Clinical Trial Details
— Status: Withdrawn
Administrative data
NCT number |
NCT02144831 |
Other study ID # |
MENA-TIA study |
Secondary ID |
|
Status |
Withdrawn |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
July 2014 |
Est. completion date |
October 2018 |
Study information
Verified date |
May 2022 |
Source |
University of Alberta |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The primary goal of the research is to determine if 10 days of dual anti-platelet treatment
is as effective as 30 days of similar treatment in the prevention of stroke, myocardial
ischemia (MI) and death in patients with TIAs and minor stroke.
Description:
Transient Ischemic Attacks (TIAs) are common, easily misdiagnosed, not investigated
appropriately and are often harbingers of disabling strokes. A TIA is best defined as an
episode of neurological dysfunction caused by focal ischemia that lasts for less than 24
hours (very often less than an hour). Minor stroke (NIHSS of <3) is often lumped together
with TIAs. The distinction between minor ischemic stroke and TIA is unimportant in terms of
prognosis. Numerous studies have shown that short-term risk of stroke is high after TIA and
minor ischemic stroke, particularly in the first few days, even in patients treated with
aspirin, the current standard of care. In patients with TIAs and minor stroke effective
therapies can significantly reduce the overall burden of stroke if initiated immediately. The
recently completed CHANCE study comprising more than 5000 patients with TIAs and minor stroke
showed that a short course of combination antiplatelet medications (ASA+clopidogrel) for 3
weeks significantly reduced the 90-day risk of stroke when compared to ASA treatment.
There are three trials where patients with TIAs and minor strokes were treated early after
onset of symptoms with combination treatment with clopidogrel and ASA versus ASA alone.
FASTER was a pilot trial based in Canada (5). It evaluated clopidogrel (300 mg load and 75
mg/day afterwards) on a background of aspirin in patients presenting within 24 hours of a TIA
or minor stroke. The trial enrolled 392 patients. The risk of stroke (ischemic or
hemorrhagic) at 90 days was 11% in those treated with aspirin alone and 7% in those treated
with clopidogrel and aspirin, a non-significant 36% relative risk reduction (RRR) in this
pilot trial (p=0.19). There were two Intra cerebral hemorrhages(ICHs) and these were both in
patients treated with clopidogrel and ASA.
The recently completed CHANCE trial (5170 patients enrolled within 24 hours of symptom-onset)
from China showed that in patients with high-risk TIAs and minor strokes, there was a
significant absolute reduction of early stroke at 90 days from 11.7 % to 8.2 % hazard ration
(HR) 0.68, 95% Confidence interval (CI) 0.57-0.81; p<0.001) in patients treated with a
combination of ASA and clopidogrel for 21 days compared to ASA alone (13). Similar to the
EXPRESS study (3), most of the strokes developed in the initial days following the TIA. The
observation that strokes occur very early, as is evident from EXPRESS and CHANCE suggests
that perhaps the vascular pathology responsible for the events begins to heal rapidly once
antiplatelet therapy is initiated. This allows for the possibility that shorter duration
combination antiplatelet therapy may also be as effective as the 21 days treatment in CHANCE
or the 30 days treatment in the NIH funded POINT trial. A prospective study that compares the
outcome of stroke, MI or death at 90 days in patients treated with 10 days or 30 days of dual
antiplatelet therapy will therefore be very useful. If the shorter duration dual antiplatelet
therapy is as effective as the longer duration dual antiplatelet treatment, this will result
in lower costs and the lower risk of side effects in stroke prevention in high-risk TIA
patients.
Hypothesis:
The short duration use of dual antiplatelet agents for 10 days is as effective as a longer
duration of 30 days or longer. The shorter duration treatment will however result in fewer
hemorrhagic complications.
STUDY OBJECTIVES
The Primary Specific Aim of this randomized, multicenter clinical trial is to determine
whether a 10 day course of treatment with clopidogrel 75 mg/day by mouth after a loading dose
of 600 mg is as effective a similar treatment for 30 days in improving survival free from
ischemic vascular events (ischemic stroke, myocardial infarction, and ischemic vascular
death) at 90 days when subjects are randomized within 24 hours of time last known free of new
ischemic symptoms in patients receiving aspirin 50-325 mg/day as the long-term antiplatelet
therapy.
There will be several secondary aims of the study, including comparison of the risk of major
and minor hemorrhage, the risk of recurrent TIAs or minor stroke at 10-day, 30-day and 90-day
evaluations and the measuring severity of any stroke in the two arms in the 90 days of
follow-up. The NIHSS will be used for assessment of the severity of the stroke.
Participation Centers During the course of the trial, approximately 10-15 sites will enroll
approximately 1200 subjects with TIA or minor ischemic stroke. Before enrolling subjects into
the study, all collaborating sites will obtain approval from local institutional review
boards (IRBs), which will have access to all study documentation and educational materials.
Study Population The study will include both TIA and minor ischemic stroke. Neurological
impairment at the time of enrollment is expected to be minimal since the deficits prompting
diagnosis will have largely resolved. Vascular risk factors, including diabetes,
hypertension, and coronary artery disease, are expected to be common.
Pregnant women will be excluded from the study because the safety of clopidogrel is not
established in this population, and this drug may increase risk of harm to the fetus. Women
at risk for pregnancy (see Exclusion Criteria) will also be excluded. No other vulnerable
population will be excluded from the study.
TREATMENTS Study Drugs This randomized study is primarily designed to compare a
clopidogrel/aspirin combination versus an aspirin alone regimen for 10 days versus 30 days.
This is an open-label design. Patients and physicians will be aware of the study medications.
Aspirin tablets will be open label with the dose in a range 50-325 mg daily determined by the
treating physician. A dose of 162 mg daily x 5 days, followed by 81 mg daily will be strongly
recommended.
Clopidogrel treatment will be offered in the following manner:
Day 1: 8 tablets of clopidogrel 75 mg (loading dose of 600 mg) From D2 to D10 or D2 to D30:
one tablet of clopidogrel 75 mg
All patients will be on ASA 50-325 for the 90 days until the final assessment. Assignment to
a Treatment Group The randomization will take place locally. To keep the study simple,
sequential subjects will be randomized to 10 days (even number recruitment) and 30 day (odd
number recruitment). All centers will recruit competitively into the trial.