A Large-Scale Clinical Trial to Improve Stroke Care, from Local Hospitals to Specialized Centers

During an ischemic stroke, a clot blocks a cerebral artery, depriving part of the brain of oxygen. Every stroke must be treated as an emergency because the more time that passes, the greater the risk of irreversible damage. To restore blood flow, doctors have two treatment options: 1) intravenous thrombolysis, which aims to dissolve the clot using medication. It has the advantage of being available in all French hospitals, but is not very effective on large clots. 2) mechanical thrombectomy, reserved for severe strokes, involves directly removing the clot from the artery. It is successful in 90% of cases, but only about 40 of the roughly 150 French facilities that treat strokes are capable of performing it. 

Typically, patients are initially referred to a local hospital, where they can receive thrombolysis, and those who require a thrombectomy must then be transferred to a specialized center, which delays treatment accordingly. 

In France, more than half of the patients treated with mechanical thrombectomy required inter-hospital transfer. 

Thrombolysis has been shown to be effective when administered within 4 hours and 30 minutes of symptom onset. However, about one in three patients arrives at the hospital after this time frame, particularly when the stroke occurs during sleep or when the emergency is reported late. We have no evidence that thrombolysis is beneficial in patients with severe stroke treated more than 4 hours and 30 minutes after symptom onset, and this is the question that TIMELESS-TNT seeks to answer.

For patients who have suffered a severe stroke and received delayed care, TIMELESS-TNT aims to determine whether the waiting time between the local hospital and the specialized center capable of performing thrombectomy (approximately 2 hours and 30 minutes on average) can be used to treat the clot sooner. The study will evaluate the benefits of intravenous thrombolysis with tenecteplase to reopen the artery before arrival at the specialized center. Preliminary observational data suggest that approximately 20% of patients treated with thrombolysis could have their artery reopened even before arriving at the specialized center, resulting in a significant reduction in neurological sequelae. However, these results must be confirmed to determine whether this strategy actually improves patient recovery while assessing its safety, particularly the risk of bleeding.

This Phase III clinical trial will include 592 adults who have suffered a severe ischemic stroke caused by the blockage of a large artery in the brain and requiring transfer to a specialized center for thrombectomy. When the exact time of the stroke is unknown—particularly for strokes that occur during sleep—the time to treatment is calculated from the last time the patient was seen without symptoms. Participants will be randomly assigned to two groups: one will receive standard of care; the other will additionally receive a dose of intravenous tenecteplase prior to transfer. In all cases, patients will be transferred to the specialized center when thrombectomy is indicated. The primary objective will be to compare patients’ recovery and level of independence at three months. The study will also assess whether the artery has recanalized before arrival at the specialized center, the need for thrombectomy, and the safety of the treatment. Recruitment is scheduled to take place over three years. The study is scheduled to begin in early 2027.

TIMELESS-TNT addresses a second challenge: increasing the involvement of non-university hospitals in clinical stroke research. Currently largely concentrated in university hospitals, clinical research involves general hospitals to a lesser extent, even though they treat a significant proportion of patients. Involving them will make it possible to open trials to more patients, better incorporate the diversity of populations and regions, and create a network that can be mobilized for future research. 

For TIMELESS-TNT, their participation is essential: it is these community hospitals that will admit and enroll patients prior to their transfer. Approximately 40 will participate in the project alongside 15 university centers. They will work in pairs, with the most experienced units supporting the community-based units in training and research implementation. StrokeLink will play a key role in this organization by mobilizing the centers and facilitating their collaboration with specialized institutions. The goal is to establish a sustainable framework that will enable these hospitals to participate in other trials.

Strokes are sometimes treated too late, particularly because some patients wait to see if their symptoms will subside or go away. However, when a stroke occurs, it is essential to act immediately. The main warning signs include facial asymmetry, such as one side drooping, weakness, paralysis, or loss of sensation in an arm, a leg, or an entire side of the body, or sudden difficulty speaking, articulating, or finding the right words. These symptoms may appear alone or simultaneously. If you notice any of these signs, call 15 immediately and do not go to the emergency room on your own: calling 15 ensures that the patient is quickly directed to the facility best equipped to treat a stroke.

7,000 to 8,000 thrombectomies are performed each year in France • 592 patients, more than 50 hospitals, including 15 university centers and approximately 40 community-based units, will participate in the study • The study involves patients with severe stroke who arrive at the hospital between 4:30 a.m. and 24 hours after the onset of the stroke • 3 years of recruitment