Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial
Condition: Ischemic Attack, Transient
MeSH terms: Ischemic Stroke; Ischemic Attack, Transient; Ischemia
Intervention: Clopidogrel; placebo
Intervention description: Loading dose of 600mg followed by 75 milligrams, oral, one tablet daily for 89 days; Loading dose of 8 tablets followed by one tablet daily for 89 days
Intervention MeSH terms: Clopidogrel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 4881.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Transient Ischemic Attack; TIA; minor stroke

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.
    

Eligibility 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, 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.