Objectives:The following objectives are designed to address the effects of SCH 530348 when administered orally in addition to the standard of care for a minimum of 1 year in subjects with documented atherosclerotic disease.Primary Objective: The…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Criteria for Evaluation:
All suspected efficacy and bleeding endpoints will be adjudicated by an
independent Clinical Events Committee that is blinded to treatment.
Primary Efficacy Endpoint:
The primary efficacy endpoint of the study is the first occurrence of any
component of the composite of cardiovascular death, MI, stroke, and urgent
coronary revascularization.
Key Secondary Efficacy Endpoint: The key secondary efficacy endpoint is the
first occurrence of any component of the composite of cardiovascular death, MI,
and stroke.
Secondary outcome
Other Secondary Endpoints Related to Efficacy:
Other secondary efficacy endpoints include the first occurrence of any
component of the following composites or individual components as indicated:
1. all-cause death, MI, stroke, and urgent coronary revascularization
2. cardiovascular death and MI
3. cardiovascular death, MI, stroke, urgent coronary revascularization, or
urgent hospitalization for vascular cause of ischemic nature
4. all-cause death, MI, stroke, any revascularization (including amputation for
ischemic limb)
5. cardiovascular death, MI, stroke, any revascularization (including
amputation for ischemic limb), or urgent hospitalization for vascular cause of
ischemic nature
6. the individual components of the composite primary efficacy endpoint
a. cardiovascular death
b. MI
c. stroke
d. urgent coronary revascularization
7. all-cause death
Exploratory Efficacy Endpoints:
These endpoints are not part of the objectives and are included to gather
information for future consideration. The exploratory efficacy endpoints
include any component of the following composites:
1. all-cause death, MI, and stroke in subjects undergoing PCI at any time
during participation in the study
2. all-cause death, MI, and stroke in subjects undergoing CABG at any time
during participation in the study
Other Secondary Endpoints Related to Safety: Safety endpoints included as part
of the objectives, in relative order of importance, comprise the incidences of
the following:
1. composite of moderate and severe bleeding events according to the GUSTO
classification
2. "clinically significant bleeding," defined as TIMI major or TIMI minor
bleeding, or bleeding that requires unplanned medical treatment, surgical
treatment, or laboratory evaluation even if it does not meet the criteria for
TIMI major or TIMI minor bleeding
Exploratory Safety Endpoints: These endpoints are not part of the objectives
and are included as additional ways to evaluate bleeding and to gather
information for future consideration
1. severe bleeding events according to the GUSTO criteria
2. all major and minor bleeding events, according to the TIMI classification
3. nonCABG TIMI major and minor bleeding events
4. bleeding events that do not meet the TIMI criteria for major or minor
5. in subjects undergoing CABG at any time while still receiving study drug
a. incidence of blood product transfusions (eg, red blood cell, platelet)
b. bleeding assessed (1) by chest-tube drainage (a) through 8 hours after
surgery and (b) total drainage, and (2) by need for reoperation for bleeding
Background summary
The benefit of antiplatelet agents in secondary prevention of atherothrombotic
events is well
established. The present trial is designed to determine whether inhibition of
the platelet PAR-1 receptor to
stimulation by thrombin in addition to standard-of-care antiplatelet therapy
(eg, aspirin, thienopyridines) can
result in further incremental benefit, as determined by reduction in the
incidence of atherothrombotic events
relative to standard of care alone, in subjects with established coronary
artery disease (CAD), cerebrovascular
disease (CVD), or peripheral artery disease (PAD).
Study objective
Objectives:
The following objectives are designed to address the effects of SCH 530348 when
administered orally in addition to the standard of care for a minimum of 1 year
in subjects with documented atherosclerotic disease.
Primary Objective:
The primary objective is to evaluate the hypothesis that SCH 530348 added to
standard of care will reduce the incidence of atherothrombotic ischemic events
relative to standard of care alone, as measured by the composite of
cardiovascular death, myocardial infarction (MI), stroke, and urgent coronary
revascularization.
Key Secondary Objective:
The key secondary objective is to evaluate clinical benefit with respect to the
composite of cardiovascular death, MI, and stroke.
Other Secondary Objectives Related to Efficacy: Other secondary efficacy
objectives will include evaluation of the incidence of the following composites
or individual components as indicated:
1. all-cause death, MI, stroke, and urgent coronary revascularization
2. cardiovascular death and MI
3. cardiovascular death, MI, stroke, urgent coronary revascularization, or
urgent hospitalization for vascular cause of ischemic nature
4. all-cause death, MI, stroke, any revascularization (including amputation for
ischemic limb)
5. cardiovascular death, MI, stroke, any revascularization (including
amputation for ischemic limb), or urgent hospitalization for vascular cause of
ischemic nature
6. the individual components of the composite primary efficacy endpoint
a. cardiovascular death
b. MI
c. stroke
d. urgent coronary revascularization
7. all-cause death
Other Secondary Objectives Related to Safety:
Specific safety objectives, in relative order of importance, include evaluation
of the incidences of the following:
1. composite of moderate and severe bleeding events according to the GUSTO
(Global Utilization of Streptokinase and Tissue Plasminogen Activator for
Occluded Arteries cooperative group) classification
2. "clinically significant bleeding," defined as TIMI (Thrombolysis in
Myocardial Infarction Study Group) major or TIMI minor bleeding, or bleeding
that requires unplanned medical treatment, surgical treatment, or laboratory
evaluation even if it does not meet the criteria for TIMI major or TIMI minor
bleeding
Study design
The study will be a multicenter, global, randomized, double-blind,
placebo-controlled, balanced-parallel-groups investigation of orally
administered SCH 530348 in the secondary prevention of ischemic events in men
and women at least 18 years old who have evidence or a history of
atherosclerosis involving the coronary, cerebral, or peripheral vascular
systems, to be conducted in conformance with Good Clinical Practice.
Following randomized treatment assignment and the beginning of dosing, subjects
will return after 30 days, 4, 8, and 12 months, and every 6 months thereafter
for scheduled efficacy/safety evaluations until the end of the study; that is,
when a statistically defined number of efficacy endpoint events have been
observed and every subject has participated in the study for at least 1 year.
Subjects who discontinue treatment for any reason will continue to be followed
by telephone contact for the occurrence of suspected efficacy endpoint and
bleeding events, and will be included in endpoint analyses.
Among the committees formed to oversee conduct of the study will be an
independent Data Safety Monitoring Board to protect further the rights, safety,
and well being of subjects who will be participating in this study by
monitoring the progress and results of the trial, and an independent Clinical
Events Committee to review and adjudicate each suspected efficacy and bleeding
endpoint event while blinded to treatment.
Intervention
Test Product, Dose, Mode of Administration:
SCH 530348 administered as the bisulfate salt (all references to "SCH 530348"
as a clinical test product imply "SCH 530348 bisulfate"). SCH 530348 oral 2.5
mg tablet taken once daily, with or without food.
Reference Therapy, Dose, Mode of Administration:
Placebo tablet to match SCH 530348 oral 2.5 mg tablet, taken as for SCH 530348.
Study burden and risks
The most frequently reported adverse events for SCH 530348 are zMild to
moderate hematoma and associated pain at venipuncture sites, and incidental
hematoma and bruising on extremities. Given the mechanism of action of the
drug, investigators should be watchful for bruising,
bleeding/hemorrhage/hematoma, thrombocytopenia, and neutropenia.
126 E. Lincoln Ave. PO Box 2000
Rahway 07065, NJ
US
126 E. Lincoln Ave. PO Box 2000
Rahway 07065, NJ
US
Listed location countries
Age
Inclusion criteria
1. Subject may be of either sex and any race, and must be at least 18 years old.;2. Subject must have evidence or a history of atherosclerosis involving the coronary, cerebral, or peripheral vascular systems as follows:
a.CAD as indicated by a history of presumed spontaneous MI (hospitalized with final diagnosis of MI, excluding periprocedural or definite secondary MI [eg, due to profound anemia or hypertensive emergency, troponin increase in sepsis]) 2 >= weeks but <= 12 months prior, or
b.ischemic (presumed thrombotic) CVD as indicated by a history of ischemic stroke (hospitalized with final diagnosis of nonhemorrhagic stroke) [includes completion of a standard evaluation for stroke in an acute care facility or stroke clinic without hospital admission] >= 2 weeks but <= 12 months prior, or
c. PAD as indicated by a history of intermittent claudication and
i. a resting ankle/brachial index (ABI) of <0.85, or
ii. amputation, peripheral bypass, or peripheral angioplasty of the extremities secondary to ischemia (note that enrollment of subjects entering with qualifying PAD will end when the total of the subset of subjects reaches ~15% of the planned total enrollment; investigators will be told when to stop enrollment of these subjects);3. Subject must be able and willing to give appropriate informed consent.;4. A woman of child-bearing potential who is currently sexually active must agree to use a medically accepted method of contraception prior to screening, while receiving protocol-specified medication, and for 2 months after stopping the medication.;5. A woman of child-bearing potential who is not currently sexually active must agree to use a medically accepted method of contraception should she become sexually active while participating in the study
Exclusion criteria
1. clinically unstable at the time of enrollment;2. any planned coronary revascularization or peripheral intervention;3. concurrent or anticipated treatment with warfarin (or derivatives, eg, phenprocoumon [but see notes in text for exceptions]), oral factor Xa inhibitor, or oral direct thrombin inhibitor after enrollment;4. concurrent or anticipated treatment with a potent inducer (eg, rifampin) or potent inhibitor (eg, ketoconazole, erythromycin) of CYP3A4 isoenzymes (but see note in text for exceptions);5. history of a bleeding diathesis, or evidence of active abnormal bleeding within 30 days before enrollment;6. history at any time of intracranial hemorrhage (except "microhemorrhage" [eg, as detected on T2-weighted MRI]), intracranial or spinal cord surgery, or a central nervous system tumor or aneurysm;7. documented sustained severe hypertension (systolic blood pressure >200 mmHg or diastolic blood pressure >110 mmHg) at enrollment or within the previous 10 days;8. severe valvular heart disease, as defined by the American College of Cardiology/American Heart Association;9. history within 2 weeks prior to enrollment of major surgery other than mentioned above or of ischemic (presumed thrombotic) stroke;10. known platelet count <100,000/mm3 within 30 days before enrollment;11. known active hepatobiliary disease, or known unexplained persistent increase in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) activity to two times or more the upper limit of the reference range (upper limit of "normal" [>=2xULN]);12. any serious illness or any condition that the investigator feels would (a) pose a significant hazard to the subject if investigational therapy were initiated, or (b) would limit the prognosis of the subject, regardless of investigational therapy;13. any serious medical comorbidity (eg, active malignancy) such that the subject's life expectancy is <24 months;14. previous participation in the current study;15. current participation in any other study of investigational therapy, or participation in such a study within the last 30 days;16. known hypersensitivity to any component of the current investigational product;17. subject is a woman who is breast-feeding, pregnant, or who intends to become pregnant;18. subject is part of the staff personnel directly involved with this study, or is a family member of the investigational staff;19. Known current substance abuse at the time of enrollment
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 | EUCTR2006-002942-12-NL |
| ClinicalTrials.gov | NCT00526474 |
| CCMO | NL19068.003.07 |