Endovascular clot-removal guided by automated standard CT for late-window ischemic stroke

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

This trial will test whether removing clots with endovascular therapy guided only by automated non-contrast CT can help adults with large-vessel ischemic stroke treated 6–72 hours after symptoms begin.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 500 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: University of Iowa (Academic / other)
• Locations: 2 sites (Iowa City, Iowa and 1 other locations)
• Trial ID: NCT07001852 on ClinicalTrials.gov

What this trial studies

The DONE SYMPLE Trial is a phase III, multicenter, randomized, open-label trial with blinded endpoint assessment that will enroll 500 patients with anterior circulation large-vessel occlusion treated 6–72 hours after last known well. Participants are randomized 1:1 to standard medical therapy alone or endovascular thrombectomy plus standard therapy, with stratification by baseline NIH Stroke Scale, time from onset, core infarct volume, and enrolling site. Patient selection relies solely on automated analysis of non-contrast CT to detect vessel occlusion and estimate ischemic core (≤70 cc or ASPECTS ≥6), enabling enrollment at centers without perfusion or MRI capability. Endovascular procedures use approved thrombectomy devices and outcomes are adjudicated blinded to treatment allocation.

Who should consider this trial

Good fit: Adults 18–80 years old with anterior circulation large-vessel ischemic stroke, NIHSS ≥8, presenting 6–72 hours after last known well, with automated NCCT showing core ≤70 cc or ASPECTS ≥6 and who can undergo arterial puncture within 90 minutes of the initial CT are ideal candidates.

Not a fit: Patients with very large established infarcts (core >70 cc), posterior circulation strokes, significant pre-stroke disability outside the allowed mRS range, inability to be randomized or to undergo timely arterial puncture/imaging are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, more patients—especially those at hospitals without advanced perfusion or MRI—could safely receive clot-removal therapy and have better chances of recovery after late-window stroke.

How similar studies have performed: Pivotal late-window thrombectomy trials (DAWN, DEFUSE-3) showed benefit when advanced perfusion or MRI selection was used, but using automated non-contrast CT alone for 6–72 hour selection is a novel approach with limited prior evidence.

Eligibility criteria

Inclusion Criteria:

1. 18 to 80 years of age:

   1. Pre-stroke score (mRS) of 0-1 in participants aged 18 to 70 years.
   2. Pre-stroke Modified Rankin Scale (mRS) score of 0 in participants older than 70 years.
2. Presenting with signs and symptoms consistent with an acute ischemic stroke within 24-72 hours from last known well. \*
3. Baseline NIHSS ≥8.
4. NCCT imaging indicating the existence of an anterior circulation LVO by an automated software, or CTA (when available).
5. Core volume ≤ 70 cc determined by a deep learning algorithm in automated software and/or ASPECTS scoring ≥ 6. \*\*
6. Arterial puncture within 72 hours (after the first symptoms or LKW).
7. Arterial puncture within 90 minutes from initial CT.
8. Ability to randomize within 72 hours after stroke onset (last seen well).
9. 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.

Exclusion Criteria:

1. Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test.
2. Known severe allergy (more than a rash) to contrast media uncontrolled by medications.
3. Refractory hypertension (defined as persistent systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg) despite medication.
4. CT evidence of the following conditions:

   * Midline shift or herniation.
   * Evidence of intracranial hemorrhage.
   * Mass effect with effacement of the ventricles.
5. Bilateral strokes.
6. Clot retrieval previously attempted \<6 hours.
7. Treated with thrombolytics \>4.5 hours after last seen well.
8. Intracranial tumors.
9. Life expectancy less than 90 days prior to stroke onset.
10. Participation in another randomized clinical trial that could confound the evaluation of the study.
11. Presumed septic embolus, or suspicion of bacterial endocarditis.
12. 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).
13. Any other condition (in the opinion of the site investigator) that precludes an endovascular procedure or poses a significant hazard to the patient if an endovascular procedure was performed.

Where this trial is running

Iowa City, Iowa and 1 other locations

• University of Iowa — Iowa City, Iowa, United States (Not_yet_recruiting)
• Erebouni Medical Center — Yerevan, Armenia (Recruiting)

Study contacts

• Principal investigator: Tudor Jovin, MD — Cooper University Health Care
• Study coordinator: Santiago Ortega, MD

Conditions Stroke Acute; large vessel occlusion; Acute Ischemic Stroke