Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial - Full Text View

Sponsor:	University of California, San Francisco
Collaborators:	Neurological Emergencies Treatment Trials Network (NETT) Medical University of South Carolina The EMMES Corporation
Information provided by (Responsible Party):	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00991029

Sponsor:

University of California, San Francisco

Collaborators:

Neurological Emergencies Treatment Trials Network (NETT)
Medical University of South Carolina
The EMMES Corporation

Information provided by (Responsible Party):

University of California, San Francisco

ClinicalTrials.gov Identifier:

NCT00991029

Purpose

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 <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.

Condition	Intervention	Phase
Ischemic Attack, Transient	Drug: Clopidogrel Drug: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack Transient Ischemic Attack

Drug Information available for: Clopidogrel Clopidogrel Bisulfate

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

New ischemic vascular events (ischemic stroke, myocardial infarction, and ischemic vascular death [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

secondary outcomes will be evaluated, separately including risk of ischemic stroke, intracranial hemorrhage, and major hemorrhage, and the composite of the primary outcome and major hemorrhage. [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	4150
Study Start Date:	October 2009
Estimated Study Completion Date:	September 2016
Estimated Primary Completion Date:	June 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: clopidogrel Patients assigned to clopidogrel in addition to aspirin	Drug: Clopidogrel Loading dose of 600mg followed by 75 milligrams,oral, one tablet daily for 90 days Other Name: Plavix
Placebo Comparator: placebo Patients assigned to placebo in addition to aspirin	Drug: placebo Loading dose of 8 tablets followed by one tablet daily for 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 162 mg daily for 5 days followed by 81 mg daily strongly recommended).

Patients over 18 years of age with high-risk TIA (defined as an ABCD2 score > 4) or minor ischemic stroke (with NIHSS < 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 4,150 patients will be recruited. Recruitment will occur over 66 months, with a goal rate of 0.42 subjects/site/month.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
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 hepatic insufficiency (prior or concurrent diagnosis, with 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 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.
Inability to provide informed consent.
Other neurological conditions that would complicate assessment of outcomes during follow-up.
Ongoing treatment in another study of an investigational therapy or treatment in such a study within the last 7 days.

United States, California
University of California San Francisco Stroke Sciences Group	Recruiting
San Francisco, California, United States, 94143
Contact: Mary Farrant, MBA BSN RN 415-502-2096 mary.farrant@ucsfmedctr.org

Principal Investigator:	S. Claiborne Johnston, MD, PhD	University of California, San Francisco
Principal Investigator:	J. Donald Easton, MD	University of California, San Francisco

Responsible Party:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00991029 History of Changes
Other Study ID Numbers:	1U01S062835-01A1
Study First Received:	October 6, 2009
Last Updated:	January 23, 2012
Health Authority:	United States: Institutional Review Board