Interactive Door-to-Discharge Clinical Trial Decision Simulator, 6-Phase Trial Workflow, TNK 0.25 mg/kg bolus evidence, and sICH reversal
Select the patient's presentation, time window, imaging/vessel profile, and etiology below to generate the exact step-by-step management protocol and landmark trial evidence.
ADMINISTER IV THROMBOLYSIS IMMEDIATELY (Door-to-Needle ≤45 min): Give IV Tenecteplase (TNK) 0.25 mg/kg single 5-sec bolus (max 25 mg) OR IV Alteplase 0.9 mg/kg (max 90 mg: 10% bolus + 90% over 60 min). Ensure BP < 185/110 mmHg before bolus.
PROCEED IMMEDIATELY TO MECHANICAL THROMBECTOMY (Bridging IVT + EVT): Early-window ICA/M1 occlusion with ASPECTS ≥6 (HERMES Meta-analysis: NNT = 2.6! Do NOT skip IVT per IRIS/SWIFT-DIRECT).
Pre-IVT/EVT: <185/110 mmHg | Post-EVT (mTICI 2b–3): Maintain SBP 140–180 mmHg (AVOID intensive SBP <120–140 mmHg — HARM in ENCHANTED2/MT & OPTIMAL-BP 2023!)
Atrial Fibrillation Cardioembolic Stroke: Initiate DOAC (Apixaban, Dabigatran, Rivaroxaban, or Edoxaban — preferred over Warfarin unless mechanical valve or moderate-severe rheumatic MS). Timing per ELAN (2023) & OPTIMAS (2024): Start Day 2–4 (≤48h) for minor/small infarct, Day 4–7 for moderate infarct, or Day 6–14 for large territorial infarct after repeat CT excludes PH1/PH2.
Complete chronological clinical pathway from ED Door (Phase 1) → IVT (Phase 2) → EVT (Phase 3) → Neuro-ICU/BP (Phase 4) → Secondary Prevention (Phase 5) → Hemorrhagic/Venous Pathways (Phase 6)
Rapid airway/hemodynamic stabilization, exclude hypoglycemia, determine exact Last Known Well (LKW) time, and perform STAT Non-Contrast CT + CTA Head/Neck (± CTP).
SHINE (n=1,151): Intensive IV insulin (target 80–130 mg/dL) did NOT improve 90-day functional outcome vs standard control (140–180 mg/dL) (20.5% vs 21.6%) and caused severe hypoglycemia (2.6% vs 0%).
Every 15-minute reduction in door-to-reperfusion increases odds of independent ambulation and discharge home.
In 0–6h anterior LVO with ASPECTS ≥6, do NOT delay EVT groin puncture to obtain CTP.
Lower BP < 185/110 mmHg before bolus (maintain < 180/105 mmHg x 24h). Select IVT agent and time-window protocol based on symptom severity and tissue clock.
AcT (n=1,600): TNK 0.25 mg/kg non-inferior to Alteplase (mRS 0–1: 36.9% vs 34.8%). EXTEND-IA TNK: Double early LVO recanalization prior to EVT (22% vs 10%).
PRISMS: Alteplase did not improve 90d mRS 0–1 vs Aspirin (78.2% vs 81.5%) with higher sICH (3.2% vs 0%). ARAMIS (n=760): DAPT non-inferior to IV Alteplase (93.8% vs 91.4% mRS 0–1) with less bleeding.
WAKE-UP: mRS 0–1 53.3% vs 41.8% (OR 1.61). EXTEND: mRS 0–1 35.4% vs 29.5% (aRR 1.44).
TRACE-III (n=516): TNK at 4.5–24h without EVT significantly increased 90-day mRS 0–1 (33.0% vs 24.2%, RR 1.37). Note: If going directly to immediate EVT, TIMELESS showed neutral added benefit of late TNK.
Non-inferiority of skipping IVT was NOT established across pooled RCTs; bridging therapy achieves higher pre-EVT and final successful reperfusion.
Activate Neuro-Interventional team in parallel with IVT. Select patients using vessel location (ICA, M1, Basilar), time from LKW, ASPECTS, and CTP core-penumbra profile.
HERMES (n=1,287): cOR 2.49 for 90-day functional improvement; 90d mRS 0–2 46.0% vs 26.5% (NNT = 2.6 for 1-point mRS reduction!).
DAWN: 90d mRS 0–2 49% vs 13% (NNT = 2.8!). DEFUSE 3: 90d mRS 0–2 45% vs 17% (NNT = 3.6!).
SELECT2 & ANGEL-ASPECT: EVT doubled functional independence (mRS 0–2 ~20–30% vs ~7–12%) and independent ambulation (mRS 0–3) despite large baseline core.
ATTENTION (0–12h): 90d mRS 0–3 46% vs 23% (aRR 2.06) and mortality reduced from 55% to 37%. BAOCHE (6–24h): mRS 0–3 46% vs 24%.
Both 2025 RCTs showed no functional benefit of routine EVT over best medical therapy for distal MeVOs, with higher sICH.
Tailor blood pressure targets strictly to recanalization status (mTICI score), monitor for hemorrhagic transformation on 24h CT, and intervene early for malignant edema.
ENCHANTED2/MT & OPTIMAL-BP were both stopped early for HARM: intensive SBP <120 or <140 mmHg after successful EVT worsened 90-day disability (OR 1.37 for poor outcome) by hypoperfusing microcirculatory penumbra.
Aggressive early BP lowering in non-recanalized AIS compromises collateral perfusion without reducing recurrent stroke.
Pooled DECIMAL/DESTINY/HAMLET (Age ≤60, ≤48h): Mortality reduced from 78% to 29% (NNT = 2 for survival!). DESTINY II (Age >60): Reduced mortality (33% vs 70%), though more survivors had mRS 4.
After 24h post-tPA/TNK CT excludes hemorrhage, initiate tailored secondary prevention matched to TOAST mechanism, NIHSS severity, CYP2C19 genotype, and infarct size.
CHANCE & POINT: 28–32% reduction in 90d stroke; benefit occurs in first 21 days, while bleeding rises after Day 21. CHANCE-2: Ticagrelor+ASA cut stroke by 23% vs Clopidogrel+ASA in CYP2C19 LOF carriers.
SAMMPRIS: Wingspan stenting caused 14.7% vs 5.8% 30-day stroke/death. TST Trial: LDL <70 mg/dL significantly reduced major cardiovascular events vs LDL 90–110 mg/dL (HR 0.78).
NASCET (70–99%): 2-yr ipsilateral stroke reduced from 26% to 9% (17% ARR). CREST: CEA had lower periprocedural stroke; CAS had lower periprocedural MI; age <70 favored CAS, age >70 favored CEA.
ELAN (n=2,013) & OPTIMAS (n=3,648): Early DOAC initiation (≤48h minor/moderate; Day 6–7 large) was safe and numerically reduced recurrent ischemic stroke without increasing sICH vs delayed 1-3-6-12 rule.
NAVIGATE ESUS, RE-SPECT ESUS & ARCADIA proved empiric DOAC fails without documented AFib. CLOSE/REDUCE/DEFENSE-PFO proved PFO closure slashes recurrent stroke by ~70–90% in high-risk PFO.
When initial neuroimaging reveals primary hemorrhage or venous thrombosis, pivot immediately to the corresponding evidence-based trial bundle.
INTERACT3 (n=7,036): Physiological care bundle reduced poor outcome & death (OR 0.86). ENRICH (2024): First positive surgical RCT for lobar ICH 30–80 mL within 24h using Minimally Invasive Parafascicular Surgery.
Nimodipine reduces delayed cerebral ischemia (DCI) and poor outcome by 34%. ISAT: Endovascular coiling reduced 1-yr dependency/death by 23.9% RRR vs surgical clipping.
RESPECT-CVT & ACTION-CVT: DOACs match Warfarin efficacy with lower major bleeding. TO-ACT: Routine endovascular thrombectomy did NOT improve outcome over standard anticoagulation.
Door-to-Needle Target ≤ 45–60 min | Pre-treatment BP MUST be < 185/110 mmHg (Maintain < 180/105 mmHg x 24h)
Evidence: NINDS (0–3h: 30% relative increase in mRS 0–1, sICH ~6%), ECASS III (3–4.5h: OR 1.34 for favorable outcome).
Evidence: Higher fibrin specificity & longer half-life. Non-inferior/superior recanalization vs Alteplase (AcT, EXTEND-IA TNK, TRACE-2). WARNING: Never use 0.4 mg/kg cardiac dose (NOR-TEST 2 showed increased sICH).
In patients with unknown onset or wake-up stroke, a positive DWI lesion with NO visible parenchymal hyperintensity on FLAIR indicates tissue clock <4.5h → IV Alteplase significantly improved 90-day mRS 0–1 (53.3% vs 41.8%).
IV Alteplase between 4.5–9h (or wake-up within 9h of midpoint of sleep) selected by automated perfusion (Core <70 mL, Mismatch ratio >1.2, Mismatch volume >10 mL) improved functional independence (aRR 1.44).
IV Tenecteplase (0.25 mg/kg) administered 4.5–24h after onset in ICA/MCA LVO with salvageable perfusion mismatch when immediate thrombectomy was unavailable significantly increased 90-day mRS 0–1 (33.0% vs 24.2%).
Suspect if acute neurological deterioration (NIHSS +4), severe headache, nausea/vomiting, or acute BP spike occurs during or within 24h of infusion: