Zhou Y, He Y, Campbell BCV, et al. Alteplase for Acute Ischemic Stroke at 4.5 to 24 Hours: The HOPE Randomized Clinical Trial.
IV thrombolysis has been locked to a 4.5-hour clock since ECASS III. HOPE asks whether the clock is the right gate at all.
Alteplase within 4.5 hours of stroke onset has been standard of care since NINDS and ECASS III. But most stroke patients present outside that window, and until recently the field's answer for late presenters was almost entirely mechanical thrombectomy for large-vessel occlusions — leaving patients with smaller-vessel or distal occlusions, or those without LVO at all, without a reperfusion option once the clock ran out. HOPE is the first trial testing whether tissue viability on CT perfusion, rather than time since onset, should be the actual gate for IV thrombolysis, out to 24 hours.
| Design | Prospective, multicenter (26 centers, China), randomized, open-label, blinded-endpoint, phase III |
| Population | 372 adults with acute ischemic stroke, 4.5–24h from onset (or midpoint of last-known-well/symptom recognition for unclear-onset and wake-up strokes), no initial plan for thrombectomy |
| Imaging gate | CT perfusion: ischemic core ≤70 mL, penumbra ≥10 mL, mismatch ratio ≥20% |
| Intervention | IV alteplase + standard therapy vs. standard therapy alone (1:1) |
| Primary outcome | Modified Rankin Scale 0–1 (functionally independent, non-disabled) at 90 days |
| Baseline | Median age 72; 43% women; median NIHSS 10; median ASPECTS 9 |
Notably, HOPE did not restrict enrollment to large-vessel occlusions the way the tenecteplase trials in this window (TIMELESS, TRACE-III) did — it included distal and non-LVO strokes too, which is part of why its population and generalizability differ from those trials.
| Outcome | Alteplase | Standard care |
|---|---|---|
| mRS 0–1 at 90 days | 75/186 (40%) | 49/186 (26%) |
Alteplase increased functional independence by an absolute 14 percentage points. It also increased symptomatic intracranial hemorrhage relative to standard care — the expected cost of thrombolysis in any window. Critically, that increase in sICH did not translate into a mortality difference between arms. That combination (more sICH, same mortality, better functional outcome) is the entire clinical argument for the trial.
This isn't the first late-window thrombolysis data — it's the first with alteplase, and the first not restricted to LVO.
TIMELESS and TRACE-III both tested IV tenecteplase 4.5–24h after onset in patients with large-vessel occlusion and showed the approach was safe, but their efficacy signal was inconsistent — and post hoc analysis suggested a substantial share of the TIMELESS benefit may have come from patients who went on to rapid thrombectomy anyway, muddying attribution to the lytic itself. HOPE adds two things those trials didn't have: an alteplase-specific (not tenecteplase) dataset in this window, and inclusion of patients regardless of LVO status, including distal occlusions.
Single-country, single-drug-class, and a control arm that wasn't blinded to treatment status.
The RebelEM summary is accurate on every number that matters: functional independence roughly 1.5× more likely with alteplase, more sICH, no mortality penalty. The clinically important framing underneath those numbers is that HOPE supports a "tissue over time" model — using CT perfusion to identify patients with salvageable brain regardless of the clock — as a genuinely viable alternative gate for thrombolysis, not just for thrombectomy. It is not yet practice-changing outside a research or perfusion-imaging-capable setting: the population is single-country, the comparison to tenecteplase in the same window is still open, and the imaging thresholds haven't been independently validated.