Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial: Rationale and design
- Disclosure: S. C. Johnston is funded by NIH grants 1U01 NS062835 and UL1 RR024131, has received research support from the American Heart Association, is coeditor of Journal Watch Neurology and vice editor of the Annals of Neurology, is a coholder of a patent on an RNA panel to identify and risk-stratify transient ischemic attacks, indirectly receives research support from Sanofi (drug and placebo for this NIH-sponsored trial), and receives research support from AstraZeneca. J. D. Easton is funded by NIH grant 1U01 NS062835, is a consultant for Bristol-Myers Squibb; receives research support from AstraZeneca, and is on data monitoring noards for Daiichi-Sankyo, Schering-Plough Research Institute, Novartis, Cerevast Therapeutics, Acorda Therapeutics, and Johnson and Johnson, Inc. William Barsan is funded by NIH grants 2U01NS056975-06, 2U01NS056975-06, U01NS073476-01, U01 NS 062835, 1U01NS062778, and 1-U01-NS-069498-01. Anne Lindblad is an owner of The EMMES Corporation and through her employment at EMMES is supported by grants and contracts from the DoD, NEI, NINDS, and Acucela. Lewis Morgenstern is funded by NIH grants U01 NS062835, R01 HL098065, R01 NS070941, R18 HS017690, R01 NS38916, R01 NS062675, and U01 NS056975. Mary Farrant, Holly Battenhouse, Robin Conwit, Catherine Dillon, Jordan Elm, Sharon N. Poisson, and Yuko Palesch declare no funding or potential conflict of interest.
- Clinical Trial Registration – URL: http://www.clinicaltrials.gov Unique identifier: NCT00991029.
Correspondence: S. Claiborne Johnston, UCSF Department of Neurology, UCSF Clinical and Translational Science Institute, Sandler Neurosciences Bldg., 675 Nelson Rising Lane, San Francisco, CA 94158-0663, USA.
Ischemic stroke and other vascular outcomes occur in 10–20% of patients in the three-months following a transient ischemic attack or minor ischemic stroke, and many are disabling. The highest risk period for these outcomes is the early hours and days immediately following the ischemic event. Aspirin is the most common antithrombotic treatment used for these patients.
The aim of POINT is to determine whether clopidogrel plus aspirin taken <12 h after transient ischemic attack or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk, and acceptably safe, compared with aspirin alone.
POINT is a prospective, randomized, double-blind, multicenter trial in patients with transient ischemic attack or minor ischemic stroke. Subjects are randomized to clopidogrel (600 mg loading dose followed by 75 mg/day) or matching placebo, and all will receive open-label aspirin 50–325 mg/day, with a dose of 162 mg daily for five-days followed by 81 mg daily strongly recommended.
The primary efficacy outcome is the composite of new ischemic vascular events – ischemic stroke, myocardial infarction, or ischemic vascular death – by 90 days. The primary safety outcome is major hemorrhage, which includes symptomatic intracranial hemorrhage.
Aspirin is the most common antithrombotic given to patients with a stroke or transient ischemic attack, as it reduces the risk of subsequent stroke. This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin, initiated acutely, is more effective than aspirin alone.