Primary Objective: to determine if Apixaban is superior to placebo for preventing the composite of cardiovascular death, myocardial infarction, or ischemic stroke, in subjects with a recent acute coronary syndrome (ACS).
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary efficacy outcome: Time to first occurrence of cardiovascular death,
myocardial infarction, or ischemic stroke.
Primary safety outcome: Time to first occurrence of TIMI major bleeding.
Secondary outcome
Secondary efficacy outcomes: Time to first occurence:
• Cardiovascular death, myocardial infarction, unstable angina or ischemic
stroke.
• Cardiovascular death, fatal bleeding, myocardial infarction or stroke
(ischemic or hemorrhagic).
• Death (all-cause), myocardial infarction or stroke (ischemic or hemorrhagic).
Secondary safety outcome: Time to first occurrence of ISTH major bleeding.
Background summary
This trial studies extended oral anticoagulation in subjects with a recent
ST-segment elevation or non-ST-segment elevation ACS event. These patients have
recurrent ischemic events. Studies of the use of vitamin K antagonists after
ACS have demonstrated a significant reduction in recurrent ischemic events with
therapeutic anticoagulation (INR 2-3) compared to aspirine alone. Factor Xa
plays a pivotal role in blood coagulation. Apixaban is an orally active, direct
factor Xa inhibitor. Chronic oral anticoagulation with Apixaban in moderate to
high risk patients who have had a recent episode of ACS has the potential to
further reduce the frequency of major adverse cardiac events. The need for
alternative antithrombotic agents with acceptable risk-benefit rations for
chronic use in the ACS population is clear. Apixaban does not require
therapeutic monitoring and has a wide therapeutic index.
Study objective
Primary Objective: to determine if Apixaban is superior to placebo for
preventing the composite of cardiovascular death, myocardial infarction, or
ischemic stroke, in subjects with a recent acute coronary syndrome (ACS).
Study design
Appraise II will be a randomized, placebo-controlled, parallel arm superiority
study to evaluate the efficacy and safety of apixaban compared with placebo in
subjects with recent ACS and at least 2 additional risk factors for recurrent
ischemic events. Subjects will be randomized 1:1 to either apixaban 5 mg BID or
matching placebo following cessation of parenteral anticoagulation therapy.
Patients with a calculated creatinine clearance < 40 mL/min at the time of
randomization will receive apixaban 2.5 mg BID or matching placebo.
Randomization will be stratified by the investigator's intension to continue
single or dual antiplatelet therapy. The primary efficacy outcome will be the
composite of cardiovascular death, myocardial infarction or ischemic stroke.
The last randomized subject will be treated for a minimum of three months. All
randomized subjects will be followed until the targeted number of primary
events (938) occur in the study with one month post study-drug discontinuation
safety follow-up. The estimated study duration is approximately 28 months but
the final study duration will be determined by the time required to accrue 938
primary efficacy outcome events.
Intervention
Oral apixaban/placebo tablets 5 mg or 2.5 mg BID. After 938 primary events, the
last randomised patient will receive study medication for 3 months.
Study burden and risks
In case of participation of 28 months:
9 x ECG
9 x heart rate and blood pressure
1 x length and heigth
4 x blood drawn of 12.5 mL
Time of visits to the hospital and phone visits:
ca. 6 hours during 8 months
For woman of child-bearing potential, 8 pregancy tests will be performed
(urine).
Possible side effects of Apixaban are:
An increased risks of bleedings, nausea, obstipation, fever, vomiting,
swellings, joint pain, poor sleep, dizziness, xxx, rash, headache, fatigue,
stomach pain.
Chaussee de la Hulpe 185
1170 Brussels
België
Chaussee de la Hulpe 185
1170 Brussels
België
Listed location countries
Age
Inclusion criteria
1) An acute coronary syndrome within 7 days characterized by:
a) Symptoms of myocardial ischemia at rest lasting at least 10 minutes
And either
b) Elevation in cardiac biomarkers above the local upper limit of normal
Or
c) Dynamic ST-segment deviation (depression or elevation >= 0.1 mV (1.0 mm))
2) Completion of parenteral anticoagulation therapy for the index ACS event.
3) Clinically stable, receiving standard of care for ACS, including single or dual antiplatelet therapy, at the discretion of the treating physician.
4) Two or more of the following risk factors
a) Age >= 65 year
b) Diabetes mellitus
c) Prior myocardial infarction (other than the qualifying event) within 5 years
d) Ischemic cerebrovascular disease
e) Peripheral vascular disease (symptoms of claudication and/or peripheral revascularization, and/or ankle-brachial index (ABI) < 0.9)
f) Heart failure or left ventricular ejection fraction < 40% associated with the index ACS event
g) Impaired renal function (calculated CrCl < 60 mL/min)
h) No revascularization for index ACS event.
Exclusion criteria
1. Persistent severe hypertension (SBP * 180 mmHg of DB * 110 mmHg)
2. Calculated CrCl < 20 mL/min or on dialysis for end-stage renal disease
3. Active bleeding or high risk for major bleeding
4. Known coagulopathy
5. Acute pericarditis
6. Recent (<7 days) ischemic stroke
7. NYHA Class IV heart failure at time of randomization
8. Any history of intracranial bleeding
9. Active and/or significant, known hepatobiliary disease
10. Required ongoing treatment with a parenteral or chronic oral anticoagulant (eg, mechanical valve, recent DVT or pulmonary embolism, known left ventricular thrombus)
11. Required ongoing treatment with a strong inhibitor of CYP3A4, macrolide antibiotics, protease inhibitors.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-008298-77-NL |
| ClinicalTrials.gov | NCT00831441 |
| CCMO | NL27334.094.09 |