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

Study Description

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.

Condition or disease	Intervention/treatment
Stroke; Stroke, Acute; Stroke, Ischemic	Procedure: Endovascular Stroke Treatment; Other: Medical Management

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 Design

• Study Type: Observational
• Estimated Enrollment: 1060 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Treatment With Endovascular Intervention for STroke Patients With Existing Disability
• Actual Study Start Date: November 16, 2023
• Estimated Primary Completion Date: January 15, 2028
• Estimated Study Completion Date: April 15, 2028

Groups and Cohorts

Group/Cohort

Intervention/treatment

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

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.

Outcome Measures

Primary Outcome Measures :

1. 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)

Secondary Outcome Measures :

1. 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
2. Return to the pre-stroke mRS level [ Time Frame: 90 (±14) days after treatment initiation ]
   Returning to the pre-stroke mRS level post stroke
3. 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)
4. 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.

Other Outcome Measures:

1. 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)
2. 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)
3. Barthel Index Scale [ Time Frame: 90 (±14) days after treatment initiation ]
   Barthel Index range: 0-100, higher scores mean participant is independent
4. 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
5. 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.
6. 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
7. Death [ Time Frame: 90 (±14) after treatment initiation ]
8. Symptomatic intracranial hemorrhage [ Time Frame: 24 (±6) hours ]
   Evaluate modified Heidelberg definition

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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)

Contacts and Locations

Contacts

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

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

Locations

United States, Arizona

HonorHealth; Not yet recruiting

Phoenix, Arizona, United States, 85013

Contact: Ashu Jadhav, MD

Principal Investigator: Ashu Jadhav, MD

United States, California

University of California at Los Angeles; Not yet recruiting

Los Angeles, California, United States, 90095

Contact: Jeffrey Saver, MD

Principal Investigator: Jeffrey Saver, MD

United States, Connecticut

Hartford Health Hospital; Not yet recruiting

Hartford, Connecticut, United States, 06106

Contact: Tapan Mehta, MD

Principal Investigator: Tapan Mehta, MD

Yale University; Not yet recruiting

New Haven, Connecticut, United States, 06510

Contact: Adam DeHavenon, MD

Principal Investigator: Adam DeHavenon, MD

United States, Florida

University of Miami; Not yet recruiting

Miami, Florida, United States, 33125

Contact: Robert Starke, MD

Principal Investigator: Robert Starke, MD

United States, New York

Icahn School of Medicine at Mount Sinai; Not yet recruiting

New York, New York, United States, 10029

Contact: J Mocco, MD

Principal Investigator: J Mocco, MD

Columbia University; Not yet recruiting

New York, New York, United States, 10032

Contact: Joshua Wiley, MD

Principal Investigator: Joshua Wiley, MD

United States, Ohio

University of Cincinnati Medical Center; Recruiting

Cincinnati, Ohio, United States, 45219

Contact: Stacie Demel, DO, PhD

Principal Investigator: Stacie Demel, DO, PhD

United States, Pennsylvania

University of Pittsburgh Medical Center; Not yet recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contact: Raul Nogueira, MD

Principal Investigator: Raul Nogueira, MD

United States, Tennessee

Vanderbilt University Medical Center; Not yet recruiting

Nashville, Tennessee, United States, 37232

Contact: Michael Froehler, MD

Principal Investigator: Michael Froehler, MD

United States, Washington

University of Washington; Not yet recruiting

Seattle, Washington, United States, 98104

Contact: David Tirschwell, MD

Principal Investigator: David Tirschwell, MD

United States, West Virginia

West Virginia University; Not yet recruiting

Morgantown, West Virginia, United States, 26506

Contact: Ansaar Rai, MD

Principal Investigator: Ansaar Rai, MD

Sponsors and Collaborators

University of Cincinnati

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

More Information

• Responsible Party: Eva A. Mistry, Assistant Professor, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT05911568
• Other Study ID Numbers: 2023-0299
• First Posted: June 22, 2023
• Last Update Posted: November 28, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

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

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

Additional relevant MeSH terms:

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