CHAMGAP
APPROVEDReviewed and approved by the Chamgap Editorial Team (2026-08-18). The draft was written by AI, the existence of all 1 cited sources was verified at the original page, and the verdict passed blind grading and adversarial audit. Methodology v0.7.
Verdict No. 2771 · Search date 2026-08-18 · Methodology v0.7

MRI-selected alteplase,
does it really help with Increased functional independence at 90 days after acute ischemic stroke of unknown onset?

30-Second Summary
B
Evidence Grade B · 70 · Safety warning
MRI-selected alteplase increased functional independence after ischemic stroke of unknown onset
Alteplase can cause symptomatic or fatal intracranial and systemic bleeding; hemorrhage and death were numerically higher in this trial. It requires emergency imaging, contraindication review, and specialist stroke care.
What the
research shows
The grade is B. WAKE-UP randomized 503 patients with an acute DWI lesion but no corresponding FLAIR hyperintensity. Observed 90-day mRS 0-1 occurred in 131/246 (53.3%) with alteplase versus 102/244 (41.8%) with placebo, an 11.5-point absolute difference; adjusted OR 1.61 (95% CI 1.09-2.36). It remains one confirmatory trial stopped at 503 rather than 800 because EU funding was ending, giving B with 70 points.
What the
ads claim
The result does not mean every stroke noticed on awakening should receive thrombolysis. It applies after specialist confirmation of no hemorrhage, a DWI lesion without corresponding FLAIR hyperintensity, thrombolysis eligibility, and the thrombectomy pathway.
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Useful facts when choosing a product

  • Alteplase was dosed at 0.9 mg/kg, with 10% as a bolus and the remainder infused over 60 minutes.
  • MRI was both an eligibility tool and an assessment tool; company supply was not reported.
  • WAKE-UP is an MRI-selected stroke thrombolysis trial, not the PRAMI myocardial-infarction PCI trial.
Gap Measurement · Verdict 2771 · B 70
What advertising claims
What independent, higher-quality research supports
△ GAP
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What the research actually shows

Sixty-one centers in eight European countries assigned 254 and 249 patients through a web-based permuted-block procedure and used matching placebo under double masking. The primary efficacy population was, in the article's words, ‘the intention-to-treat population, which included all the patients who had undergone randomization,’ all 503 patients. Outcomes were observed in 490, 246 versus 244, but ‘Missing data in the primary outcome analysis were imputed with the use of multiple imputation techniques,’ so 13 were not discarded. Enrollment stopped at 503 of a planned 800 because EU funding was expected to cease, ‘without an interim analysis of trial data.’ This was early stopping for resource limitations, not a prespecified efficacy or harm boundary and not termination after an unplanned interim analysis. EU FP7 grant 278276 funded the trial, and the article states, ‘There was no industry funding or involvement in any aspect of the trial.’ Author company relationships were disclosed, but company supply of alteplase, placebo, or MRI assessment tools was not reported.

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Why this is classified as B (70)

A publicly funded double-blind placebo-controlled trial found a large functional benefit, but lack of independent replication and early stopping when funding ended give B with 70 points.

Counterpoint. B does not mean the observed benefit was small. It reflects uncertainty from one early-stopped trial and imprecise harm estimates.

Rejudgment record. Cross-check applied — Cross-checked WAKE-UP's 503-person intention-to-treat analysis, multiple imputation, MRI-selected functional endpoint, public funding, and resource-driven early stopping

Scoring profile behind this grade
EndpointPPatient-reported treatment goal - the symptom is the goal
ReplicationR1Single confirmatory trial
IndependenceI2Decisive evidence is publicly or non-profit funded
Effect sizeE+Meets the clinically important threshold

The scoring table and the verdict agree (B).

Sub-claim grades by effect

This ingredient is marketed for several effects. A single overall grade blends strong and weak claims together, so each effect is graded separately here. The overall grade reflects the strongest disconfirming or core claim.

Effect (sub-claim)GradeBasis
Increased functional independence at 90 daysBThe observed absolute difference was 11.5 points and the adjusted intention-to-treat OR was 1.61.
Applicability to every stroke of unknown onset?The trial required a specific DWI-FLAIR mismatch and thrombolysis eligibility.

Cross-check — Codex and Claude

This verdict was drafted by Codex through literature review and source-existence checks, cross-checked through blind grading and adversarial audit, and settled by reapplying the methodology boundary rules. Cases with split grades were resolved through rejudgment.
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Evidence Table

StudyDesignSampleFundingEndpointResultWeight
Study 1Multicenter double-blind placebo-controlled superiority randomized trial13EU Seventh Framework Programme grant 278276; no industry funding or involvementmRS 0-1 at 90 daysObserved 53.3% versus 41.8%, absolute difference +11.5 points; adjusted OR 1.61 (95% CI 1.09-2.36), P=.02Single publicly funded confirmatory trial stopped early for resource limitations
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Receipt — 1 References

All 1 cited sources were verified for existence at the original page (as of 2026-08-18).

Thomalla G, Simonsen CZ, Boutitie F, et al.; WAKE-UP Investigators. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018;379(7):611-622. PMID: 29766770. DOI: 10.1056/NEJMoa1804355. NCT01525290.
checked
Draft and rewrite: Codex (AI) · Verification: Codex blind grading and adversarial audit · Final adjudication: Claude
Reviewed and approved: Chamgap Editorial Team · Approval date: 2026-08-18 · Corrections: none

Cite this verdict

MRI-selected alteplase x functional independence after stroke of unknown onset Evidence Grade B card
[Chamgap] MRI-selected alteplase x functional independence after stroke of unknown onset — Evidence Grade B·70. 1 cited sources checked. Source: https://chamgap.com/en/verdicts/heart/mri-selected-alteplase-unknown-onset-ischemic-stroke-functional-independence/ · CC BY 4.0

CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.

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What this document does and does not do

Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.