The DONE SYMPLE Investigator-initiated phase III prospective, randomized, open-label, blinded endpoint-controlled clinical trial.
This clinical trial is a global clinical study testing whether a procedure called endovascular therapy, which removes blood clots from blocked brain arteries, can safely benefit more stroke patients when used up to 72 hours after symptoms begin. Endovacular Therapy is already proven to improve recovery in patients treated within 6 hours, but only when advanced imaging like Computed Tomography (CT) perfusion or Magnetic Resonance Imaging (MRI) is available to guide treatment. Unfortunately, many hospitals, specially in underserved areas, do not have access to this type of imaging.
This trial will investigate whether a basic brain scan called non-contrast CT, which is widely available in hospitals around the world, can be used instead. Special software will automatically analyze the CT scan to help doctors decide if a patient has enough brain tissue left to save with Endovascular Therapy. If this simpler approach works, it could expand access to lifesaving stroke care for more people globally.
The study will enroll 500 adult stroke patients, ages 18 to 80, with a large vessel blockage in the brain's anterior circulation, moderate to severe stroke symptoms, and who are between 6 and 72 hours from when they were last known to be well. All participants will undergo CT imaging analyzed by the automated software. If the scan shows a small core of already damaged brain tissue and a larger area of threatened but still viable brain, the patient will qualify.
Participants will be randomly assigned to receive either standard medical therapy alone or medical therapy plus Endovasculat Therapy which involves inserting a catheter through a blood vessel to reach the brain and using a device to remove the clot. This procedure is performed by trained stroke or neurointerventional specialists. The study is "open-label," meaning patients and doctors know which treatment is given, but the assessment of patient recovery will be done by independent reviewers who do not know the group assignments.
The primary goal is to determine if patients who receive Endovascular Therapy have better recovery at 90 days, measured by a scale called the modified Rankin Scale, which assesses how much disability a patient has after a stroke. The trial will also look at safety (especially brain bleeding after treatment), size and growth of brain injury on follow-up scans, recovery of strength and language, and overall quality of life and survival. Imaging will be reviewed centrally by a specialized team, and results will be analyzed to see how well Endovascular Therapy performs using this new patient selection method.
The DONE SYMPLE Trial is sponsored by Foundacio Ictus in Barcelona Spain and the University of Iowa is the Central Coordinating Center for the Study. It will take place at up to 20 hospitals worldwide. All patients will be followed closely with exams and imaging at specific time points up to 90 days after treatment.
If successful, this trial could change stroke care around the world by proving that Endovascular Therapy can be used safely and effectively even without advanced imaging, using tools available in most hospitals. This could help more stroke patients, especially in rural or resource-limited areas, access treatments that may improve their chances of recovery and reduce long-term disability.
Pre-stroke score (mRS) of 0-1 in participants aged 18 to 70 years.
Pre-stroke Modified Rankin Scale (mRS) score of 0 in participants older than 70 years.
Presenting with signs and symptoms consistent with an acute ischemic stroke within 24-72 hours from last known well. *
Baseline NIHSS ≥8.
Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test.
Known severe allergy (more than a rash) to contrast media uncontrolled by medications.
Refractory hypertension (defined as persistent systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg) despite medication.
Midline shift or herniation.
Parallel
Endovascular Therapy (Mechanical Thrombectomy)
Other interventionEndovascular therapy performed with CE-approved thrombectomy devices, initiated within 6 to 72 hours after stroke onset in patients with anterior circulation large vessel occlusion. The procedure is guided by an automated non-contrast CT detection tool and follows standard device-specific instructions for use.
Standard Medical Management
Other interventionStandard medical management including therapies such as antiplatelet agents, anticoagulants, blood pressure control, and general supportive care. Delivered in accordance with institutional guidelines for acute ischemic stroke.
Global Disability at 90 Days
Global disability will be measured using the disability-weighted modified Rankin Scale (dw-mRS) at 90 days (±14 days) post-stroke. The dw-mRS is a validated tool that captures the severity of post-stroke disability across seven levels, ranging from no symptoms (0) to death (6). This outcome evaluates whether endovascular therapy (EVT) plus medical management results in superior functional outcomes compared to medical management alone in patients with anterior circulation large vessel occlusion (LVO) strokes treated between 6-72 hours after stroke onset and selected exclusively by automated non-contrast CT imaging.
Ordinal Distribution of the Modified Rankin Scale (mRS) at 90 Days
Global disability will be assessed using the full ordinal distribution of the Modified Rankin Scale (mRS), a 7-point scale that measures functional independence and global disability after stroke. The scale ranges from 0 to 6, where 0 indicates no symptoms and 6 indicates death. Higher scores represent worse outcomes. For the purposes of this analysis, categories 5 (severe disability) and 6 (death) will be collapsed into a single category to enhance statistical robustness.
Proportion of Participants with Functional Independence (mRS 0-2) at 90 Days
Functional independence will be defined as achieving a score of 0 to 2 on the Modified Rankin Scale (mRS), a 7-point scale used to measure the degree of disability or dependence in daily activities following a stroke. The scale ranges from 0 (no symptoms) to 6 (death), with higher scores indicating worse outcomes. Scores of 0 to 2 reflect no symptoms, slight disability, or moderate disability with preserved independence.
Change in NIH Stroke Scale (NIHSS) Score at 24 Hours
Absolute change in the National Institutes of Health Stroke Scale (NIHSS) score from baseline to 24 hours post-randomization. The NIHSS is a 42-point clinical scale used to assess neurological impairment in patients with stroke. Scores range from 0 to 42, with higher scores indicating greater stroke severity and worse neurological function. A decrease in NIHSS score represents clinical improvement.
Change in NIHSS Score at Day 5 or Discharge
Absolute change in the National Institutes of Health Stroke Scale (NIHSS) score from baseline to Day 5 (±1 day) post-randomization or hospital discharge, whichever occurs first. The NIHSS is a validated clinical scale ranging from 0 (no neurological deficit) to 42 (most severe deficit), with higher scores indicating more severe stroke-related impairment. A reduction in score reflects neurological improvement.
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Santiago Ortega Gutierrez
Lead sponsor
University of Iowa
Sponsor institution
Fundació Ictus
Collaborator