Day 1 Clinical Trials Highlights at WSC 2026

covered by Virginia Cancelloni

Successful reperfusion following mechanical thrombectomy does not always translate into favourable functional outcomes, potentially due to residual distal emboli, impaired microvascular perfusion, and persistent tissue-level injury. Recent randomised trials, including CHOICE, PEARL, CHOICE-2, and ANGEL-TNK, have investigated adjunctive intra-arterial thrombolysis following mechanical thrombectomy, providing encouraging evidence for this approach.

The original PEARL trial demonstrated that adjunctive intra-arterial alteplase significantly improved excellent functional outcomes (90-day mRS 0–1) compared with standard care following mechanical thrombectomy (44.8% vs 30.2%).

At WSC 2026, Professor Tang from Taiwan presented a post hoc analysis of the PEARL trial focusing on 136 patients who achieved near-complete or complete reperfusion (eTICI 2c–3), providing further insights into the potential benefits of adjunctive intra-arterial thrombolysis.

Excellent functional outcomes (mRS 0–1) were achieved in 54.7% of patients receiving intra-arterial alteplase compared with 31.0% of those receiving standard care (RR 1.81; 95% CI 1.14–2.87; p=0.01). Functional independence (mRS 0–2) was also more frequent in the alteplase group (67.2% vs 47.9%). Importantly, symptomatic intracranial haemorrhage occurred in 1.5% versus 5.6% of patients, respectively, with no statistically significant difference between groups.

Professor Tang also presented an update on the ongoing PEARL-TNK trial, a multicentre, randomised, double-blind, placebo-controlled study evaluating adjunctive intra-arterial TNK in patients with anterior circulation large-vessel occlusion (LVO) and incomplete reperfusion (eTICI 2b50–2b67) following mechanical thrombectomy. Participants are randomised to receive intra-arterial TNK or placebo, alongside standard medical care. The primary endpoint is excellent functional outcome (mRS 0–1) at 90 days, while secondary and safety outcomes include the ordinal mRS distribution, functional independence, symptomatic intracranial haemorrhage, and mortality. As of October 3, 2026, 92 of the planned 468 patients had been enrolled, with 49 participating centres across 12 Chinese provinces.

Finally, Professor Tang introduced the ongoing PEARL-MeVO trial, addressing another important area of uncertainty in acute stroke treatment. Recent randomised trials have yielded conflicting results regarding the benefits of mechanical thrombectomy in MeVO. PEARL-MeVO is investigating the role of an intra-arterial thrombolysis-based strategy in patients with MeVO. The trial aims to enrol 530 adults presenting within 24 hours of last known well, with an NIHSS score ≥6 and eligible occlusions involving the M2, M3/M4, A1–A3, or P1–P3 segments. Participants are randomised to intra-arterial TNK, with optional mechanical thrombectomy when considered feasible and safe, or standard medical treatment. At the time of the congress, 474 of the planned 530 patients had been enrolled, with 114 activated centres across 26 Chinese provinces.

We eagerly await the results of PEARL-TNK and PEARL-MeVO, which may provide pivotal evidence to refine reperfusion strategies, address the limitations of angiographic success, and ultimately improve functional outcomes in patients with acute ischaemic stroke.

TAPIS Trial: Can DWI Patterns Guide Early Antiplatelet Therapy After Thrombolysis?

Covered by Marla Gallo Guerrero

A subgroup analysis of the TAPIS trial, presented by Xiaohui Zi at the 18th World Stroke Congress, evaluated whether DWI infarction patterns influence the efficacy and safety of early ticagrelor–aspirin following intravenous thrombolysis.

Methods: Among 1,307 patients with non-cardioembolic ischaemic stroke (NIHSS 4–10), 409 (31.3%) had multiple acute infarctions (MAIs) and 898 (68.7%) had non-MAI patterns.

Key findings:

• Prognosis: Patients with MAIs had lower rates of excellent functional outcome (mRS 0–1 at 90 days: 58.9% vs 69.2%) and a higher adverse-event burden.
• Primary efficacy: In the MAI subgroup, early ticagrelor–aspirin increased mRS 0–1 rates compared with placebo (64.4% vs 53.4%; RR 1.21, 95% CI 1.02–1.42). No significant benefit was observed in non-MAIs (71.2% vs 67.1%; RR 1.06, 95% CI 0.97–1.16). However, the primary treatment-by-pattern interaction was not significant (P=0.1788).
• Neurological improvement: In patients with MAIs, NIHSS improvement ≥4 points at day 7 was more frequent with ticagrelor–aspirin (57.6% vs 45.6%; RR 1.26, 95% CI 1.04–1.53; P for interaction=0.02).
• Safety: No statistically significant increase in symptomatic intracranial haemorrhage or overall bleeding was detected across infarction patterns.
• Sensitivity analysis: Accounting for rescue tirofiban suggested a stronger treatment effect in MAIs (adjusted RR 1.32, 95% CI 1.11–1.58; P for interaction=0.042), although this finding remains exploratory.

Clinical takeaway: Multiple acute DWI lesions identify a higher-risk stroke phenotype that may derive greater benefit from early dual antiplatelet therapy after thrombolysis. However, the absence of a significant primary interaction and the exploratory nature of the analyses preclude immediate changes in clinical practice.

The key message: DWI infarction patterns are promising imaging biomarkers for future trials of personalised antiplatelet strategies after reperfusion therapy.

Safety And Exploratory Efficacy of Intra-Arterial Methylprednisolone After Successful Thrombectomy: The RAPID-M Randomized Pilot Trial

Covered by Seblewongel Asmare Seyoum

RAPID-M was a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) pilot trial evaluating selective intra-arterial methylprednisolone immediately after successful endovascular thrombectomy for anterior-circulation large-vessel occlusion. Adults with NIHSS ≥6, ASPECTS ≥3 and successful reperfusion were randomized 1:1 to methylprednisolone (n=69) or volume-matched saline placebo (n=71). The intervention was a single intra-arterial dose of 0.5 mg/kg (maximum 60 mg), infused at 3 mL/min.

Primary exploratory efficacy endpoint: 90-day modified Rankin Scale (mRS) distribution. The trial aimed to assess whether targeted glucocorticoid delivery after reperfusion was feasible and safe, and to explore its potential effect on post-stroke functional recovery.

Efficacy: The adjusted common odds ratio for a favorable shift in 90-day mRS was 1.29 (95% CI 0.72–2.32; p=0.40), numerically favoring methylprednisolone but not statistically significant. Exploratory subgroup analyses showed no reliable evidence of differences in treatment effect across assessed patient characteristics. A predictive probability of success analysis estimated 57.5% statistical success for a hypothetical phase III trial under modelled assumptions; this was for decision support, not evidence of efficacy.

Safety / tolerability: All 140 patients received their allocated infusion, with zero technical failures or infusionrelated complications; 139/140 (99.3%) completed 90-day follow-up. All-cause mortality: 15.9% with methylprednisolone vs 18.6% with placebo; symptomatic intracranial hemorrhage: 8.7% vs 12.7%. Post-stroke pneumonia: 37.7% vs 35.2%; severe hyperglycemia: 4.3% vs 2.8%; gastrointestinal bleeding: 4.3% vs 4.2%. No consistent excess safety signal was observed; the pilot sample was not large enough to establish definitive safety or efficacy.

Conclusion. In RAPID-M, selective intra-arterial methylprednisolone following successful thrombectomy was feasible, with no consistent excess safety signal. Although exploratory efficacy estimates favored treatment numerically, the results were inconclusive. Further dose-ranging and mechanistic investigation is warranted rather than direct confirmatory evaluation of the current regimen.

PILOT STUDY FOR SMARTWATCH-DRIVEN ATRIAL FIBRILLATION DETECTION IN STROKE PATIENTS: FIND AF 2 TRIAL

Covered by Deise Catamo Vaz

Wearable strategies for AF detection are comparable to implantable monitors, with frequency of charging influencing wear time and detection sensitivity.

Study design and hypotheses

• The study compares wearable device performance to continuous implantable ECG monitoring for AF detection after stroke.
• It hypothesizes that wearables can match implantable monitors in detection probability.
• The trial includes randomization of participants to different wearable charging schedules.
• Primary endpoints focus on sensitivity of AF detection based on episode duration.

Population and trial methods

• The study enrolled 155 stroke patients, with 60 randomized to wearable devices.
• Participants had a median follow-up of four years, with inclusion criteria based on stroke and AF history.
• Patients underwent check-in, consent, and randomization procedures, with follow-up visits scheduled.

Devices and monitoring strategies

• Apple Watch and PulseOn wearable devices used for AF monitoring.
• Devices employed photoplethysmography and ECG at set times, with visual or vibration alerts.
• Data transmission occurred via phone apps, with centralized review of all episodes.
• Implantable cardiac monitors were used as the reference standard for AF detection.

Study outcomes and findings

• The primary endpoint measured AF detection sensitivity, with results showing no significant device difference.
• Wearable AF detection strongly depended on episode duration.
• Less frequent charging correlated with longer wear time and higher detection sensitivity.
• High adherence and wear time demonstrated feasibility in post-stroke patients.

Limitations and conclusions

• The study’s generalizability was limited to German, relatively healthy stroke populations.
• Results support wearable use as a feasible, complementary AF monitoring approach post-stroke.
• Longer episode detection improved with less frequent charging, without device differences.