IV rt-PA versus two-antiplatelet drug combo (DAPT) for small (lacunar) ischemic stroke

A Multicenter Randomized Controlled Trial Comparing Tissue Plasminogen Activator With Dual Antiplatelet Therapy for Patients With Hyperacute Single Perforating Artery Infarction

This trial will test whether a two-drug antiplatelet combination works as well as IV rt-PA and causes less bleeding for adults with a very small (lacunar) ischemic stroke treated within 4.5 hours.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 500 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Nippon Medical School (Academic / other)
• Locations: 27 sites (Chūō and 26 other locations)
• Trial ID: NCT07111559 on ClinicalTrials.gov

What this trial studies

This randomized, interventional Phase 4 trial compares dual antiplatelet therapy (DAPT) with standard intravenous tissue‑plasminogen activator (rt‑PA) in adults who have a single small perforating‑artery (lacunar) infarct confirmed on MRI within 4.5 hours of symptom onset. Eligible patients have mild deficits (NIHSS ≤ 5) and minimal pre‑stroke disability (mRS ≤ 1) and are randomized to receive either DAPT or IV rt‑PA. Investigators will monitor for functional recovery and bleeding complications and will check neurological status at 3 months in person, by phone, or by mail. The study is designed to see if DAPT is non‑inferior to rt‑PA for functional outcome and whether it lowers bleeding risk.

Who should consider this trial

Good fit: Adults (≥18) with an acute single lacunar ischemic stroke on MRI within 4.5 hours of last known well, NIHSS ≤ 5, pre‑stroke mRS ≤ 1, and able to provide informed consent are ideal candidates.

Not a fit: Patients with large‑vessel occlusion or ≥50% stenosis of the responsible artery, multiple or centrum semiovale‑only lesions, major bleeding risk or contraindications to antithrombotic therapy, onset >4.5 hours, or more severe deficits (NIHSS >5) are unlikely to benefit from this comparison.

Why it matters

Potential benefit: If successful, this could provide an equally effective treatment option with fewer bleeding complications for patients with lacunar stroke.

How similar studies have performed: Previous trials have shown that early DAPT reduces recurrent events after minor stroke or TIA, but using DAPT as an alternative to IV rt‑PA for acute lacunar stroke is novel and not previously proven in head‑to‑head trials.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years.
* Acute ischemic stroke within 4.5 hours from onset. If onset time is unknown because of impaired consciousness or aphasia, use the "last known well" time.
* A single perforating-artery infarct on brain MRI:

located in the corona radiata, putamen, internal capsule, thalamus, or pons; solitary, mainly round or oval, with a maximum diameter ≤ 20 mm; lesions only in the centrum semiovale are not allowed, but extension from the above sites into the centrum semiovale is allowed.

* No disability in daily life before the stroke (modified Rankin Scale ≤ 1).
* National Institutes of Health Stroke Scale (NIHSS) score ≤ 5.
* Written informed consent obtained.

Exclusion Criteria:

* Antithrombotic therapy considered inappropriate because of active bleeding, low platelet count, or similar conditions.
* Any contraindication to intravenous rt-PA, without blood pressures.
* ≥ 50 % stenosis or occlusion of the artery responsible for the stroke \* (see note below).
* Diseases that require anticoagulation (e.g., atrial fibrillation, deep-vein thrombosis) \*
* Inability to take medicine orally.
* Any other reason judged by the principal investigator or co-investigators to make participation inappropriate.

Note: This study targets hyper-acute stroke within 4.5 hours. To avoid treatment delay, items marked with \* must be judged using the similar examinations that each site normally performs before rt-PA administration.

Where this trial is running

Chūō and 26 other locations

• University of Yamanashi Hospital — Chūō, Japan (Recruiting)
• Fukuoka Red Cross Hospital — Fukuoka, Japan (Recruiting)
• Ota Memorial Hospital — Fukuyama, Japan (Recruiting)
• Kansai Medical University Hospital — Hirakata, Japan (Recruiting)
• Kagoshima City Hospital — Kagoshima, Japan (Recruiting)
• Kagoshima Medical Center — Kagoshima, Japan (Recruiting)
• Shioda Hospital — Katsuura, Japan (Recruiting)
• St. Marianna University School of Medicine Hospital — Kawasaki, Japan (Recruiting)
• The Jikei University West Medical Center — Komae, Japan (Recruiting)
• Kawasaki Medical School Hospital — Kurashiki, Japan (Recruiting)
• Japanese Red Cross Kyoto Daini Hospital — Kyoto, Japan (Recruiting)
• University Hospital Kyoto Prefectural University of Medicine — Kyoto, Japan (Recruiting)
• The Jikei University Hospital — Minatoku, Japan (Recruiting)
• Kawasaki Medical School General Medical Center — Okayama, Japan (Recruiting)
• Kohnan Hospital — Sendai, Japan (Recruiting)
• Jichi Medical University Hospital — Shimotsuke, Japan (Recruiting)
• Nippon Medical School Tamanagayama hospital — Tama, Japan (Recruiting)
• Dokkyo Medical University Hospital — Tochigi, Japan (Recruiting)
• Tokushima University Hospital — Tokushima, Japan (Recruiting)
• Juntendo University Hospital — Tokyo, Japan (Recruiting)
• Nippon Medical School hospital — Tokyo, Japan (Recruiting)
• Science Tokyo Hospital — Tokyo, Japan (Recruiting)
• Tokyo Rosai Hospital — Tokyo, Japan (Recruiting)
• Tokyo Saiseikai Central Hospital — Tokyo, Japan (Recruiting)
• Tokyo Women's Medical University Hospital — Tokyo, Japan (Recruiting)
• Yamaguchi University Hospital — Ube, Japan (Recruiting)
• Juntendo University Urayasu Hospital — Urayasu, Japan (Recruiting)

Study contacts

• Principal investigator: Yuki Sakamoto — Nippon Medical School
• Study coordinator: Yuki Sakamoto

Conditions Lacunar Stroke; Stroke; Ischemic Stroke; rt-PA; tissue-plasminogen activator; DAPT; dual antiplatelet therapy