NIH StrokeNet Prevention Trials

Statins Use in Intracerebral Hemorrhage Patient (SATURN)
Location: University of Virginia, George Washington University, University of Maryland
Summary: SATURN is a multi-center, prospective, randomized, phase 3, pragmatic, open-label, and blinded end-point assessment (PROBE) clinical trial to determine the effects of continuation vs. discontinuation of statins on the risk of intracerebral hemorrhage (ICH) recurrence in patients with lobar hemorrhage. A total of 1,456 patients will be recruited at ~ 140 sites in the United States and Canada coordinated through the NIH/NINDS StrokeNet. Participants presenting within 7 days of a spontaneous lobar ICH while taking statins will be randomized to one of two treatment strategies: discontinuation vs. continuation (restarting) of statin therapy (using the same agent and dose that they were using at ICH onset). Subjects will undergo baseline testing for APOE genotype and will be followed for 24 months to assess for the occurrence of recurrent symptomatic ICH and/or MACCE. Participants will also undergo repeated assessments of quality of life, modified Rankin Scale, and Montreal Cognitive Assessment during the 2-year follow-up period.

Anticoagulation for Stroke Prevention and Recovery after ICH (ASPIRE)
Location: MedStar Washington Hospital Center, University of Virginia, MedStar Georgetown University Hospital
Summary: ASPIRE is a randomized, double-blinded, phase 3 clinical trial designed to test the efficacy and safety of apixaban, compared with aspirin, in patients with a recent intracerebral hemorrhage (ICH) and high-risk non-valvular atrial fibrillation (AF). Seven hundred patients will be recruited at sites coordinated through the NIH/NINDS StrokeNet. Participants will be followed for outcomes over a median of 24 months (12 months minimum, 36 months maximum). Efficacy outcomes are stroke or death (primary) and change in modified Rankin Scale score (secondary). Tertiary outcomes include change in cognition and quality of life, major hemorrhage, myocardial infarction, venous thromboembolism, systemic embolism, and individual components of the primary outcome.
Contact: For more information, email ASPIRE@yale.edu

Sleep for Stroke Management and Recovery Trial (Sleep SMART)
Location: University of Virginia, George Washington University, University of Maryland
Summary: The primary goals of this study are 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 during 6 months after the event, and (2) improves stroke outcomes at 3 months in patients who experienced an ischemic stroke. Prior studies have shown a clear independent association between OSA, which has a prevalence similar to hypertension among stroke patients, and development of stroke and poor outcomes after ischemic stroke. If the Sleep SMART hypotheses are confirmed, a new strategy to prevent stroke recurrence and improve stroke recovery will be available.

Cognition and Silent Infarcts (ARCADIA CSI)
Location: MedStar Washington Hospital Center, University of Virginia, University of Maryland, MedStar Georgetown Univeristy Hospital
Summary: Cognitive decline and dementia after stroke is a major public health problem, with risk of dementia more than doubling after stroke and affecting more the 2 million people in the United States alone.  Yet, there are no effective treatments to prevent cognitive decline and dementia after stroke.  Silent brain infarction has been associated with cognitive decline, especially among those at high risk for cardio-embolism.  It is therefore likely that treatments that reduce the incidence of silent infarcts in stroke patients at high risk for cardio-embolism, will also reduce the rate of cognitive decline and dementia.  To test this, we will conduct an ancillary study to the NINDS-sponsored ARCADIA trial.  ARCADIA compares treatment with apixaban versus aspirin to prevent a recurrent clinical stroke in subjects with cryptogenic stroke and left atrial cardiopathy. We are taking advantage of the parent trial to address the possibility that apixaban might also reduce the incidence of silent infarction and be associated with better cognitive function over time compared to aspirin.

Atrial Cardiopathy and Antithrombotic Drugs in Prevention after Cryptogenic Stroke (ARCADIA) 
Location: MedStar Washington Hospital Center, University of Virginia, University of Maryland, MedStar Georgetown University Hospital 
Summary: 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 arise from left atrial thromboembolism that goes unrecognized because it is not associated with atrial fibrillation/flutter (AF). Under the prevailing clinical paradigm, it is thought that AF is required for blood clots to form in the left atrium. Therefore, unless AF is apparent, patients do not receive anticoagulant therapy to prevent atrial thromboembolism. However, recent research indicates that embolization from the left atrium can occur when there are abnormal changes to atrial tissue and function even before there is AF. Such an “atrial cardiopathy” may explain many of the strokes that are currently of unknown cause. Since anticoagulant drugs such as apixaban have already proven more effective than standard aspirin therapy for preventing stroke from AF, the parallels between AF and atrial cardiopathy suggest that apixaban may also be more effective than aspirin for stroke prevention in patients with atrial cardiopathy and no AF. ARCADIA is a randomized trial of apixaban versus aspirin specifically in patients with cryptogenic stroke who have evidence of atrial cardiopathy. This trial will address several important knowledge gaps. First, it will advance our understanding of stroke pathophysiology by assessing whether atrial cardiopathy is a valid therapeutic target, which may set the stage for a primary prevention trial. Second, this trial will advance our understanding of optimal secondary stroke prevention therapy. 
Contact: For more information, contact Preethy Feit at (202) 877-1932