Intracerebral Hemorrhage
Conditions
Brief summary
The SATURN trial aims to determine whether continuation vs. discontinuation of statin drugs after spontaneous lobar intracerebral hemorrhage (ICH) is the best strategy; and whether the decision to continue/discontinue statins should be influenced by an individual's Apolipoprotein-E (APOE) genotype. An MRI ancillary study (SATURN MRI), in a subset of SATURN participants , will evaluate the effects of continuation vs. discontinuation of statin drugs on hemorrhagic and ischemic MRI markers of cerebral small vessel disease, and whether the presence/burden of hemorrhagic markers (i.e. cerebral microbleeds and/or cortical superficial siderosis) on baseline MRI influences the risk of ICH recurrence on/off statin therapy.
Detailed description
SATURN is a multi-center, pragmatic, prospective, randomized, open-label, and blinded end-point assessment (PROBE) clinical trial. A total of 1,456 patients presenting within 7 days of a spontaneous lobar ICH while taking statins will be randomized to one of two treatment strategies: discontinuation vs. continuation of statin therapy (using the same agent and dose that they were using at ICH onset). Participating subjects will undergo baseline testing for APOE genotype and will be followed for 24 months to assess for the occurrence of recurrent symptomatic ICH or major adverse cerebro-/cardio-vascular events (MACCE) during the follow-up period. A subset of SATURN participants will participate in the optional MRI study, where they will undergo a baseline MRI within 7 days of randomization into SATURN and a repeat MRI at the end of the follow-up period. Recruitment will take place at \ 140 sites coordinated through the NIH/NINDS StrokeNet and the Canadian Stroke Consortium.
Interventions
DRUGStatins
Statin drugs (already prescribed) at ICH onset will be either continued or discontinued by the participants following qualifying ICH
Sponsors
NINDS Stroke Trials Network (StrokeNet)
Canadian Stroke Consortium (CSC)
University of Cincinnati
Medical University of South Carolina
Yale University
MetroHealth Medical Center
UH, Cleveland Medical Center
Corewell Health West
West Virginia University
Columbia University
Weill Medical College of Cornell University
New York Presbyterian Brooklyn Methodist Hospital
Buffalo General Medical Center
State University of New York - Upstate Medical University
St. Joseph's Regional Medical Center, New Jersey
Tufts Medical Center
Massachusetts General Hospital
UMass Memorial Health
Brigham and Women's Hospital
Baystate Medical Center
University of Vermont Medical Center
Lahey Hospital & Medical Center
Augusta University Medical Center
Prisma Health-Upstate
The Moses H. Cone Memorial Hospital
University of Virginia
George Washington University
University of Maryland, Baltimore
Mount Sinai Hospital, New York
NYU Langone Medical Center - Tisch Hospital
Montefiore Medical Center
NYU Langone Hospital - Brooklyn
Froedtert Hospital
Central DuPage Hospital
Rush University Medical Center
Loyola University
Stanford University
Mercy San Juan Medical Center
Oregon Health and Science University
Kaiser Permanente
University of Southern California
Cedars-Sinai Medical Center
University of New Mexico
Long Beach Memorial Medical Center
University of California, Irvine
Arrowhead Regional Medical Center
Huntington Memorial Hospital
Scripps Health
University of California, San Diego
Ochsner Health System
St. Joseph's Hospital and Medical Center, Phoenix
Desert Care Network
Eden Medical Center
San Francisco General Hospital
University of California, San Francisco
University of Louisville
Ohio State University
University of Iowa
Sanford Medical Center Fargo
University of Nebraska
Tampa General Hospital
University of Florida
Jackson Health System
Mayo Clinic
Baptist Medical Center Jacksonville
Wayne State University
University of Michigan
Mercy Health Saint Mary Grand Rapids
Metro Health, Michigan
University of Kentucky
McLaren Health Care
Regions Hospital
Allina Health System
University of Kansas
University of Minnesota
St. Cloud Hospital
Milton S. Hershey Medical Center
Abington Memorial Hospital
Temple University
University of Pennsylvania
Lehigh Valley Hospital
York Hospital, York, PA
Thomas Jefferson University
University of Pittsburgh
St. David's HealthCare
Baylor College of Medicine
Tulane Medical Center
The University of Texas Health Science Center at San Antonio
OU Medical Center
University of Utah
Swedish Medical Center
St. Mary's Medical Center
Banner University Medical Center
Intermountain Medical Center
Legacy Emanuel Medical Center
Sacred Heart Medical Center Springfield
Harborview Injury Prevention and Research Center
University of Wisconsin, Madison
Aurora BayCare Medical Center
Wake Forest University Health Sciences
University of Alabama at Birmingham
University of South Alabama
Carolinas Medical Center
Barnes-Jewish Hospital
St. Luke's Hospital, Kansas City, Missouri
University of Arkansas
OSF Healthcare System
Cox Medical Center South
North Shore University Hospital
Rhode Island Hospital
Hartford Hospital
Staten Island University Hospital
Johns Hopkins University
University of North Carolina, Chapel Hill
University of Alberta
The Ottawa Hospital
London Health Sciences Centre
Hamilton General Hospital
Hopital de l'Enfant-Jesus
Montreal Neurological Institute and Hospital
Foothills Medical Centre
University Health Network, Toronto
Health Sciences Centre, Winnipeg, Manitoba
Thunder Bay Regional Health Sciences Centre
Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre
Fraser Health
Hopital de Chicoutimi
Université de Sherbrooke
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Participants will be randomized at 1:1 ratio to either continue the same statin drug and dosage that they are taking at the time of ICH onset or to discontinue it for up to 24 months after ICH. No placebo will be prescribed for those randomized to discontinue statins.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 50 years. 2. Spontaneous lobar ICH confirmed by CT or MRI scan 3. Patient was taking a statin drug at the onset of the qualifying/index ICH 4. Randomization can be carried out within 7 days of the onset of the qualifying ICH 5. Patient or legally authorized representative, after consultation with the statin prescriber, agrees to be randomized to statin continuation (restart) vs. discontinuation
Exclusion criteria
1. Suspected secondary cause for the qualifying ICH, such as an underlying vascular abnormality or tumor, trauma, venous infarction, or hemorrhagic transformation of an ischemic infarct. 2. History of recent myocardial infarction (attributed to coronary artery disease) or unstable angina within the previous 3 months 3. Diabetic patients with history of myocardial infarction or coronary revascularization 4. History of familial hypercholesterolemia 5. Patients receiving proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors 6. Known diagnosis of severe dementia 7. Inability to obtain informed consent 8. Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, or other obvious reasons for noncompliance, such as unable to adhere to the protocol specified visits/assessments. 9. Life expectancy of less than 24 months due to co-morbid terminal conditions. 10. Pre-morbid mRS \>3 11. ICH score \>3 upon presentation. 12. Contraindications to continuation/resumption of statin therapy, such as significant elevations of serum creatinine kinase and/or liver transaminases, and rhabdomyolysis 13. Woman of childbearing potential 14. Concurrent participation in another research protocol for investigation of experimental therapy. 15. Indication that withdrawal of care will be implemented for the qualifying ICH.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recurrent symptomatic ICH | within 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Major Adverse Cerebro- and Cardio-Vascular Events | Within 24 months |
Countries
United States
Contacts
Primary ContactMagdy Selim, MD, PhD
Outcome results
None listed