EnDOvascular Therapy for Late WiNdow IschEmic Stroke Patients Selected bY AutoMatic Plain ComputErized Tomography

NCT07001852 | Recruiting DMC

• 1 other identifier: 202312563
• Study Type: interventional
• Target: 500
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Stroke Acute

Keywords

large vessel occlusion; Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• 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.

  90 days (±14 days)

Secondary Outcomes (12)

• Ordinal Distribution of the Modified Rankin Scale (mRS) at 90 Days

  90 days (±14 days)

• Proportion of Participants with Functional Independence (mRS 0-2) at 90 Days

  90 days (±14 days)

• Change in NIH Stroke Scale (NIHSS) Score at 24 Hours

  24 hours (±16 hours)

• Change in NIHSS Score at Day 5 or Discharge

  5 days (±1 day) or at discharge

• Major Early Neurological Improvement at 24 Hours

  24 hours (±16 hours)

Study Arms (2)

Endovascular Therapy + Standard Medical Management

ACTIVE COMPARATOR

Participants in this arm will receive standard medical management for acute ischemic stroke plus endovascular therapy (mechanical thrombectomy). Treatment is initiated within 6 to 72 hours of stroke onset and is guided by automated non-contrast CT selection software.

Other: Endovascular Therapy (Mechanical Thrombectomy); Other: Standard Medical Management

Standard Medical Management Alone

ACTIVE COMPARATOR

Participants in this arm will receive standard medical management for acute ischemic stroke without undergoing endovascular therapy. Treatment decisions are made according to institutional protocols and exclude mechanical thrombectomy.

Other: Standard Medical Management

Interventions

Endovascular Therapy (Mechanical Thrombectomy) OTHER

Endovascular 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.

Endovascular Therapy + Standard Medical Management

Standard Medical Management OTHER

Standard 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.

Endovascular Therapy + Standard Medical Management; Standard Medical Management Alone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 80 years of age:
• 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.
• NCCT imaging indicating the existence of an anterior circulation LVO by an automated software, or CTA (when available).
• Core volume ≤ 70 cc determined by a deep learning algorithm in automated software and/or ASPECTS scoring ≥ 6. \*\*
• Arterial puncture within 72 hours (after the first symptoms or LKW).
• Arterial puncture within 90 minutes from initial CT.
• Ability to randomize within 72 hours after stroke onset (last seen well).
• Ability to obtain signed informed consent or subject's Legally Authorized representative (LAR) has signed Consent form \*\*\*
• Patients in the 6-24-hour after Last Known Well (LKW) may be enrolled only in centers where thrombectomy is not offered as standard of care due to the absence of advanced imaging capabilities.
• In cases of discrepancy between the automated tool LVO detection and volume, and ASPECT Score or CTA judgment or Computed Tomography Angiography CTA findings, ASPECTS and CTA will take precedence.
• If approved by local ethics committee and country regulations, the investigator is allowed to enroll a patient utilizing emergency informed consent procedures if neither the patient nor the representative or person of trust is available to sign the informed consent form. However, as soon as possible, the patient is informed, and his/her consent is requested for the possible continuation of this research.

You may not qualify if:

• 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.
• CT evidence of the following conditions:
• Midline shift or herniation.
• Evidence of intracranial hemorrhage.
• Mass effect with effacement of the ventricles.
• Bilateral strokes.
• Clot retrieval previously attempted \<6 hours.
• Treated with thrombolytics \>4.5 hours after last seen well.
• Intracranial tumors.
• Life expectancy less than 90 days prior to stroke onset.
• Participation in another randomized clinical trial that could confound the evaluation of the study.
• Presumed septic embolus, or suspicion of bacterial endocarditis.
• Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, e.g. dementia with prescribed anti-cholinesterase inhibitor (e.g. Aricept).

Sponsors & Collaborators

• Santiago Ortega Gutierrez: lead
• Fundació Ictus: collaborator

Study Sites (2)

University of Iowa

Iowa City, Iowa, 52242, United States

NOT YET RECRUITING

Erebouni Medical Center

Yerevan, Armenia

RECRUITING

Related Publications (4)

• Jovin TG, Nogueira RG, Lansberg MG, Demchuk AM, Martins SO, Mocco J, Ribo M, Jadhav AP, Ortega-Gutierrez S, Hill MD, Lima FO, Haussen DC, Brown S, Goyal M, Siddiqui AH, Heit JJ, Menon BK, Kemp S, Budzik R, Urra X, Marks MP, Costalat V, Liebeskind DS, Albers GW. Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis. Lancet. 2022 Jan 15;399(10321):249-258. doi: 10.1016/S0140-6736(21)01341-6. Epub 2021 Nov 11.

  PMID: 34774198 BACKGROUND

• Desai SM, Haussen DC, Aghaebrahim A, Al-Bayati AR, Santos R, Nogueira RG, Jovin TG, Jadhav AP. Thrombectomy 24 hours after stroke: beyond DAWN. J Neurointerv Surg. 2018 Nov;10(11):1039-1042. doi: 10.1136/neurintsurg-2018-013923. Epub 2018 May 28.

  PMID: 29807887 BACKGROUND

• Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, Sila CA, Hassan AE, Millan M, Levy EI, Mitchell P, Chen M, English JD, Shah QA, Silver FL, Pereira VM, Mehta BP, Baxter BW, Abraham MG, Cardona P, Veznedaroglu E, Hellinger FR, Feng L, Kirmani JF, Lopes DK, Jankowitz BT, Frankel MR, Costalat V, Vora NA, Yoo AJ, Malik AM, Furlan AJ, Rubiera M, Aghaebrahim A, Olivot JM, Tekle WG, Shields R, Graves T, Lewis RJ, Smith WS, Liebeskind DS, Saver JL, Jovin TG; DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4;378(1):11-21. doi: 10.1056/NEJMoa1706442. Epub 2017 Nov 11.

  PMID: 29129157 BACKGROUND

• Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.

  PMID: 25882510 BACKGROUND

MeSH Terms

Conditions

Stroke; Ischemic Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Tudor Jovin, MD

  Cooper University Health Care

  PRINCIPAL INVESTIGATOR

• Marc Ribo, MD

  Hospital Vall d"Hebron Barcelona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Santiago Ortega, MD

CONTACT

319-3845628; santy-ortega@uiowa.edu

Jorge Cespedes, MD

CONTACT

3193845628; jorge-cespedes@uiowa.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Data Analysts: Individuals analyzing the data may also be blinded to the treatment assignment to avoid bias in data interpretation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The DONE SYMPLE Trial follows a parallel assignment model, in which eligible participants are randomly assigned in a 1:1 ratio to one of two study arms: (1) standard medical therapy alone (control group), or (2) standard medical therapy plus endovascular thrombectomy (intervention group). Participants remain in their assigned group for the duration of the study, and outcomes are assessed at predefined time points. This design allows for direct comparison between the intervention and control arms to evaluate the safety and efficacy of endovascular treatment initiated between 6 and 72 hours from last known well, based on selection by non-contrast CT analyzed with automated software.

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: June 3, 2025
• Study Start: October 14, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: October 16, 2025

Record last verified: 2025-10

Locations

AR (1); US (1)