TEMPO-2 Recanalization
(2026)Objective
In minor ischemic stroke (NIHSS 0–5) with proven intracranial occlusion enrolled in TEMPO-2, evaluate whether successful early recanalization on 4–8 hour follow-up CTA is associated with better 90-day functional outcomes, and identify predictors of successful recanalization.
Study Summary
• Tenecteplase was the strongest independent predictor of successful recanalization (OR 3.48, 95% CI 2.33–5.18); 23.6% recanalized on tenecteplase vs 10.8% on standard care.
• Stroke progression was markedly lower with successful recanalization (2.8% vs 13.1%; adjusted RR 0.21, 95% CI 0.08–0.52) with no increase in symptomatic ICH or serious safety events.
Intervention
Secondary analysis of TEMPO-2 comparing patients with successful vs unsuccessful early recanalization (revised Arterial Occlusive Lesion score ≥2b/3 on 4–8 hour CTA); underlying trial randomized intravenous tenecteplase 0.25 mg/kg vs nonthrombolytic standard of care.
Inclusion Criteria
Adults with acute minor ischemic stroke (NIHSS score 0–5), CT angiography evidence of intracranial arterial occlusion, within 12 hours of symptom onset, prestroke mRS ≤2, and follow-up CTA at 4–8 hours after randomization.
Study Design
Arms: Successful recanalization (rAOL 2b/3) vs unsuccessful recanalization on follow-up CTA, stratified by tenecteplase vs standard of care.
Patients per Arm: Successful recanalization: 178 (122 tenecteplase, 56 control); unsuccessful recanalization: 336 (134 tenecteplase, 202 control); total analyzed 517 of 886 randomized.
Outcome
• Stroke progression: 2.8% vs 13.1%, adjusted RR 0.21 (95% CI 0.08–0.52); SAE 15.2% vs 28.0%, adjusted RR 0.54 (95% CI 0.37–0.80).
• EQ-5D-5L index higher with recanalization (0.86 vs 0.79; adjusted diff 0.06, 95% CI 0.02–0.11); no significant difference in mortality or symptomatic ICH.
Clinical Question
In minor ischemic stroke (NIHSS 0–5) with proven intracranial occlusion, is early successful recanalization (rAOL 2b/3 on 4–8 hour follow-up CTA) associated with improved 90-day functional outcomes, and what patient/treatment factors predict recanalization?
Bottom Line
Early successful recanalization independently predicts better 90-day functional outcomes in minor ischemic stroke with proven occlusion (adjusted RR 1.21), and intravenous tenecteplase is the strongest predictor of achieving recanalization (OR 3.48), although only a minority (23.6%) of tenecteplase-treated patients recanalized and treatment-level differences in 90-day outcomes were not statistically significant.
Major Points
- Post hoc analysis of TEMPO-2 (NCT02398656): 517 of 886 randomized patients had baseline CTA occlusion plus 4–8 hour follow-up CTA and were included.
- Successful recanalization (rAOL ≥2b/3) occurred in 178 (34.6%); much higher with tenecteplase than standard care (68.5% vs 39.9% within the follow-up CTA cohort; overall 23.6% vs 10.8% of randomized arms).
- Primary outcome — return to baseline mRS at 90 days — was met by 80.3% with recanalization vs 66.4% without (adjusted RR 1.21, 95% CI 1.09–1.34), consistent across mRS 0–1, mRS 0–2, and NIHSS 0 at day 5 endpoints.
- Recanalization was associated with much lower stroke progression (2.8% vs 13.1%, adjusted RR 0.21, 95% CI 0.08–0.52) and fewer SAEs (15.2% vs 28.0%, RR 0.54), without a signal of increased sICH.
- Multivariable predictors of successful recanalization: tenecteplase (OR 3.48, 95% CI 2.33–5.18), against lower odds with resolved symptoms at treatment (OR 0.50) and prior stroke (OR 0.55); age, sex, NIHSS, ASPECTS, LVO status, and comorbidities were not significant.
- Successful recanalization was itself the strongest independent predictor of NIHSS 0 at day 5/discharge (OR 3.26, 95% CI 2.12–5.01), stronger than baseline stroke severity.
- Within the successful recanalization stratum, outcomes were similar between tenecteplase and standard care arms — supporting that recanalization, not the treatment per se, drove outcomes.
- Modern medical management (dual antiplatelet therapy) achieved meaningful spontaneous recanalization (10.8% in the control arm at 4–8 hours), likely narrowing the treatment-level effect of tenecteplase seen in the parent TEMPO-2 trial.
Study Design
- Study Type
- Prespecified secondary observational cohort analysis of a randomized controlled trial (TEMPO-2)
- Randomization
- Yes
- Blinding
- PROBE — open-label with blinded end-point assessment; imaging core lab blinded to treatment and outcome
- Sample Size
- 517
- Follow-up
- 90 days (mRS up to 120 days)
- Centers
- 48
- Countries
- Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, United Kingdom
Primary Outcome
Definition: Return to baseline neurological function on modified Rankin Scale at 90 days (sliding dichotomy: mRS 0–1 if premorbid mRS 0–1; mRS 0–2 if premorbid mRS 2)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 223/336 (66.4%) unsuccessful recanalization | 143/178 (80.3%) successful recanalization | - (1.09–1.34) | <0.05 |
Limitations & Criticisms
- Post hoc, hypothesis-generating subgroup analysis of a neutral parent trial; not powered to detect small differences.
- ≈30% of patients with baseline occlusion did not undergo follow-up CTA (largely for logistical reasons — off-hours imaging, transfers), potentially introducing selection bias.
- Recanalization was measured at a single time point (4–8 hours); late spontaneous recanalization (likely facilitated by dual antiplatelet therapy) in the control arm may attenuate observed differences and cannot be captured.
- Multiple comparisons increase the risk of type I error; some associations may be due to chance.
- Did not evaluate other biological modifiers of outcome such as clot burden, collateral status, ischemia severity, or final infarct volume.
- mRS ceiling effects in this low-NIHSS population may mask small but clinically meaningful functional differences.
Citation
Stroke. Published online June 19, 2026. doi:10.1161/STROKEAHA.125.052872