Treatment With Endovascular Intervention for STroke Patients With Existing Disability (TESTED)

• ClinicalTrials.gov Identifier: NCT05911568
• Recruitment Status: Recruiting
• First Posted: June 22, 2023
• Last Update Posted: November 28, 2023
• Sponsor: University of Cincinnati
• Collaborators: Patient-Centered Outcomes Research Institute; University of California, Los Angeles; Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Eva A. Mistry, University of Cincinnati

Tracking Information

• First Submitted Date: June 9, 2023
• First Posted Date: June 22, 2023
• Last Update Posted Date: November 28, 2023
• Actual Study Start Date: November 16, 2023
• Estimated Primary Completion Date: January 15, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 21, 2023)

modified Rankin Scale (mRS) [ Time Frame: 90 (±14) days after treatment initiation ]

Score of 0-3, 4, 5 or 6 on the modified Rankin Scale (mRS) (Note: mRS range: 0 (no residual symptoms) to 6 (death)

Original Primary Outcome Measures (submitted: June 20, 2023)

modified Rankin Scale (mRS) [ Time Frame: 90 (±14) days after treatment initiation ]

Score of 3, 4, 5 or 6 on the modified Rankin Scale (mRS) (Note: mRS range: 0 (no residual symptoms) to 6 (death)

Current Secondary Outcome Measures (submitted: July 21, 2023)

• Disability-weighted (or utility-weighted) mRS [ Time Frame: 90 (±14) days after treatment initiation ]
  Standard utility weights applied to the mRS categories as follows: 1.0 for mRS level 0; 0.91 for mRS level 1; 0.76 for mRS level 2; 0.65 for mRS level 3; 0.33 for mRS level 4; 0 for mRS level 5; and 0 for mRS level 6
• Return to the pre-stroke mRS level [ Time Frame: 90 (±14) days after treatment initiation ]
  Returning to the pre-stroke mRS level post stroke
• EQ-5D-5L [ Time Frame: 90 (±14) days after treatment initiation ]
  Quality of life assessment scale with range: 0 (worst health) to 100 (best health)
• Academic Medical Center - Linear Disability Scale (ALDS) [ Time Frame: 90 (±14) days after treatment initiation ]
  Generic item bank that measures the disability status of patients with a broad range of diseases, as expressed by the ability to perform activities in daily living.

Original Secondary Outcome Measures (submitted: June 20, 2023)

• Disability-weighted (or utility-weighted) mRS [ Time Frame: 90 (±14) days after treatment initiation ]
  Score of 3, 4, 5 or 6 on the modified Rankin Scale (mRS) (Note: mRS range: 0 (no residual symptoms) to 6 (death)
• Return to the pre-stroke mRS level [ Time Frame: 90 (±14) days after treatment initiation ]
  Score of 3, 4, 5 or 6 on the modified Rankin Scale (mRS) (Note: mRS range: 0 (no residual symptoms) to 6 (death)
• EQ-5D-5L [ Time Frame: 90 (±14) days after treatment initiation ]
  EQ-5D-5L (Scale range: 0 (worst health) to 100 (best health)
• Academic Medical Center - Linear Disability Scale (ALDS) [ Time Frame: 90 (±14) days after treatment initiation ]
  he Academic Medical Center Linear Disability Score (ALDS) is a recently developed generic item bank that measures the disability status of patients with a broad range of diseases, as expressed by the ability to perform activities in daily living.

Current Other Pre-specified Outcome Measures (submitted: July 21, 2023)

• modified Rankin Scale (mRS) [ Time Frame: At hospital discharge ]
  Score of 0-3, 4, 5 or 6 on the modified Rankin Scale (mRS) (Note: mRS range: 0 (no residual symptoms) to 6 (death)
• Montreal Cognitive Assessment (MoCA) [ Time Frame: 90 (±14) days after treatment initiation ]
  Montreal Cognitive Assessment (MoCA) (Note: MoCA range: 0-30, higher scores mean better outcome)
• Barthel Index Scale [ Time Frame: 90 (±14) days after treatment initiation ]
  Barthel Index range: 0-100, higher scores mean participant is independent
• Initial residence level or better time during first 90 days post-stroke [ Time Frame: 90 days after treatment initiation ]
  Number of days spend at the initial residence level or better during the first 90 days post-stroke
• Zarit's Burden Interview (ZBI) [ Time Frame: 90 (±14) days after treatment initiation ]
  ZBI is a measure of caregiving burden that includes a 22 item interview. Each item on the interview is a statement which the caregiver is asked to endorse using a 5-point scale. Response options range from 0 (Never) to 4 (Nearly Always). We will use the 4 item version of the ZBI which has good correlation with the full version.
• Extended Thrombolysis in Cerebral Ischemia scale [ Time Frame: At the end of EVT procedure ]
  The 7-point scale of eTICI is as follows: eTICI0 = 0% reperfusion; eTICI 1 = minimal flow past the occlusion but no perfusion ; eTICI2a = 1-49% reperfusion; eTICI2b50 = 50-66% reperfusion; eTICI2b67 = 67-89% reperfusion; eTICI2c = 90-99% reperfusion; eTICI3 = complete reperfusion
• Death [ Time Frame: 90 (±14) after treatment initiation ]
• Symptomatic intracranial hemorrhage [ Time Frame: 24 (±6) hours ]
  Evaluate modified Heidelberg definition

Original Other Pre-specified Outcome Measures (submitted: June 20, 2023)

• modified Rankin Scale (mRS) [ Time Frame: 7 (±2) after treatment initiation ]
  Score of 3, 4, 5 or 6 on the modified Rankin Scale (mRS) (Note: mRS range: 0 (no residual symptoms) to 6 (death)
• Montreal Cognitive Assessment (MoCA) [ Time Frame: 90 (±14) days after treatment initiation ]
  Montreal Cognitive Assessment (MoCA) (Note: MoCA range: 0-30, higher scores mean better outcome)
• Barthel Index Scale [ Time Frame: 90 (±14) days after treatment initiation ]
  Barthel Index Scale (Note: Barthel Index range: 0-100, higher scores mean participant is independent)
• Home-time during first 90 days post-stroke [ Time Frame: 90 days after treatment initiation ]
  Score of 3, 4, 5 or 6 on the modified Rankin Scale (mRS)
• Initial residence level or better time during first 90 days post-stroke [ Time Frame: 90 days after treatment initiation ]
  Number of days spend at the initial residence level or better during the first 90 days post-stroke
• Zarit's Burden Interview (ZBI) [ Time Frame: 90 (±14) days after treatment initiation ]
  ZBI is a measure of caregiving burden that includes a 22 item interview. Each item on the interview is a statement which the caregiver is asked to endorse using a 5-point scale. Response options range from 0 (Never) to 4 (Nearly Always)
• Extended Thrombolysis in Cerebral Ischemia scale [ Time Frame: At the end of EVT procedure ]
  The 7-point scale of eTICI is as follows: eTICI0 = 0% reperfusion; eTICI 1 = minimal flow past the occlusion but no perfusion ; eTICI2a = 1-49% reperfusion; eTICI2b50 = 50-66% reperfusion; eTICI2b67 = 67-89% reperfusion; eTICI2c = 90-99% reperfusion; eTICI3 = complete reperfusion
• Death [ Time Frame: 90 (±14) after treatment initiation ]
• Symptomatic intracranial hemorrhage [ Time Frame: 24 (±6) hours ]
  Evaluate modified Heidelberg definition

Descriptive Information

• Brief Title: Treatment With Endovascular Intervention for STroke Patients With Existing Disability
• Official Title: Treatment With Endovascular Intervention for STroke Patients With Existing Disability
• Brief Summary: TESTED will compare the risks and benefits of endovascular thrombectomy (EVT) to medical management (no EVT) in ischemic stroke patients who have a blockage in one of the large blood vessels in the brain and have a moderate-to-severe disability prior to their stroke.

Detailed Description

People with disabilities can suffer acute ischemic stroke (AIS). Endovascular clot removal is a breakthrough therapy for large vessel occlusion (LVO) AIS. Pre-stroke disabled patients were excluded from pivotal EVT stroke trials, so whether EVT is effective for those with pre-stroke disability is not known. As a result, two competing, widely-practiced, treatment paradigms have emerged based on individual practitioners' extrapolation of EVT benefits and safety from patients without a pre-stroke disability to those with disability: 1) Multimodal Medical Management (MMM; using intravenous thrombolysis, antiplatelets, anti-hypertensives, cholesterol lowering medications, and other rehabilitative measures, as indicated) without EVT, and 2) EVT with the background of MMM.

TESTED will enroll patients with LVO-AIS who have a pre-existing disability, defined as pre-stroke modified Rankin score (mRS) 3 and 4, at 12 geographically distinct comprehensive stroke centers serving diverse race-ethnic and socioeconomic populations. The central objective of TESTED is to determine the comparative effectiveness and safety of these two different practice paradigms.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Ischemic stroke patients who have a blockage in one of the large blood vessels in the brain and have a moderate-to-severe disability prior to their stroke. They will be consented up to 72 hours after stroke onset in the acute hospitalization setting.

Condition

• Stroke
• Stroke, Acute
• Stroke, Ischemic

Intervention

• Procedure: Endovascular Stroke Treatment
  Patients who receive endovascular stroke treatment when they are admitted into the hospital, as determined by their clinical care team. Endovascular stroke treatment consist of catheter-based treatment for the blood clot causing the acute ischemic stroke
• Other: Medical Management
  Patients who receive MMM when they are admitted into the hospital, as determined by their clinical care team. MMM may involve any combination of the following: intravenous thrombolysis, antiplatelets, anti-hypertensives, cholesterol-lowering medications, and rehabilitative care. Specifically, this treatment does not involve endovascular stroke treatment.

Study Groups/Cohorts

Stroke patients with moderate-to-severe pre-stroke disability

Patients with pre-stroke modified Rankin scale score 3 or 4, presenting with a anterior circulation large vessel occlusion stroke within 24 hours of last known well

Interventions:

• Procedure: Endovascular Stroke Treatment
• Other: Medical Management

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 20, 2023): 1060
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 15, 2028
• Estimated Primary Completion Date: January 15, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adult patients (≥18 years)
2. Moderate-to-severe pre-stroke functional disability, defined as mRS 3-4, for at least 3 months prior to stroke onset
3. Presenting to study hospital within 24 hours of last known well time
4. Diagnosis of acute ischemic stroke
5. Intracranial causative occlusion of the internal carotid artery or the M1 or dominant M2 segments of the middle cerebral artery visualized on the baseline CT(or MR) angiogram
6. Presenting CT Alberta Stroke Program Early CT (ASPECT) score ≥3 or MRI ASPECT score ≥4
7. Presenting NIH Stroke Scale score ≥6
8. Informed consent from patient if competent or from legally authorized representative

Exclusion Criteria:

1. Known diagnosis of a terminal cancer or terminal illness at the time of stroke
2. Assessment of pre-stroke functional status cannot be performed during the hospital stay
3. Pre-stroke disability deemed temporary in the investigator's opinion (for example, recovering from a general medical illness or traumatic bodily injury)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Eva Mistry, MD; 513-558-1291; mistryea@ucmail.uc.edu

Contact: Naima Griffin; 513-558-0125; griffna@ucmail.uc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05911568
• Other Study ID Numbers: 2023-0299
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: One year after completing of the final analysis

• Current Responsible Party: Eva A. Mistry, University of Cincinnati
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Cincinnati
• Original Study Sponsor: Same as current

Collaborators

• Patient-Centered Outcomes Research Institute
• University of California, Los Angeles
• Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Eva Mistry, MD; University of Cincinnati
• Principal Investigator: Jeffrey Saver, MD; Ronald Reagan UCLA Medical Center
• Principal Investigator: J Mocco, MD; Icahn School of Medicine at Mount Sinai
• Principal Investigator: Heidi Sucharew, PhD; University of Cincinnati

• PRS Account: University of Cincinnati
• Verification Date: November 2023