Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial "POINT"

Recruiting

Phase 3 Results N/A

Trial Description

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.

Conditions

Interventions

  • Clopidogrel (Plavix®)Drug
    Other Names: Plavix
    Intervention Desc: Loading dose of 600mg followed by 75 milligrams, oral, one tablet daily for 89 days
    ARM 1: Kind: Experimental
    Label: clopidogrel
    Description: Patients assigned to clopidogrel in addition to aspirin
  • Placebo Drug
    Intervention Desc: Loading dose of 8 tablets followed by one tablet daily for 89 days
    ARM 1: Kind: Experimental
    Label: placebo
    Description: Patients assigned to placebo in addition to aspirin

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Investigator)
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patient will be randomized to one of two arms: a) Patients assigned to clopidogrel (Loading dose of 600mg followed by 75 milligrams,oral, one tablet daily for 90 days) in addition to aspirin or b) Patients assigned to placebo (loading dose of 8 tablets followed by one tablet daily for 90 days)in addition to aspirin. Patients will have baseline Head CT or MRI ruling out hemorrhage or other pathology, such as vascular malformation, tumor, or abscess, that could explain symptoms or contraindicate therapy. Patients are then followed for 90 days to observe for major ischemic vascular events.

Outcomes

Type Measure Time Frame Safety Issue
Primary New ischemic vascular events (ischemic stroke, myocardial infarction, and ischemic vascular death.
Secondary 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.
Primary New ischemic vascular events (ischemic stroke, myocardial infarction, and ischemic vascular death 90 days Yes

Sponsors