Stroke Care Beyond 4.5 Hours: Trial Tests Simpler CT Screening
When it comes to strokes, time is everything. The faster blood flow is restored to the brain during an ischemic stroke, the greater the chances of minimizing damage and preserving function. This is why the phrase "time is brain" has long been a cardinal rule in emergency neurology.
In real life, however, many patients arrive at the hospital past the classic window for intravenous thrombolysis. Some wake up with symptoms, some are alone at home, and others do not immediately realize that arm weakness, facial drooping, or slurred speech could indicate a stroke.
A new clinical trial is launching in China to test a simpler approach to selecting these late-arriving patients. The study, named PEARL-SIMPLIFIED, is registered on ICH GCP under the identifier NCT07606807.
What exactly will be tested?
PEARL-SIMPLIFIED is a multicenter, randomized controlled, open-label, blinded-endpoint Phase 3 trial. The study plans to enroll 750 adult patients suffering from an acute anterior circulation ischemic stroke.
- The critical factor is the time window: participants must be admitted between 4.5 and 24 hours from symptom onset or from the time they were last known to be well.
- This inclusion covers "wake-up strokes" and strokes with an undetermined exact time of onset.
- Patients will be selected using simplified criteria based solely on a non-contrast CT scan.
- Participants will be randomly assigned into two groups: one receiving intravenous tenecteplase, and the other receiving standard medical therapy.
Why a simple CT scan is a game-changer
In the extended time window, doctors typically need to determine if there is still salvageable brain tissue and assess the risk of hemorrhage. To do this, many current protocols rely on advanced imaging techniques like CT perfusion or MRI.
However, these advanced technologies are not available in every hospital, particularly in smaller centers or resource-limited regions. A standard non-contrast CT is much faster and more widely accessible. If it proves safe to select certain patients for treatment using only a basic CT, it could revolutionize stroke care in areas lacking advanced imaging infrastructure.
What we know about tenecteplase
Tenecteplase is a thrombolytic (clot-busting) drug. The 2026 update from the AHA/ASA supports intravenous thrombolysis within 4.5 hours for eligible patients. The guidelines also recognize tenecteplase as a viable alternative to alteplase within this standard window.
Recently, JAMA published data regarding tenecteplase use in the 4.5–24 hour window, but patient selection in that context relied on perfusion imaging. The PEARL-SIMPLIFIED trial distinguishes itself by testing this treatment based exclusively on simple non-contrast CT screening.
What we cannot claim yet
It is premature to claim that tenecteplase is safe and effective for all stroke patients in the 4.5–24 hour window. Likewise, it cannot be asserted that a standard CT scan is already a proven substitute for advanced imaging in these late-stage medical decisions.
The trial will rigorously evaluate functional outcomes and safety profiles, as thrombolysis inherently carries bleeding risks. PEARL-SIMPLIFIED aims to determine whether late thrombolysis patient selection can be simplified, but standard clinical practice will not change until the Phase 3 results are published and peer-reviewed.
