Tirofiban with sequential dual antiplatelet therapy in mild acute ischemic stroke (TiMIS): protocol for a multicenter, randomized controlled trial.

Patients with mild acute ischemic stroke remain at substantial risk for early neurological deterioration and poor functional outcomes despite receiving standard dual antiplatelet therapy.

• Mild AIS is defined as NIHSS score ≤5
• Standard care consists of dual antiplatelet therapy (DAPT)
• The paper identifies this population as 'prevalent yet undertreated'
• Early neurological deterioration (END) is identified as a key risk despite current standard treatment

The TiMIS trial is designed as a prospective, multicenter, open-label, blinded-endpoint (PROBE) randomized controlled study enrolling 688 patients across 20 centers in China.

• Total planned enrollment is 688 patients
• Participants are aged 18-80 years with noncardioembolic acute mild ischemic stroke
• Patients must be within 48 hours of symptom onset at enrollment
• Randomization is 1:1 to intervention or control
• The study is conducted across 20 centers in China

The intervention arm receives intravenous tirofiban for 48 hours sequentially followed by dual antiplatelet therapy, compared to dual antiplatelet therapy alone in the control arm.

• Tirofiban is described as 'a rapid-onset glycoprotein IIb/IIIa receptor inhibitor'
• Tirofiban is administered intravenously for 48 hours
• After the 48-hour tirofiban period, patients transition to DAPT (sequential therapy)
• The 48-hour window is described as 'a critical window for preventing disability'
• Evidence for tirofiban use specifically in mild AIS is described as 'limited'

The primary outcome of the TiMIS trial is the proportion of patients with excellent functional outcomes (mRS score 0-1) at 90 days.

• Excellent functional outcome is defined as modified Rankin Scale (mRS) score of 0-1
• The assessment time point is 90 days post-randomization
• The outcome compares tirofiban plus sequential DAPT versus DAPT alone

Secondary outcomes include early neurological deterioration, NIHSS score changes, good functional outcome, mRS score shift, incidence of new ischemic stroke, and composite cardiovascular events.

• Secondary efficacy outcomes include END, changes in NIHSS score, good functional outcome, and mRS score shift
• Incidence of new ischemic stroke is a secondary outcome
• Composite cardiovascular events are also assessed as a secondary outcome
• Safety endpoints include symptomatic intracerebral hemorrhage, all-cause mortality, and severe bleeding events