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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00991029
Recruitment Status : Terminated (The trial was halted by the DSMB.)
First Posted : October 7, 2009
Results First Posted : December 4, 2018
Last Update Posted : December 4, 2018
Sponsor:
Collaborators:
Neurological Emergencies Treatment Trials Network (NETT)
Medical University of South Carolina
The Emmes Company, LLC
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE October 6, 2009
First Posted Date  ICMJE October 7, 2009
Results First Submitted Date  ICMJE October 4, 2018
Results First Posted Date  ICMJE December 4, 2018
Last Update Posted Date December 4, 2018
Actual Study Start Date  ICMJE May 28, 2010
Actual Primary Completion Date April 9, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
  • Composite of Ischemic Stroke, Myocardial Infarction, or Death From Ischemic Vascular Causes [ Time Frame: Up to 90 days ]
    Primary efficacy outcome: Number of Participants with Ischemic Stroke, Myocardial Infarction, or Death From Ischemic Vascular Causes
  • Major Hemorrhage [ Time Frame: Up to 90 days ]
    Primary safety outcome: Number of Participants with major hemorrhage
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2009)		 Major ischemic vascular events (ischemic stroke, myocardial infarction, and ischemic vascular death) [ Time Frame: 90 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
  • Ischemic Stroke [ Time Frame: Up to 90 days ]
    Secondary efficacy outcome:Number of participants with Ischemic stroke
  • Myocardial Infarction [ Time Frame: Up to 90 days ]
    Secondary efficacy outcome: Number of participants with Myocardial infarction
  • Death From Ischemic Vascular Causes [ Time Frame: Up to 90 days ]
    Secondary efficacy outcome: Number of participants with Death from ischemic vascular causes
  • Ischemic or Hemorrhagic Stroke [ Time Frame: 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 [ Time Frame: Up to 90 days ]
    Secondary efficacy outcome: Number of participants with ischemic stroke, myocardial infarction, death from ischemic vascular causes, or major hemorrhage
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2009)		 Secondary Composite Outcome Measure of ischemic stroke, MI, ischemic vascular death, major hemorrhage: This measure will incorporate benefits in terms of reduction in ischemic events with potential risks in terms of increased major hemorrhage [ Time Frame: 90 days ]
Current Other Pre-specified Outcome Measures
 (submitted: November 14, 2018)
  • Hemorrhagic Stroke [ Time Frame: up to 90 days ]
    Other safety outcome: Number of participants with Hemorrhagic stroke
  • Symptomatic Intracerebral Hemorrhage [ Time Frame: up to 90 days ]
    Other safety outcome: Number of participants with Symptomatic intracerebral hemorrhage
  • Other Symptomatic Intracranial Hemorrhage [ Time Frame: up to 90 days ]
    Other safety outcome: Number of participants with other symptomatic intracranial hemorrhage
  • Major Hemorrhage Other Than Intracranial Hemorrhage [ Time Frame: up to 90 days ]
    Other safety outcome: Number of Participants with Major hemorrhage other than intracranial hemorrhage
  • Minor Hemorrhage [ Time Frame: up to 90 days ]
    Other safety outcome:Number of Participants with Minor hemorrhage
  • Death From Any Cause [ Time Frame: up to 90 days ]
    Other safety outcome: Number of Participants with Death from any cause
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial
Official Title  ICMJE Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ischemic Attack, Transient
Intervention  ICMJE
  • Drug: Clopidogrel
    Loading dose of 600mg followed by 75 milligrams, oral, one tablet daily for 89 days
    Other Name: Plavix
  • Drug: placebo
    Loading dose of 8 tablets followed by one tablet daily for 89 days
Study Arms  ICMJE
  • Active Comparator: clopidogrel
    Patients assigned to clopidogrel in addition to aspirin
    Intervention: Drug: Clopidogrel
  • Placebo Comparator: placebo
    Patients assigned to placebo in addition to aspirin
    Intervention: Drug: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 14, 2018)		 4881
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2009)		 4150
Actual Study Completion Date  ICMJE April 9, 2018
Actual Primary Completion Date April 9, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Finland,   France,   Germany,   Mexico,   New Zealand,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00991029
Other Study ID Numbers  ICMJE 1U01S062835-01A1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University of California, San Francisco
Original Responsible Party S. Claiborne Johnston, MD, PhD, University of California, San Francisco
Current Study Sponsor  ICMJE University of California, San Francisco
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Neurological Emergencies Treatment Trials Network (NETT)
  • Medical University of South Carolina
  • The Emmes Company, LLC
Investigators  ICMJE
Principal Investigator: S. Claiborne Johnston, MD, PhD University of Texas, Austin
Principal Investigator: J. Donald Easton, MD University of California, San Francisco
Principal Investigator: Anthony S. Kim, MD, MAS University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP