Occlusion (PEARL-MeVO): A Multicenter, Prospective, Randomized Controlled, Open-label, Blinded-Endpoint Clinical Trial

Overview

PEARL-MeVO is an investigator-initiated, multicenter, prospective, randomized controlled, open-label, blinded endpoint (PROBE) clinical trial aiming at evaluating the efficacy and safety of intra-arterial thrombolysis as adjunct to endovascular treatment in improving 90-day functional outcome in acute ischemic stroke patients due to medium vessel occlusion (MeVO) within 24 hours of symptom onset.

Detailed description

PEARL-MeVO is an investigator-initiated, multicenter, prospective, randomized controlled, open-label, blinded endpoint (PROBE) clinical trial aiming at evaluating the efficacy and safety of intra-arterial thrombolysis as adjunct to endovascular treatment in improving 90-day functional outcome in acute ischemic stroke patients due to medium vessel occlusion (MeVO) within 24 hours of symptom onset. The primary outcome is the proportion of patients with a 90-day modified Rankin Scale (mRS) of 0-1. Eligible patients will be randomly assigned at a ratio of 1:1 into the intervention group to receive intra-arterial thrombolysis as adjunct to endovascular treatment, or the control group to receive only standard medical management. A total of 530 participants (265 per group) are anticipated to be recruited for this study.

Interventions

• Combination product Intra-arterial thrombolysis as adjunct to endovascular treatment
  Intra-arterial thrombolysis as adjunct to endovascular treatment, in addition to standard medical treatment
• Other Standard medical treatment
  Standard medical treatment

Primary outcome measures

• The modified Rankin Scale score (mRS) 0-1 [Time frame: 90 (±14) days]

Secondary outcome measures (4)

• Level of disability [Time frame: 90 (±14) days]
• The modified Rankin Scale score (mRS) 0-2 [Time frame: 90 (±14) days]
• Quality of life (EQ-5D-5L) [Time frame: 90 (±14) days]
• Neurologic deficit (NIHSS score) changes [Time frame: 24 (±12) hours]

Eligibility criteria

Inclusion criteria

• Aged 18 years or older.
• Clinical diagnosis of acute ischemic stroke.
• CT angiography (CTA) or MR angiography (MRA) confirmed primary isolated medium vessel occlusion (i.e. an occlusion of the co-/non-dominant M2, the M3/M4 segment of the MCA, the A1/A2/A3 segment of the ACA, or the P1/P2/P3 segment of the PCA).
• Baseline NIHSS ≥6.
• Treatment (arterial puncture) can be initiated 5.1 Within 6 hours of last known well (LKW) OR 5.2 Within 6 to 24 hours of LKW AND evidence of salvageable brain tissue on CT perfusion or perfusion-diffusion MRI (ischemic core volume <50mL, hypo-perfused tissue volume to ischemic core volume ratio >1.4, mismatch volume >10mL). Hypo-perfused tissue is defined as Tmax >6s on CT perfusion or perfusion MRI. Ischemic core is defined as rCBF <30% on CT perfusion or ADC <620μm2/s on diffusion MRI.
• Signed informed consent.

Exclusion criteria

• Evidence of intracranial hemorrhage.
• Pre-stroke mRS score ≥ 2.
• Rapidly improving symptoms, in the judgment of the managing clinician that the improvement is likely to result in the patient having an NIHSS score of <6 at randomization.
• The intervention procedure is unlikely to be completed as assessed by the investigator.
• Suspected cerebral vasculitis, septic embolization, or vascular occlusion due to infective endocarditis.
• Suspected arterial dissection.
• Severe allergy to contrast agents (non-mild rash allergy) or absolute contraindication to iodine contrast.
• Known genetic or acquired bleeding disposition or anticoagulant factors deficiency.
• Coagulation disorder with INR >1.7 or use of new oral anticoagulants within 48 hours prior to symptom onset.
• Platelet count <50×10\^9/L.
• Any active or recent bleeding (gastrointestinal, urinary tract bleeding, etc.), or previous parenchymal organ surgery or biopsy in the last 1 month.
• Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, refractory to treatment.
• Known severe renal insufficiency with glomerular filtration rate <30 ml/min or blood creatinine >220 μmol/L (2.5 mg/dl).
• Radiological confirmed evidence of mass effect or intracranial tumour (except small meningioma).
• Anticipated life expectancy <6 months due to advanced disease (e.g., malignancy, severe cardiopulmonary disease, etc.).
• Women who are pregnant or breastfeeding.
• Participation in other clinical trials.
• Any condition that, in the judgment of the investigator, makes the patient unsuitable for this study or where this study may impose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric disorders, cognitive or emotional impairment).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou

Identifiers

NCT: NCT07137832 · SYSKY-2025-574-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗