Clinical Trials for Stroke

Clinical Trials for Stroke Prevention, Treatment and Recovery
The UCSD Comprehensive Stroke Center has a long history leading and participating in clinical stroke trials. Since the program's inception in the mid-1980s, we have participated in over 80 clinical trials in stroke. The UCSD Stroke Team played a pivotal role in the NINDS tPA Stroke Trial (1994), which led to the first approved treatment for ischemic stroke, tPA. In 2018 we were part of the DEFUSE 3 Study, which in concert with other neurovascular embolectomy stroke studies, demonstrated the successful and safe removal of large vessel clots in stroke victims who presented to the ED within 24 hours of stroke symptom onset. As a clinical and research center, we have remained committed to pioneering new techniques and treatments to reduce stroke risk, prevent secondary stroke events, salvage brain tissue acutely, and investigate solutions to repair and recover injured brain. 

UCSD Comprehensive Stroke Center as a National and Regional Leader in Research
NIH SPOTRIAS Network: In the 2000's, the National Institute of Neurologic Disorders and Stroke (NINDS) selected nine institutions across the United States with a strong commitment to the rapid treatment of acute stroke patients who had a demonstrated collaboration between emergency medical services, emergency physicians, neurologists, and radiologists to participate in the Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS). UCSD was one of the nine centers designated. The aim of SPOTRIAS was to reduce disability and mortality in acute stroke patients through the development of improved treatment by laboratory investigation into the biology of stroke, clinical investigation of new therapies based on these laboratory studies, and assessment of outcome and improved application of effective therapies.

NIH StrokeNet Network: More recently, the NIH created the StrokeNet Network to conduct small and large clinical trials and research studies to advance acute stroke treatment, stroke prevention, and recovery and rehabilitation following a stroke. This network of 25 regional coordinating centers (RCCs) across the U.S., involves more than 200 hospitals, and is designed to serve as the infrastructure and pipeline for exciting new potential treatments for patients with stroke and those at risk for stroke. UCSD again was selected as one of initial regional centers to promote and conduct high quality stroke trials by organizing collaborating institutions in the greater San Diego region. Through this grant and the support from NIH, we were able to build a strong regional network of medical centers across our region and beyond to allow many more patients to be offered the opportunity to particpiate in state-of-the-art clinical research projects related to stroke treatment, recovery and prevention.

Current Clinical Research Studies:

ARCADIA: AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke

Study Sponsor:  National Institutes of Health (NIH) - National Institute for Neurologic Disorders and Stroke (NINDS) / StrokeNet / Columbia University
Site Principal Investigator: Royya Modir, MD (UCSD Health System La Jolla and Hillcrest, VAMC, Scripps Mercy)
Study Period:   April 2018 – Present (UCSD)

ARCADIA is a multicenter, biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial of apixaban versus aspirin in patients who have evidence of atrial cardiopathy and a recent stroke of unknown cause. Eleven hundred subjects will be recruited over 2.5 years at 120 sites in the NIH StrokeNet consortium. Subjects will be followed for a minimum of 1.5 years and a maximum of 4 years for the primary efficacy outcome of recurrent stroke and the primary safety outcomes of symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage.

In one-third of ischemic strokes, a specific cause cannot be identified. Many of these cryptogenic strokes appear to arise from a distant embolic source. Recent evidence suggests that some cryptogenic strokes may arise from left atrial thromboembolism that goes unrecognized because it has not manifested with atrial fibrillation/flutter (AF). 

This study is evaluating whether patients with some markers (signs or indications) of atrial cardiopathy and do not have atrial fibrillation/flutter, may be at risk of having an ischemic stroke before atrial fibrillation develops.

The three markers of atrial cardiopathy being tested in this study are an:

  • enlarged left atrium, a chamber of the heart;
  • elevated blood test called NT-proBNP; and
  • abnormality of the P wave on the electrocardiogram, an indication of abnormal electrical activity of the heart. 

The purpose of this research study is to compare the effects of apixaban with the effects of aspirin in patients with unexplained strokes and atrial cardiopathy to see which is better at prevention of future strokes.

For more information, please see the ClinicalTrials.gov website:
https://clinicaltrials.gov/ct2/show/NCT03192215

STRONG: Genetic Variation, Stress, and Functional Outcomes after Stroke Rehabilitation

Study Sponsor: National Institutes of Health (NIH) – National Institute of Nursing Research / University of California, Irvine
Site Principal Investigator: Kunal Agrawal, MD (UCSD)
Study Period:   January 2018 – Present

Stroke is the leading cause of long-term disability in Americans. Rehabilitation therapy is provided as standard of care following stroke, as strong evidence supports that it can help patients return to independent living. However, many patients respond differently to post-stroke rehabilitation therapy. While a number of factors have been identified that help explain some differences in treatment success among patients, overall knowledge remains limited. The STRONG study examines how stress and specific genes are related to the response to rehabilitation therapy. This approach may provide insight into biological factors that influence differences in stroke recovery, and so may help individualize rehabilitation care.

There will be approximately 1,250 participants at all sites. Individual patient participation will be 12 months.

Recently Completed Clinical Research Studies: 

POINT: Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial 

Study Sponsor:  National Institutes of Health (NIH) - National Institute for Neurologic Disorders and Stroke (NINDS).
Site Principal Investigator: Dawn Meyer, PhD, FNP-C (UCSD Hillcrest and Thornton)
Site Principal Investigator: Royya Modir, MD (Scripps Mercy)
Study Period:   September 2011 – February 2018  (UCSD) – CLOSED to Enrollment
Study Period:   April 2016 – February 2018 (Scripps Mercy) – CLOSED to Enrollment

The POINT study seeks to determine the safety and effectiveness of the combination of low-dose aspirin and a medication called clopidogrel (also known by the brand name Plavix®) in reducing the risk of stroke, heart attacks and other complications in patients who have just had a minor ischemic stroke (lack of blood flow and oxygen to the brain usually caused by a blood clot) or a transient ischemic attack (TIA) (a condition that produces stroke-like symptoms such as sudden weakness on one side of the body or trouble speaking, but the symptoms are temporary lasting up to 12 hours).  Participants will be given a one-time large dose of clopidogrel 600mg (day 1) followed by clopidogrel 75 mg/day by mouth (day 2-90) versus placebo (day 1-90).  All patients will take aspirin every day.

Several studies that tested the combination of clopidogrel and aspirin have suggested that taking these two medications together may protect patients even more from major stroke and heart attack after a TIA or minor stroke, in comparison to taking aspirin alone, but these studies were small and the risk of bleeding was increased.There will be approximately 5840 participants enrolled in about 350 hospitals internationally over 9 years. The total duration of this study is approximately 90 days for each patient. 

Patients are most often identified for this study after presenting to the Emergency Department and being diagnosed with a TIA or minor stroke. 

For more information, please see the ClinicalTrials.gov website:
https://clinicaltrials.gov/ct2/show/NCT00991029

Abstract Publication

RESPECT – ESUS: Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the  Oral Thrombin Inhibitor Dabigatran Etexilate (110 Mg Or 150 Mg, Oral B.I.D.) Versus Acetylsalicylic Acid (100 Mg Oral Q.D.) in Patients with Embolic Stroke of Undetermined Source

Study Sponsor: Boehringer Ingelheim
Site Principal Investigator: Royya Modir, MD (UCSD)
Study Period:   April 2016 – August 2018 – CLOSED to Enrollment

RESPECT ESUS is a phase III, randomized, double-blind, evaluation in secondary stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate (110 mg or 150 mg, oral b.i.d.) versus aspirin (100 mg oral q.d.) in patients with embolic stroke of undetermined source (ESUS).

The goal of this study is to demonstrate that the efficacy of dabigatran etexilate (110 mg b.i.d. or 150 mg b.i.d., with dosing according to age and renal function), is superior to aspirin (100 mg once daily) for the prevention of stroke recurrence in patients with embolic stroke of undetermined source. In addition, the trial will also characterize the safety of dabigatran etexilate in this setting. Patients with ischemic ESUS within the last 3 months, or within 6 months if aged ≥ 60 years and also have an additional risk factor for stroke, will be eligible for inclusion.

It estimated that 6000 participants will be enrolled into this study over a three year period. Average individual patient participation will be approximately 21 months.

For more information, please see the ClinicalTrials.gov website:
https://clinicaltrials.gov/ct2/show/NCT02239120

Publication: Pending 

DEFUSE 3: Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 

Study Sponsor: National Institutes of Health (NIH) - National Institute for Neurologic Disorders and Stroke (NINDS). (StrokeNET and Stanford University)
Site Principal Investigator: Brett Meyer, MD (UCSD Hillcrest)
Study Period:   April 2016 – December 2017– CLOSED to Enrollment

The purpose of DEFUSE 3 is to assess the safety and efficacy of thrombectomy in carefully selected patients in an extended treatment time window. DEFUSE 3 is a prospective randomized Phase III multicenter controlled trial of patients with acute ischemic anterior circulation strokes due to large artery occlusion treated between 6-16 hours of stroke onset with endovascular thrombectomy therapy vs. control. Patients who meet the inclusion criteria will undergo either CT Perfusion/CTA or MR DWI/PWI/MRA studies prior to randomization. Patients who have evidence of an ICA or MCA M1 occlusion and a Target Mismatch Profile will be randomized in a 1:1 ratio to treatment with endovascular therapy (using one or more DEFUSE 3 approved thrombectomy devices) plus standard medical therapy versus standard medical therapy alone.

The primary endpoint, the modified Rankin Scale, will be assessed at 3 months. The patients' participation in the study concludes at that time (3 months from stroke onset). The study will randomize up to 476 patients over 4 years.

For more information, please see the ClinicalTrials.gov website:
https://clinicaltrials.gov/ct2/show/NCT02586415

Abstract Publication 

ACTION – 2: A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group, Dose-Ranging Study to Evaluate the Safety and Efficacy of Intravenous Natalizumab (BG00002) in Acute Ischemic Stroke

Study Sponsor: Biogen MA Inc
Site Principal Investigator: Thomas Hemmen, MD (UCSD Hillcrest)
Study Period:   August 2016 – December 2017 – CLOSED to Enrollment 

The ACTION 2 study (also known as 101SK202) will assess dose response and overall safety and efficacy of natalizumab in subjects with acute ischemic stroke. The primary objective of the study is to assess the effects of natalizumab versus placebo in acute ischemic stroke on clinical measures of independence and activities of daily life.

This study will be conducted in patients aged 18 to 80 years with acute ischemic stroke defined by last known normal at ≤ 9 hours prior to study treatment initiation. All subjects will receive 1 dose of study treatment at Screening according to their randomization into 1 of the following 3 treatment groups: 1) 600 mg natalizumab IV; 2) 300 mg of natalizamab IV; 3) placebo IV.

The study will randomize approximately 240 subjects from 60 sites in the United States and Europe. Subjects will participate in this study for approximately 90 days.

For more information, please see the ClinicalTrials.gov website:
https://clinicaltrials.gov/ct2/show/NCT02730455

Telerehabilitation in the Home Versus Therapy In-Clinic for Patients With Stroke

Study Sponsor: National Institutes of Health (NIH) - National Institute for Neurologic Disorders and Stroke (NINDS). (StrokeNET and University of California, Irvine)
Site Principal Investigator: Kunal Agrawal, MD
Study Period:   February 2015 – February 2018 – CLOSED to Enrollment

The current study will test the effectiveness of a novel home-based telehealth system designed to improve motor recovery and patient education after stroke. A total of 124 subjects (the number may be larger depending on the rate of subject dropout) with arm motor deficit 4-36 weeks after a stroke due to ischemia or to intracerebral hemorrhage will be randomized to receive 6 weeks of intensive arm motor therapy (a) in a traditional in-clinic setting or (b) via in-home telerehabilitation (rehabilitation services delivered to the subject's home via an internet-connected computer). The intensity, duration, and frequency of this therapy  will be identical across the two groups, with subjects in both treatment arms receiving 36 sessions (18 supervised and 18 unsupervised), 80 minutes each (including a 10 minute break), over 6 weeks. The primary endpoint is within-subject change in the arm motor Fugl-Meyer (FM) score from the Baseline Visit to 30 Day Follow-up Visit. Arm motor status is the focus here because it is commonly affected by stroke, is of central importance to many human functions, and is strongly linked to disability and well-being after stroke.

For more information, please see the ClinicalTrials.gov website:
https://clinicaltrials.gov/ct2/show/NCT02

Press Release

Questions?

To inquire about UCSD's Stroke Clinical Research program, please call the UCSD Stroke Center at 619-543-7760.

For general information about risk factors, signs and symptoms, and treatments visit the American Heart and Stroke Association website at:
http://www.strokeassociation.org/STROKEORG/