Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial
- Registration Number
- NCT00991029
- Lead Sponsor
- University of California, San Francisco
- Brief Summary
A transient ischemic attack (TIA) is a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. An ischemic stroke is a cerebral infarction. In POINT, eligibility is limited to brain TIAs and to minor ischemic strokes (with an NIH Stroke Scale \[NIHSS\] score less than or equal to 3).
TIAs are common \[25\], and are often harbingers of disabling strokes. Approximately 250,000-350,000 TIAs are diagnosed each year in the US. Given median survival of more than 8 years \[32\], there are approximately 2.4 million TIA survivors. In a national survey, one in fifteen of those over 65 years old reported a history of TIA \[33\], which is equivalent to a prevalence of 2.3 million in older Americans. Based on the prevalence of undiagnosed transient neurological events, the true incidence of TIA may be twice as high as the rates of diagnosis \[33\]. Based on our review of the National Inpatient Sample for 1997-2003, there were an average of 200,000 hospital admissions for TIA each year, with annual charges climbing quickly in the period to $2.6 billion in 2003.
Composite endpoint of new ischemic vascular events: ischemic stroke, myocardial infarction or ischemic vascular death at 90 days.
- Detailed Description
Platelet-Oriented Inhibition in New TIA and minor ischemic stroke (POINT) Trial, is a prospective, randomized, double-blind, multicenter trial with the primary null hypothesis that, in patients with TIA or minor ischemic stroke treated with aspirin 50-325 mg/day, there is no difference in the event-free survival at 90 days in those treated with clopidogrel (600 mg loading dose then 75 mg/day) compared to placebo when subjects are randomized within 12 hours of time last known free of new ischemic symptoms.
Its primary objective is to determine whether clopidogrel 75 mg/day by mouth after a loading dose of 600 mg of clopidogrel is effective in preventing major ischemic vascular events (ischemic stroke, myocardial infarction, and ischemic vascular death) at 90 days when initiated within 12 hours of TIA or minor ischemic stroke onset in patients receiving aspirin 50-325 mg/day (with a dose of 150-200 mg daily for 5 days followed by 75-100 mg daily strongly recommended).
Patients over 18 years of age with high-risk TIA (defined as an ABCD2 score greater than or equal to 4) or minor ischemic stroke (with NIHSS less than or equal to 3) who can be treated within 12 hours of time last known free of new ischemic symptoms will be enrolled.
Subjects will be randomized 1:1 (clopidogrel: placebo), controlling for clinical center. A study participant's eligibility will be determined by site personnel prior to accessing the Randomization Module in the WebDCU™, a web-enabled clinical trials management system that was developed by the NETT Statistics and Data Management Center (SDMC) at Medical University of South Carolina (MUSC).Qualified users will access the Randomization Interface and complete a protocol-specific eligibility checklist. If the Randomization Interface finds the patient to be eligible based on the information provided, a randomization number and a confirmatory e-mail are generated.
Each subject is followed for 90 days from randomization; the trial will be completed in 7 years.
A total of 5,840 patients will be recruited. Recruitment will occur over 90 months, with a goal rate of 0.40 subjects/site/month for US sites, and a goal rate of 0.47 subjects/site/month for OUS sites. Current participating sites can be found at: http://www.pointtrial.org/node/18.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4881
-
Neurological deficit (based on history or exam) attributed to focal brain ischemia and EITHER:
- High risk TIA: Complete resolution of the deficit at the time of randomization AND ABCD2 score of (greater than or equal to) 4 OR
- Minor ischemic stroke: residual deficit with NIHSS of (less than or equal to) 3 at the time of randomization
-
Ability to randomize within 12 hours of time last known free of new ischemic symptoms.
-
Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy.
-
Ability to tolerate aspirin at a does of 50-325 mg/day.
Exclusion Criteria
-
Age <18 years
-
TIA symptoms limited to isolated numbness, isolated visual changes, or isolated dizziness/vertigo.
-
In the judgment of the treating physician, a candidate for thrombolysis, endarterectomy or endovascular intervention, unless the subject declines both endarterectomy and endovascular intervention at the time of evaluation for eligibility.
-
Receipt of any intravenous or intra-arterial thrombolysis within 1 week prior to index event.
-
Gastrointestinal bleed or major surgery within 3 months prior to index event.
-
History of nontraumatic intracranial hemorrhage.
-
Clear indication for anticoagulation (e.g., warfarin, heparin) anticipated during the study period (atrial fibrillation, mechanical heart valve, deep venous thrombosis, pulmonary embolism, antiphospholipid antibody syndrome, hypercoagulable state).
-
Qualifying ischemic event induced by angiography or surgery.
-
Severe non-cardiovascular comorbidity with life expectancy <3 months.
-
Contraindication to clopidogrel or aspirin.
- Known allergy
- Severe renal (serum creatinine >2 mg/dL or 176.8umol/L) or hepatic insufficiency (prior or concurrent diagnosis, with International Normalized Ratio (INR)>1.5 or any resultant complication, such as variceal bleeding, encephalopathy, or icterus)
- Hemostatic disorder or systemic bleeding in the past 3 months
- Current thrombocytopenia (platelet count <100 x10^9/l) or neutropenia (<1 x10^9/l)
- History of drug-induced hematologic or hepatic abnormalities
-
Anticipated requirement for long-term (>7 day) non-study antiplatelet drugs (eg, dipyridamole, clopidogrel, ticlopidine), or Non-steroidal Anti-inflammatory Drugs (NSAIDs) affecting platelet function (such as prior vascular stent or arthritis).
-
Inability to swallow medications.
-
At risk for pregnancy: premenopausal or post menopausal woman within 12 months of last menses without a negative pregnancy test or not committing to adequate birth control (e.g., oral contraceptive, two methods of barrier birth control, or abstinence).
-
Unavailability for follow-up.
-
Signed and dated informed consent not obtained from patient.
-
Other neurological conditions that would complicate assessment of outcomes during follow-up.
-
Ongoing treatment in another study of an investigational therapy that may potentially interact with study drug, or treatment in such a study within the last 7 days.
-
Previously enrolled in the POINT study.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo placebo Patients assigned to placebo in addition to aspirin clopidogrel Clopidogrel Patients assigned to clopidogrel in addition to aspirin
- Primary Outcome Measures
Name Time Method Composite of Ischemic Stroke, Myocardial Infarction, or Death From Ischemic Vascular Causes Up to 90 days Primary efficacy outcome: Number of Participants with Ischemic Stroke, Myocardial Infarction, or Death From Ischemic Vascular Causes
Major Hemorrhage Up to 90 days Primary safety outcome: Number of Participants with major hemorrhage
- Secondary Outcome Measures
Name Time Method Ischemic Stroke Up to 90 days Secondary efficacy outcome:Number of participants with Ischemic stroke
Myocardial Infarction Up to 90 days Secondary efficacy outcome: Number of participants with Myocardial infarction
Death From Ischemic Vascular Causes Up to 90 days Secondary efficacy outcome: Number of participants with Death from ischemic vascular causes
Ischemic or Hemorrhagic Stroke Up to 90 days Secondary efficacy outcome: Number of participants with Ischemic or hemorrhagic stroke
Composite of Ischemic Stroke, Myocardial Infarction, Death From Ischemic Vascular Causes, or Major Hemorrhage Up to 90 days Secondary efficacy outcome: Number of participants with ischemic stroke, myocardial infarction, death from ischemic vascular causes, or major hemorrhage
Trial Locations
- Locations (209)
Chandler Regional Medical Center
🇺🇸Chandler, Arizona, United States
Banner University Medical Center - Tucson Campus
🇺🇸Tucson, Arizona, United States
George Washington University Hospital
🇺🇸Washington, District of Columbia, United States
Benefis Hospitals Inc
🇺🇸Great Falls, Montana, United States
Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Great Falls Clinic Hospital, Great Falls
🇺🇸Great Falls, Montana, United States
JFK Medical Center
🇺🇸Edison, New Jersey, United States
Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Cooper University Hospital
🇺🇸Camden, New Jersey, United States
Grey Nuns Hospital
🇨🇦Edmonton, Alberta, Canada
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Montreal General Hospital
🇨🇦Montreal, Quebec, Canada
Turku University Hospital
🇫🇮Turku, Finland
University Hospital of Ulm
🇩🇪Ulm, Baden-Württemberg, Germany
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Ben Taub General Hospital
🇺🇸Houston, Texas, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Mercy Health West Hospital
🇺🇸Cincinnati, Ohio, United States
Good Samaritan Hospital
🇺🇸Cincinnati, Ohio, United States
Jewish Hospital
🇺🇸Cincinnati, Ohio, United States
University of Texas Health Science Center San Antonio
🇺🇸San Antonio, Texas, United States
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
UCSD Health La Jolla
🇺🇸La Jolla, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Scripps Mercy Hospital San Diego
🇺🇸San Diego, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Los Robles Hospital and Medical Center
🇺🇸Thousand Oaks, California, United States
St. Anthony Hospital
🇺🇸Lakewood, Colorado, United States
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
University of Florida
🇺🇸Jacksonville, Florida, United States
Sarasota Memorial Hospital
🇺🇸Sarasota, Florida, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Alexian Brothers Medical Center
🇺🇸Elk Grove Village, Illinois, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
University of Illinois Hospital
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Presence Saint Joseph Medical Center
🇺🇸Joliet, Illinois, United States
St. Elizabeth Medical Center South
🇺🇸Edgewood, Kentucky, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Henry Ford West Bloomfield Hospital
🇺🇸West Bloomfield, Michigan, United States
Mercy Health Saint Mary's
🇺🇸Grand Rapids, Michigan, United States
William Beaumont Hospital - Troy
🇺🇸Troy, Michigan, United States
William Beaumont Hospital
🇺🇸Royal Oak, Michigan, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota Medical Center Hospital
🇺🇸Minneapolis, Minnesota, United States
Kings County Hospital Center
🇺🇸Brooklyn, New York, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Jersey Shore University Medical Center
🇺🇸Neptune, New Jersey, United States
SUNY Downstate Medical Center
🇺🇸Brooklyn, New York, United States
Guilford Neurologic Associates
🇺🇸Greensboro, North Carolina, United States
New York Presbyterian / Columbia University Medical Center
🇺🇸New York, New York, United States
Summa Akron City Hospital
🇺🇸Akron, Ohio, United States
Bethesda North Hospital
🇺🇸Cincinnati, Ohio, United States
Mount Carmel East Hospital
🇺🇸Columbus, Ohio, United States
University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
WellSpan York Hospital
🇺🇸York, Pennsylvania, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
John Hunter Hospital
🇦🇺New Lambton, New South Wales, Australia
The Northern Hospital
🇦🇺Epping, Victoria, Australia
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Vivantes Hospital Neukolln
🇩🇪Berlin, Germany
University Medical Center Hamburg
🇩🇪Hamburg, Germany
Neurosciences Clinical Trials
🇲🇽Culiacan, Sinaloa, Mexico
Royal United Hospital - Bath
🇬🇧Somerset, United Kingdom
Royal Stoke University Hospital
🇬🇧Stoke-on-Trent, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Strong Memorial Hospital
🇺🇸Rochester, New York, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
Detroit Receiving Hospital
🇺🇸Detroit, Michigan, United States
Harper University Hospital
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Sinai-Grace Hospital
🇺🇸Detroit, Michigan, United States
St. John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Providence St. Vincent Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University Hospital
🇺🇸Portland, Oregon, United States
Portland VA Medical Center
🇺🇸Portland, Oregon, United States
Vanderbilt University Hospital
🇺🇸Nashville, Tennessee, United States
Mayo Clinic Saint Mary's Campus
🇺🇸Rochester, Minnesota, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Columbia St. Mary's Hospital
🇺🇸Milwaukee, Wisconsin, United States
Froedtert Memorial Lutheran Hospital
🇺🇸Milwaukee, Wisconsin, United States
Aurora St. Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
UCSD Medical Center - Hillcrest Hospital
🇺🇸San Diego, California, United States
San Francisco General Hospital
🇺🇸San Francisco, California, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
Christiana Hospital
🇺🇸Newark, Delaware, United States
St. Elizabeth Hospital Fort Thomas
🇺🇸Fort Thomas, Kentucky, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
St. Elizabeth Hospital
🇺🇸Florence, Kentucky, United States
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
Frederick Memorial Hospital
🇺🇸Frederick, Maryland, United States
Lincoln Medical and Mental Health Center
🇺🇸Bronx, New York, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Southern Illinois University Memorial Medical Center
🇺🇸Springfield, Illinois, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Abbott Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital
🇺🇸Springfield, Missouri, United States
Buffalo General Medical Center
🇺🇸Buffalo, New York, United States
NYP Weill Cornell Medical Center
🇺🇸New York, New York, United States
Stony Brook University Hospital
🇺🇸Stony Brook, New York, United States
London Health Sciences Center
🇨🇦London, Ontario, Canada
Foch Hospital
🇫🇷Suresnes, France
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
OSU Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Palmetto Health Richland
🇺🇸Columbia, South Carolina, United States
Texas Health Presbyterian Hospital - Dallas
🇺🇸Dallas, Texas, United States
University of Calgary - Foothills Campus
🇨🇦Calgary, Alberta, Canada
Adolphe de Rothschild Ophthalmologic Foundation
🇫🇷Paris, France
Bichat-Claude Bernard Hospital
🇫🇷Paris, France
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
University Hospital Essen
🇩🇪Essen, Germany
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
Footscray Hospital
🇦🇺Footscray, Victoria, Australia
WVU Healthcare Ruby Memorial Hospital
🇺🇸Morgantown, West Virginia, United States
Charles LeMoyne Hospital
🇨🇦Greenfield Park, Quebec, Canada
Pierre Wetheimer Hospital
🇫🇷Bron, France
Neurological Clinic Bad Neustadt
🇩🇪Bad Neustadt an der Saale, Germany
Notre-Dame Hospital
🇨🇦Montreal, Quebec, Canada
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Pitie-Salpetriere Hospital
🇫🇷Paris, France
Fleyriat Hospital
🇫🇷Bourg-en-Bresse, France
The Royal London Hospital
🇬🇧London, United Kingdom
Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom
Hannover Medical School
🇩🇪Hannover, Germany
Enfant-Jesus Hospital
🇨🇦Quebec, Canada
University Hospital Frankfurt
🇩🇪Frankfurt, Germany
University Medical Center Leipzig
🇩🇪Leipzig, Germany
University Hospital Munster
🇩🇪Munster, Germany
University Hospital Schleswig-Holstein Kiel Campus
🇩🇪Kiel, Germany
University Hospital Heidelberg
🇩🇪Heidelberg, Germany
Mexican Association for Clinical Research
🇲🇽Pachuca, Hidalgo, Mexico
ABC Medical Center Santa Fe
🇲🇽Mexico City, Mexico
Central Hospital Dr. Ignacio Morones Prieto
🇲🇽San Luis PotosĂ, San Luis Potosi, Mexico
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Hospital del Mar
🇪🇸Barcelona, Spain
Vall d'Hebron Hospital
🇪🇸Barcelona, Spain
Hospital Donostia
🇪🇸Donostia, Spain
Culiacan General Hospital
🇲🇽Culiacan, Sinaloa, Mexico
Santa Creu and Sant Pau Hospital
🇪🇸Barcelona, Spain
Auckland City Hospital
🇳🇿Auckland, New Zealand
Basurto Hospital
🇪🇸Bilbao, Spain
La Fe University Hospital
🇪🇸Valencia, Spain
Northwick Park Hospital
🇬🇧Harrow, United Kingdom
Miguel Servet Hospital
🇪🇸Zaragoza, Spain
University College Hospital
🇬🇧London, United Kingdom
Luton and Dunstable University Hospital
🇬🇧Luton, United Kingdom
Desert Regional Medical Center
🇺🇸Palm Springs, California, United States
Huntington Memorial Hospital
🇺🇸Pasadena, California, United States
Evanston Hospital
🇺🇸Evanston, Illinois, United States
NorthShore Glenbrook Hospital
🇺🇸Glenview, Illinois, United States
University of Kentucky Hospital
🇺🇸Lexington, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University of Louisville Hospital
🇺🇸Louisville, Kentucky, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Christ Hospital
🇺🇸Cincinnati, Ohio, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Hahnemann University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Pennsylvania State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
UPMC Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Shadyside Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Valley Baptist Medical Center - Harlingen
🇺🇸Harlingen, Texas, United States
Memorial Hermann Texas Medical Center
🇺🇸Houston, Texas, United States
UVA Medical Center
🇺🇸Charlottesville, Virginia, United States
UMASS Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Central Bremen Hospital
🇩🇪Bremen, Germany
Girona University HOspital
🇪🇸Girona, Spain
Burgos University Hospital
🇪🇸Burgos, Spain
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Mercy General Hospital
🇺🇸Sacramento, California, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Rochester General Hospital
🇺🇸Rochester, New York, United States
Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Medical University of South Carolina University Hospital
🇺🇸Charleston, South Carolina, United States
University Medical Center Brackenridge
🇺🇸Austin, Texas, United States
Seton Medical Center
🇺🇸Austin, Texas, United States
Bon Secours St. Francis Medical Center
🇺🇸Richmond, Virginia, United States
Bon Secours St. Mary's Hospital
🇺🇸Richmond, Virginia, United States
Henrico Doctors' Hospital - Forest Campus
🇺🇸Richmond, Virginia, United States
Henrico Doctors' Hospital - Parham Campus
🇺🇸Richmond, Virginia, United States
UF Health Shands Hospital
🇺🇸Gainesville, Florida, United States
the Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States