Current Studies

• Acute Ischemic Stroke and Ischemic Stroke Trials at 18-36 Hours Post-Stroke

  Intrepid - Impact of Fever Prevention in Brain Injured Patients Multiple studies demonstrate that fever / elevated temperature is associated with poor outcomes in brain injured patients; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. This study will be conducted to assess the impact of advanced temperature control to prevent fever in brain injured patients. The fever prevention group will use the Arctic Sun Temperature Management System and will be compared to standard care patients in whom fever may spontaneously develop. If fever develops in a patient in the standard care group, they will be treated with standard fever care measures according to a step-wise algorithm, consisting primarily of intermittent antipyretics (e.g., acetaminophen) and cooling blankets and, when necessary, advanced targeted temperature management devices. PI: Huimahn A Choi Coordinator: Glenda L Torres

  Multi-arm Optimization of Stroke Thrombolysis (MOST) The primary efficacy objective of the MOST trial is to determine if argatroban (100µg/kg bolus followed by 3µg/kg per minute for 12 hours) or eptifibatide (135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours) results in improved 90-day modified Rankin scores (mRS) as compared with placebo in acute ischemic stroke (AIS) patients treated with 0.9mg/kg IV rt-PA within three hours of symptom onset. Patients may also receive endovascular thrombectomy (ET) per usual care. Time of onset is defined as the last time the patient was last known to be well. PI: Andrew Barreto, MD Coordinator: Jamey D. Franklin

  Sedation versus General Anesthesia for Endovascular Therapy in Acute Ischemic Stroke (SEGA) The majority of strokes are the result of blood clots in the main vessels that provide blood to the brain. When people suffer from a stroke, these blood clots produce a blockage to the normal flow of blood, which can cause brain tissue to be damaged. This often produces symptoms such as weakness or numbness to one side of the body, changes in vision, or changes in people’s abilities to speak or be understood. Although the body may break up the blood clots on its own, doctors also use a clot-busting drug called rt-PA for patients with certain types of stroke. Unfortunately, rt-PA is not always successful in breaking up clots. Larger clots can also be removed from the brain by performing an emergency surgery called endovascular therapy which can restore normal blood flow. Endovascular therapy with stent retrievers have been shown to improve outcomes in acute stroke patients. However, there is still some controversy about the best type of anesthesia – general anesthesia (GA) vs sedation (CS) to be used during endovascular therapy. The purpose of this study is to study whether GA during endovascular therapy results in better outcomes compared with CS during endovascular therapy among acute ischemic stroke patients. PI: Roc Chen, MD

  A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT 2) SELECT 2 evaluates the efficacy and safety of endovascular thrombectomy compared to medical management alone in acute ischemic stroke patients due to a large vessel occlusion in the distal ICA and MCA M1 who have large core on either CT (ASPECTS: 3-5) or advanced perfusion imaging ([rCBF<30%] on CTP or [ADC<620] on MRI: ≥50cc) or both and are treated within 0-24 hours from last known well. The second aim is to look at the correlation of imaging profiles with thrombectomy clinical outcomes and treatment effect. This will be evaluated by comparing the outcomes in patients with discordant imaging profile and assessing if thrombectomy outcome rates and treatment effect will differ in patients with discordant imaging profiles (favorable CT/unfavorable perfusion imaging and unfavorable CT/favorable perfusion imaging). PI: Amrou Sarraj, MD Coordinator: Faris Shaker

  Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke (TESLA) The primary objective of the trial is to establish the effectiveness of IAT (versus medical management) in patients with moderate-large infarcts (NCCT ASPECTS 2-5) at baseline, with adaptive enrichment to better define the upper limit of infarct volume for treatment eligibility. Furthermore, the investigators aim to determine whether certain subgroups of patients with large baseline infarcts will have a greater treatment benefit. Finally, the investigators will assess the agreement of ASPECTS scores between site investigators, the core imaging lab, and automated software. PI: Sunil Sheth, MD Coordinator: Victor S Lopez Rivera

  A Phase III, blinded, randomized trial of thrombolysis in imaging-eligible, late-window patients to assess the efficacy and safety of Tenecteplase (TIMELESS) This study will evaluate the efficacy and safety of a clot dissolving medication, tenecteplase, in patients with acute ischemic stroke (AIS) who arrive in the emergency department in the 4.5- to 24-hour time window. This may extend the treatment window from the current 4.5 hours restrictions to up to 24 hours after AIS. PI Andrew Barreto, MD

  
  
  

• Acute Brain Hemorrhage

  Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial (FASTEST) The objective of the rFVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial is to establish the first treatment for acute spontaneous intracerebral hemorrhage (ICH) within a time window and subgroup of patients that is most likely to benefit. The central hypothesis is that rFVIIa, administered within 120 minutes from stroke onset with an identified subgroup of patients most likely to benefit, will improve outcomes at 180 days as measured by the Modified Rankin Score (mRS) and decrease ongoing bleeding as compared to standard therapy. PI: James Grotta, MD Coordinator: Patti L Bratina

  Intrepid - Impact of Fever Prevention in Brain Injured Patients Multiple studies demonstrate that fever / elevated temperature is associated with poor outcomes in brain injured patients; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. This study will be conducted to assess the impact of advanced temperature control to prevent fever in brain injured patients. The fever prevention group will use the Arctic Sun Temperature Management System and will be compared to standard care patients in whom fever may spontaneously develop. If fever develops in a patient in the standard care group, they will be treated with standard fever care measures according to a step-wise algorithm, consisting primarily of intermittent antipyretics (e.g., acetaminophen) and cooling blankets and, when necessary, advanced targeted temperature management devices. PI: Huimahn A Choi, MD Coordinator: Glenda L Torres

• SAH Trials

  Prospective Trial of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage via Lumbar Catheter (PILLAR) The PILLAR-XT study is designed to further confirm safety and characterize efficacy of Neurapheresis therapy. The study works in tandem with the current SOC treatments for SAH and does not detract from the established care pathways, or deny enrolled subjects proven therapies. The PILLAR-XT study utilizes the established skill sets of chosen Investigators who are already trained in the treatment and care of SAH patients and insertion/management of lumbar drains.  The objective of this study is to further demonstrate safety and characterize effectiveness of the Neurapheresis™ System (extracorporeal system and catheter) to remove red blood cells (RBCs) and lysed blood by-products from hemorrhagic cerebrospinal fluid (CSF) following aneurysmal subarachnoid hemorrhage (aSAH). PI: Spiros Blackburn, MD

  Intrepid - Impact of Fever Prevention in Brain Injured Patients Multiple studies demonstrate that fever / elevated temperature is associated with poor outcomes in brain injured patients; however, there are no conclusive studies that demonstrate that fever prevention/controlled normothermia is associated with better outcomes. This study will be conducted to assess the impact of advanced temperature control to prevent fever in brain injured patients. The fever prevention group will use the Arctic Sun Temperature Management System and will be compared to standard care patients in whom fever may spontaneously develop. If fever develops in a patient in the standard care group, they will be treated with standard fever care measures according to a step-wise algorithm, consisting primarily of intermittent antipyretics (e.g., acetaminophen) and cooling blankets and, when necessary, advanced targeted temperature management devices. PI: Huimahn A Choi, MD Coordinator: Glenda L Torres

  Role of Haptoglobin Genotype on Neuroinflammation and Coagulation Following Aneurysmal Subarachnoid Hemorrhage (NIH K23NS106054) An estimated 2 percent of the population harbors an intracranial aneurysm, and every year more than 30,000 aneurysms will rupture in the U.S. Many who survive go on to have with crippling cognitive and motor deficits despite aggressive surgical and medical intervention. This project seeks to investigate the promising finding that Haptoglobin genotype predicts outcome after aneurysmal subarachnoid hemorrhage, and beyond this, novel mechanisms of inflammation and coagulation to determine future therapeutic targets. PI: Spiros Blackburn, MD

• In Hospital Studies

  Optimal Delay Time to Initiate Anticoagulation after Ischemic Stroke in Atrial Fibrillation (START) Primary Objective: To determine the optimal time to initiate anticoagulation with a Non-Vitamin K Oral Anticoagulant (NOAC) after ischemic stroke in patients with non-valvular atrial fibrillation. Secondary Objectives: To compare the rates of primary adverse outcomes in a per protocol analysis To compare 30 day clinical outcomes by the modified Rankin scale among the time-to-treatment groups To compare 30 day clinical outcomes by the PROMIS-10 scale among the time-to-treatment groups. To compare 90 day clinical outcomes by the modified Rankin scale among the time-to-treatment groups To explore the optimal timing in subgroups of age, sex, outcome category, and NOAC choice PI: Alicia Zha, MD

• Stroke Prevention Trials

  Optimal Delay Time to Initiate Anticoagulation after Ischemic Stroke in Atrial Fibrillation (START) Primary Objective: To determine the optimal time to initiate anticoagulation with a Non-Vitamin K Oral Anticoagulant (NOAC) after ischemic stroke in patients with non-valvular atrial fibrillation. Secondary Objectives: To compare the rates of primary adverse outcomes in a per protocol analysis To compare 30 day clinical outcomes by the modified Rankin scale among the time-to-treatment groups To compare 30 day clinical outcomes by the PROMIS-10 scale among the time-to-treatment groups. To compare 90 day clinical outcomes by the modified Rankin scale among the time-to-treatment groups To explore the optimal timing in subgroups of age, sex, outcome category, and NOAC choice PI: Alicia Zha, MD Coordinator: Gabretta Cooksey

  AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke (ARCADIA) 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 NINDS StrokeNet consortium. Subjects will be followed for a minimum of 1.5 years and a maximum of 7 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. PI: Anjail Sharrief, MPH, MD Coordinator: Gabretta Cooksey

  Sleep for Stroke Management and Recovery Trial (SLEEP-SMART) Sleep SMART has a prospective, randomized, open-label, blinded-endpoint (PROBE) design. It is a multi-site, parallel-group superiority trial that compares 6 months of OSA treatment to usual care. The study includes two trials: a prevention study with an embedded recovery trial. 3062 subjects will be randomized over 5 years at 110 sites within the NINDS-funded StrokeNet clinical trials network. The purpose of this study is to determine whether treatment of obstructive sleep apnea (OSA) with positive airway pressure starting shortly after acute ischemic stroke or high risk TIA (1) reduces recurrent stroke, acute coronary syndrome, and all-cause mortality 6 months after the event, and (2) improves stroke outcomes at 3 months in patients who experienced an ischemic stroke. PI: Anjail Sharrief, MPH, MD Coordinator: Audrey Cohen

  Stroke Telemedicine Outpatient Prevention Program for Blood Pressure Reduction (STOP STROKE) The purpose of this pilot trial is to compare post-stroke care blood pressure (BP) treatment using an interdisciplinary telehealth model [called the Stroke Telemedicine Outpatient Program (STOP) for Blood Pressure Reduction] to usual care in stroke patients at risk for uncontrolled BP. The intervention will address general and stroke-related factors associated with racial disparities in BP control. We will assess feasibility of implementation of the trial and will use the measures and outcomes assessed in the pilot to examine knowledge gaps. PI: Anjail Sharrief, MPH, MD Coordinator: Gabretta Cooksey

  A Study on BMS-986177 for the Prevention of a Stroke in Patients Receiving Aspirin and Clopidogrel (AXIOMATIC) The purpose of this clinical study is to determine whether the addition of an oral Factor XIa Inhibitor to Aspirin and Clopidogrel is more effective than standard therapy in secondary stroke prevention. PI: Anjail Sharrief, MPH, MD Coordinator: Audrey Cohen

  Anticoagulation for Stroke Prevention and Recovery after ICH (ASPIRE) ASPIRE is a randomized, double-blinded, phase III clinical trial designed to test the efficacy and safety of anticoagulation, compared with aspirin, in patients with a recent ICH and high-risk non-valvular AF (CHA2DS2-VASc score ≥ 2). Seven hundred patients will be enrolled over 3.5 years and followed for study outcomes for a minimum of 12 months and maximum of 36 months. The primary efficacy outcome is any stroke (hemorrhagic or ischemic) or death from any cause. The secondary efficacy outcome is the change in the modified Rankin Scale score. Recruitment will take place at sites coordinated through the NIH/NINDS StrokeNet. Primary Aim: To determine if apixaban is superior to aspirin for prevention of the composite outcome of any stroke (hemorrhagic or ischemic) or death from any cause in patients with recent ICH and atrial fibrillation (AF). Secondary Aim: To determine if apixaban, compared with aspirin, results in better functional outcomes as measured by the modified Rankin Scale. PI: Andrew Baretto, MD Coordinator: Prasen Marella

   

• Recovery Trials

  TRANScranial direct current stimulation for Post-stroke motor Recovery – a phase II sTudy (TRANSPORT-2) This research study is to find out if brain stimulation at different dosage level combined with an efficacy-proven rehabilitation therapy can improve arm function. The stimulation technique is called transcranial direct current stimulation (tDCS). The treatment uses direct currents to stimulate specific parts of the brain affected by stroke. The adjunctive rehabilitation therapy is called "modified Constraint-Induced Movement Therapy" (mCIMT). During this therapy the subject will wear a mitt on the hand of the arm that was not affected by a stroke and force to use the weak arm. The study will test 3 different doses of brain stimulation in combination with mCIMT to find out the most promising one. PI: Gerard Francisco, MD Coordinator: Dorothea M Parker

  Perinatal Arterial Stroke: A Multi-site RCT of Intensive Infant Rehabilitation (I-AQUIRE) This is a Phase III clinical trial to compare the efficacy of two dosages of a new infant rehabilitation protocol - I-ACQUIRE - to usual and customary forms of infant rehabilitation in infants who experienced Perinatal Arterial Stroke (PAS). The proposed study is a Phase III trial powered to determine efficacy of two different doses of I-ACQUIRE for children 8 to 36 months old with PAS and hemiparesis. The design is a prospective Randomized Controlled Trial (RCT) in which 240 children will be randomly assigned to one of 3 treatment groups (N=80 per group): 1) Moderate Dose I-ACQUIRE (3 hours/day, 5 day/week X 4 weeks), 2) High Dose I-ACQUIRE (6hrs/day, 5 days/week X 4 weeks), or 3) Usual and Customary Treatment (U&CT). I-ACQUIRE will be delivered by protocol-trained therapists and monitored weekly for dosage and treatment fidelity; U&CT will be provided by community therapists with dosage and approaches documented weekly. All primary and secondary efficacy outcomes rely on blinded assessments at baseline, end of treatment, and 6 months post-treatment. Exploratory outcomes and supplemental clinical measures may provide valuable additional data about development and health in this sample of children with PAS. PI: Stuart Fraser, MD Coordinator: Samantha Acosta, MA Contact: Samantha.D.Acosta@uth.tmc.edu

  Ischemic Stroke Trials at 18-36 hours Post-stroke

  MultiStem® Administration for Stroke Treatment and Enhanced Recovery Study (MASTERS-2) MultiStem is an allogeneic, regenerative medicine advanced therapy (stem cells) indicated for treatment of acute ischemic stroke within 36 hours after symptom onset. The objectives of this study are to evaluate the efficacy and safety of MultiStem on functional outcome in participants with ischemic stroke. Further, we want to evaluate the impact of MultiStem on a patient’s quality of life and healthcare and rehabilitation services utilization; and to evaluate the mechanism of action of MultiStem through blood biomarkers, and spleen and brain imaging outcomes in subjects. This is a randomized blinded study. PI Sean Savitz, MD Coordinator: Parker, Dorothea M <Dorothea.M.Parker@uth.tmc.edu>

  NCS-01 (KPharma / IA stem cell) This is an initial Phase1/2 dose-finding, double-blind, placebo-controlled, multi-center study to evaluate the safety and tolerability of NCS-01 in patients with acute ischemic stroke. All patients will be randomized within 24 hours of stroke onset. This study will be conducted in 2 stages. PI: Sean Savitz, MD Coordinator: Dorothea M Parker