OPTION
(2026)Objective
To assess the efficacy and safety of intravenous tenecteplase (0.25 mg/kg) administered 4.5–24 hours after stroke onset in patients with non-large vessel occlusion acute ischemic stroke and salvageable brain tissue on CT perfusion imaging
Study Summary
• Benefit was consistent across subgroups including anterior/posterior circulation, time windows, and stroke severity; ordinal mRS shift also favored tenecteplase (common OR 1.39; P=.03)
• Symptomatic ICH was significantly higher with tenecteplase: 2.8% vs 0% (P=.004); mortality was numerically higher (5.0% vs 3.2%) but not significant (P=.28).
Intervention
IV tenecteplase 0.25 mg/kg (max 25 mg) bolus vs standard medical treatment, in patients with CTP-confirmed perfusion-core mismatch, 4.5–24 hours from last seen well
Inclusion Criteria
Age ≥18, prestroke mRS 0–1, NIHSS 6–25 (or 4–5 with disabling deficit), non-LVO (no ICA, M1, or vertebrobasilar occlusion), CTP mismatch (core <50 mL, mismatch ratio ≥1.2, mismatch volume ≥10 mL), treatable 4.5–24 h from last seen well
Study Design
Arms: Tenecteplase 0.25 mg/kg IV, Standard medical treatment
Patients per Arm: Tenecteplase 282, Standard medical treatment 284
Outcome
• Secondary: ordinal mRS shift favored TNK (common OR 1.39; P=.03); 24-h reperfusion 37.7% vs 28.8% (P=.03); early clinical response 11.4% vs 5.0% (P=.007); mRS 0–2 nominally higher 62.8% vs 55.3% (P=.07)
• Safety: sICH 2.8% vs 0% (P=.004); 90-d mortality 5.0% vs 3.2% (P=.28)
Bottom Line
IV tenecteplase at 4.5–24 hours significantly increased the rate of excellent functional outcome (mRS 0–1) at 90 days compared with standard medical treatment (43.6% vs 34.2%; RR 1.28; P=.02; NNT=11). The ordinal mRS shift, 24-hour reperfusion, and early clinical response all favored tenecteplase. However, symptomatic ICH was significantly higher (2.8% vs 0%; P=.004), and 90-day mortality was numerically but not significantly increased (5.0% vs 3.2%; P=.28). This is the first trial to demonstrate benefit of late-window thrombolysis specifically in non-LVO stroke selected by perfusion imaging, complementing TRACE-III (LVO without thrombectomy access) and HOPE (mixed population with alteplase).
Major Points
- OPTION was a multicenter, randomized, open-label, blinded-endpoint trial at 48 Chinese centers enrolling 566 patients with non-LVO AIS and CTP-confirmed salvageable tissue at 4.5–24 hours (June 2023–August 2025)
- Primary endpoint met: mRS 0–1 at 90 days in 43.6% tenecteplase vs 34.2% control (RR 1.28; 95% CI 1.04–1.57; P=.02; adjusted RR 1.32; P=.007; NNT=11)
- Ordinal mRS shift favored tenecteplase (common OR 1.39; 95% CI 1.04–1.86; P=.03); functional independence (mRS 0–2) was 62.8% vs 55.3% (RR 1.14; P=.07, nominally nonsignificant)
- 24-hour reperfusion: 37.7% vs 28.8% (RR 1.31; P=.03); early clinical response at 24 h: 11.4% vs 5.0% (RR 2.30; P=.007)
- Symptomatic ICH (Heidelberg): 2.8% vs 0% (RD 2.85%; P=.004); 2 of 21 patients with mismatch inconsistency (CT hypodensity > CTP core) developed sICH
- 90-day mortality: 5.0% vs 3.2% (RR 1.57; P=.28, not significant); moderate/severe systemic bleeding: 0.7% in both groups
- Most common qualifying arteries: M2 (31.6%), anterior cerebral artery (15.2%), posterior cerebral artery (13.8%), M3-M4 (7.6%); 23.3% had stenosis without occlusion
- Median onset-to-randomization was 12.0 hours; 32% were wake-up strokes; median NIHSS 7 (IQR 5–9); median ischemic core volume 0–1 mL (very small cores)
- No treatment effect heterogeneity across 7 prespecified subgroups (age, time window, NIHSS, circulation, qualifying artery, glucose, SBP) or post hoc stroke etiology subgroup
- Post hoc analysis of patients meeting ESCAPE-MeVO/DISTAL criteria (68.2%): mRS 0–1 42.6% vs 33.0% (RR 1.29; P=.054, approaching significance)
Study Design
- Study Type
- Multicenter, randomized, open-label, blinded-endpoint (PROBE) clinical trial
- Randomization
- Yes
- Blinding
- Open-label treatment assignment. Blinded outcome assessment: mRS at 90 days obtained by structured telephone interview by blinded assessors; audio recordings reviewed by independent blinded neurologist. Imaging adjudicated at independent core lab.
- Sample Size
- 566
- Follow-up
- 90 days
- Centers
- 48
- Countries
- China
Primary Outcome
Definition: Excellent functional outcome defined as mRS 0 or 1 at 90 days, assessed by blinded telephone interview with independent audio review
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 97/284 (34.2%) | 123/282 (43.6%) | - (1.04 to 1.57 (adjusted 1.08 to 1.61)) | .02 (adjusted .007) |
Limitations & Criticisms
- Open-label design, though outcomes were assessed by blinded assessors with independent audio review — residual performance bias possible
- Conducted exclusively in Chinese population (48 centers); generalizability to other races/ethnicities is uncertain
- Symptomatic ICH rate of 2.8% vs 0% is concerning; 2 of 21 patients with mismatch inconsistency (CT hypodensity exceeding CTP core) developed sICH, suggesting careful NCCT review is critical
- Functional independence (mRS 0–2) did not reach significance in unadjusted analysis (P=.07), though adjusted analysis was significant (P=.03)
- 23.3% of patients had stenosis without occlusion rather than true MeVO/distal occlusion — mixed pathophysiology
- Very small ischemic cores (median 0–1 mL) indicate a highly selected favorable population; benefit may not extend to those with larger cores
- Planned interim analysis was not conducted due to rapid enrollment — no α was spent but deviates from original statistical plan
- Rescue thrombectomy was permitted (6 tenecteplase, 1 control) — though post hoc analysis adjusting for this showed consistent results
- CTP software (CTPdoc, Shukun Technology) is not widely validated outside China; posterior circulation CTP thresholds are not well established
- 90-day mortality was numerically higher with tenecteplase (5.0% vs 3.2%), and the trial was not powered to assess mortality as a safety endpoint
- Dominant M2 occlusions were not excluded despite emerging thrombectomy evidence for this subgroup (ESCAPE-MeVO, DISTAL)
Citation
JAMA. 2026. doi:10.1001/jama.2026.0210