Clinical trial NCT03936361: Statins In Intracerbral Hemorrhage
Official title: STATINS USE IN INTRACEREBRAL HEMORRHAGE PATIENTS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Intracerebral Hemorrhage
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: NINDS Stroke Trials Network (StrokeNet)
name: Canadian Stroke Consortium (CSC)
name: University of Cincinnati
name: Medical University of South Carolina
name: Yale University
name: MetroHealth Medical Center
name: UH, Cleveland Medical Center
name: Spectrum Health Hospitals
name: West Virginia University
name: Columbia University
name: Weill Medical College of Cornell University
name: New York Presbyterian Brooklyn Methodist Hospital
name: Buffalo General Medical Center
name: State University of New York - Upstate Medical University
name: St. Joseph's Regional Medical Center, New Jersey
name: Tufts Medical Center
name: Massachusetts General Hospital
name: UMass Memorial Health
name: Brigham and Women's Hospital
name: Baystate Medical Center
name: University of Vermont Medical Center
name: Lahey Hospital & Medical Center
name: Augusta University Medical Center
name: Prisma Health-Upstate
name: The Moses H. Cone Memorial Hospital
name: University of Virginia
name: George Washington University
name: University of Maryland, Baltimore
name: Mount Sinai Hospital, New York
name: NYU Langone Medical Center - Tisch Hospital
name: Montefiore Medical Center
name: NYU Langone Hospital - Brooklyn
name: Froedtert Hospital
name: Central DuPage Hospital
name: Rush University Medical Center
name: Loyola University
name: Stanford University
name: Mercy San Juan Medical Center
name: Oregon Health and Science University
name: Kaiser Permanente
name: University of Southern California
name: Cedars-Sinai Medical Center
name: University of New Mexico
name: Long Beach Memorial Medical Center
name: University of California, Irvine
name: Arrowhead Regional Medical Center
name: Huntington Memorial Hospital
name: Scripps Health
name: University of California, San Diego
name: Ochsner Health System
name: St. Joseph's Hospital and Medical Center, Phoenix
name: Desert Care Network
name: Eden Medical Center
name: San Francisco General Hospital
name: University of California, San Francisco
name: University of Louisville
name: Ohio State University
name: University of Iowa
name: Sanford Medical Center Fargo
name: University of Nebraska
name: Tampa General Hospital
name: University of Florida
name: Jackson Health System
name: Mayo Clinic
name: Baptist Medical Center Jacksonville
name: Wayne State University
name: University of Michigan
name: Mercy Health Saint Mary Grand Rapids
name: Metro Health, Michigan
name: University of Kentucky
name: McLaren Health Care
name: Regions Hospital
name: Allina Health System
name: University of Kansas
name: University of Minnesota
name: St. Cloud Hospital
name: Milton S. Hershey Medical Center
name: Abington Memorial Hospital
name: Temple University
name: University of Pennsylvania
name: Lehigh Valley Hospital
name: York Hospital, York, PA
name: Thomas Jefferson University
name: University of Pittsburgh
name: St. David's HealthCare
name: Baylor College of Medicine
name: Tulane Medical Center
name: The University of Texas Health Science Center at San Antonio
name: OU Medical Center
name: University of Utah
name: Swedish Medical Center
name: St. Mary's Medical Center
name: Banner University Medical Center
name: Intermountain Medical Center
name: Legacy Emanuel Medical Center
name: Sacred Heart Medical Center Springfield
name: Harborview Injury Prevention and Research Center
name: University of Wisconsin, Madison
name: Aurora BayCare Medical Center
name: Wake Forest University Health Sciences
name: University of Alabama at Birmingham
name: University of South Alabama
name: Carolinas Medical Center
name: Barnes-Jewish Hospital
name: St. Luke's Hospital, Kansas City, Missouri
name: University of Arkansas
name: OSF Healthcare System
name: Cox Medical Center South
name: North Shore University Hospital
name: Rhode Island Hospital
name: Hartford Hospital
name: Staten Island University Hospital
name: Johns Hopkins University
name: University of North Carolina, Chapel Hill
name: University of Alberta
name: The Ottawa Hospital
name: London Health Sciences Centre
name: Hamilton General Hospital
name: Hopital de l'Enfant-Jesus
name: Montreal Neurological Institute and Hospital
name: Foothills Medical Centre
name: University Health Network, Toronto
name: Health Sciences Centre, Winnipeg, Manitoba
name: Thunder Bay Regional Health Sciences Centre
name: Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre
name: Fraser Health
name: Hopital de Chicoutimi
name: Université de Sherbrooke
First posted: 2019-05-03
Enrollment: 1456
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recurrent symptomatic ICH
timeFrame: within 24 months
Secondary outcomes:
measure: Major Adverse Cerebro- and Cardio-Vascular Events
timeFrame: Within 24 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
References:
citation: Szejko N, Kirsch E, Falcone GJ. Genetic determinants of LDL cholesterol and risk of intracerebral haemorrhage. Curr Opin Lipidol. 2021 Aug 1;32(4):244-248. doi: 10.1097/MOL.0000000000000761.