ST Monitoring to Detect ACS Events in ICD Patients
This is a prospective, non-randomized, multicenter, pivotal IDE study. The intent of this
study is to demonstrate the safety and effectiveness of the ST Monitoring Feature in the
Fortify® ST, Fortify Assura® ST, and Ellipse® ST family of devices, as well as any future St
Jude Medical devices with the same ST Monitoring Feature capabilities. Effectiveness of the
device will be evaluated by analyzing the sensitivity of the ST Monitoring Feature to detect
clinical events. In addition, safety of the ST Monitoring Feature will be evaluated by
demonstrating a low percentage of patients with false positive events.
Active, not recruiting | Atherosclerosis | Multisite
Nattokinase Atherothrombotic Prevention Study
Objectives and Hypotheses: The goal of the proposed study is to determine under randomized
controlled trial (RCT) conditions whether nattokinase reduces subclinical atherosclerosis
and cognitive decline in healthy women and men. The investigators' hypotheses are: 1)
Compared to placebo, nattokinase will show less subclinical atherosclerosis progression and
cognitive decline in healthy women and men; 2) The reduction in subclinical atherosclerosis
progression and cognitive decline with nattokinase will be correlated; and, 3) The reduction
in progression of subclinical atherosclerosis and cognitive decline with nattokinase will be
mediated through hemostatic, fibrinolytic and hemorheological factors as well as attenuation
of inflammation, monocyte activation, vascular endothelium injury and activation of vascular
endothelium by circulating monocytes.
Specific Aims: To conduct a RCT to determine the effect of nattokinase on the progression of
subclinical atherosclerosis (primary trial end point) and cognitive decline (secondary trial
end point). Healthy non-demented women and men >55 years old without pre-existing
symptomatic CVD and diabetes mellitus will be randomized over a 2 year period to oral
nattokinase (2,000 fibrinolysis units) daily versus placebo in this double-blind,
placebo-controlled trial; randomized treatment will be 3-years. The following 5 major
specific aims will be completed:
1. To determine the effect of nattokinase on the progression of subclinical carotid artery
atherosclerosis determined as the rate of change of the common carotid artery
intima-media thickness (CIMT) and arterial stiffness in computer image processed B-mode
ultrasonograms.
2. To determine the effect of nattokinase on cognitive decline determined with a
neuropsychological battery designed to evaluate 7 cognitive domains including:
attention, concentration, working memory, executive function;
visuospatial/visuoconstructive skills; naming/semantic memory; and verbal and nonverbal
episodic memory.
2a. To determine the effect of nattokinase on cognitive decline according to apolipoprotein
(Apo) E e4 genotype.
3. To determine the association of subclinical atherosclerosis progression with cognitive
decline.
4. To determine whether the effects of nattokinase on subclinical atherosclerosis and
cognitive decline are mediated through hemostatic (fibrinogen, factor VIII, platelet
activity), fibrinolytic (tPA, PAI-1, D-dimer), hemorheological (plasma and blood viscosity,
red blood cell aggregation) and inflammatory (MCP-1, IL-8, TNFα, IL-1β, IL-10, monocyte cell
surface markers CD11b/CD11c and VLA-4, expression of adhesion molecules VCAM-1 and ICAM-1 in
cultured human aortic endothelial cells) factors as well as blood pressure.
Not yet recruiting | Atherosclerosis | Not Multisite
International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA)
BACKGROUND:
Evidence supporting a routine invasive practice paradigm for patients with stable ischemic
heart disease (SIHD) is outdated. In strategy trials conducted in the 1970s, coronary artery
bypass grafting (CABG) improved survival as compared with no CABG in SIHD patients with
high-risk anatomic features. The relevance of these studies today is speculative because
contemporary secondary prevention—aspirin, beta-blockers, statins, ACE inhibitors, and
lifestyle interventions—were used minimally if at all. Subsequent trials have compared
percutaneous coronary intervention (PCI) with medical therapy, as PCI has replaced CABG as
the dominant method of revascularization for SIHD. To date, PCI has not been shown to reduce
death or myocardial infarction (MI) compared with medical therapy in SIHD patients.
COURAGE and BARI 2D, the two largest trials comparing coronary revascularization vs. medical
therapy in SIHD patients, found that among patients selected on the basis of coronary
anatomy after cath, an initial management strategy of coronary revascularization (PCI, PCI
or CABG, respectively) did not reduce the primary endpoints of death or MI (COURAGE), or
death (BARI 2D) compared with OMT alone. These data suggest, but do not prove, that routine
cath--which often leads to ad hoc PCI through the diagnostic-therapeutic cascade--may not be
required in SIHD patients. However, most patients enrolled in COURAGE and BARI 2D who had
ischemia level documented at baseline had only mild or moderate ischemia, leaving open the
question of the appropriate role of cath and revascularization among higher risk patients
with more severe ischemia. Observational data suggest that revascularization of patients
with moderate-to-severe ischemia is associated with a lower mortality than medical therapy
alone, but such data cannot establish a cause and effect relationship. In clinical practice
only about half such patients are referred for cath, indicating equipoise. Furthermore,
analysis of outcomes for 468 COURAGE patients with moderate-to-severe ischemia at baseline
did not reveal a benefit from PCI. This issue cannot be resolved using available data
because all prior SIHD strategy trials enrolled patients after cath, introducing undefined
selection biases (e.g., highest risk patients not enrolled) and making translation of study
results problematic for clinicians managing patients who have not yet had cath.
A clinical trial in SIHD patients uniformly at higher risk (which could not have been
performed before COURAGE and BARI 2D results were available) is needed to inform optimal
management for such patients.
DESIGN NARRATIVE:
The study protocol is final, and was distributed to sites February 2012. Study protocol v2.0
was approved in January 2014.
PARTICIPATING COUNTRIES:
North America
- Canada
- Mexico
- USA (~150 sites)
South America
- Argentina
- Brazil
- Chile
- Peru
Asia
- China
- India
- Japan
- Singapore
- Taiwan
- Thailand
- Russian Federation
Pacifica
- Australia
- New Zealand
Europe
- Austria
- Belgium
- Denmark
- France
- Germany
- Hungary
- Italy
- Lithuania
- Macedonia
- Netherlands
- Poland
- Portugal
- Romania
- Serbia
- Spain
- Sweden
- UK
Middle East
- Israel
- Saudi Arabia
- Turkey