Troponin I (cTnI) is a protein that is found in the heart muscle. When someone has a heart attack or other injury to the heart muscle, increased levels of cTnI can be measured in the blood and testing for cTnI in blood is used to help diagnose a heart attack and other heart conditions.

Troponin I (cTnI) is a protein that is found in the heart muscle. When someone has a heart attack or other injury to the heart muscle, increased levels of cTnI can be measured in the blood and testing for cTnI in blood is used to help diagnose a heart attack and other heart conditions.

Acute coronary syndrome is a life-threatening condition, which most commonly occurs when an atherosclerotic plaque ruptures or erodes, leading to thrombus formation within a coronary artery. A thrombus within a coronary artery can result in unstable angina, MI, or sudden death. Even after recovery from an acute episode of ACS, patients continue to be at heightened risk. The risk of recurrent CV events is high despite advances in medical therapy and standard therapeutic
regimens that have produced important improvements in the prognosis of patients with MI.
CSL112 is a novel formulation of apoA-I, the major functional component of high-density lipoprotein. It is purified from human plasma, formulated to deliver exogenous apoA-I. Apolipoprotein A-I is formulated with phosphatidylcholine (PC) and stabilized with sucrose and cholate as excipients. CSL112 is being developed for use in patients with ACS (diagnosed with either STEMI or NSTEMI) to reduce the risk of CV death, MI, and stroke upon delivery of CSL112. Evidence from the Apo-I Event Reducing in Ischemic Syndromes-I (AEGIS-I) study has demonstrated that administration of apoA-I increases cholesterol efflux in MI patients.
This is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to evaluate the efficacy and safety of CSL112 on reducing the risk of major adverse CV events (MACE) in subjects with ACS (diagnosed with STEMI or NSTEMI), who are receiving evidence-based medical therapy.
Subjects will be randomized 1:1 to 1 of 2 treatment groups (CSL1126 g or placebo). Randomization at baseline will be stratified by subjects' index MI type (STEMI vs NSTEMI), management of the index MI (PCI vs medically managed), and region (North America, Latin America, Western Europe, Central and Eastern Europe, or Asia Pacific). The study will consist of a Screening Period, an Active
Treatment Period, and a Follow-up Period. Investigational product will be administered by intravenous (IV) infusion once weekly for 4 consecutive weeks. The primary efficacy outcome will be the composite of CV death, MI, or stroke from time of randomization through 90 days. Adverse event monitoring will continue through Visit 8 (Day 90), and all serious adverse events will be collected
through the end of the study, regardless of relationship to investigational product. Subjects will be followed for occurrence of MACE for 365 days from randomization.

COORDINATE-Diabetes is a cluster-randomized clinical trial to test the effectiveness of an innovative, clinic-level educational intervention to improve the management of patients with T2DM and CVD. The trial will be performed and interpreted in the context of clinical diabetes care in the U.S. using data from select electronic health record (EHR) sites. A subset of sites with EHR data available for querying in existing datamarts will be recruited to participate in two EHRfocused objectives: 1) to perform a baseline characterization of patients with T2DM and CVD, including demographics, treatment patterns and healthcare utilization such as hospitalization; and 2) to assist with the identification of patients eligible for the educational intervention trial.

Current care patterns for patients with acute chest pain fail to provide optimal quality and value. To avoid missing acute
coronary syndrome (ACS), emergency physicians hospitalize >50% of patients who present to the Emergency Department with
chest pain. However, <10% are ultimately diagnosed with ACS, and this pervasive overtriage
costs $1013
billion annually.
The HEART Pathway, which was developed at Wake Forest Baptist Health (WFBH), is designed to improve care for patients with
chest pain. It uses a validated clinical decision aid and serial troponin measures to provide realtime
decision support to providers.
In our prior studies, the HEART Pathway decreased hospitalizations, stress testing, and hospital length of stay, without
increasing adverse events. These studies led to a learning health system project in collaboration with insurers, in which the
HEART Pathway was fully integrated into the WFBH EHR. Preliminary results demonstrate further reductions in hospitalizations
and stress testing. Given WFBH's success with the HEART Pathway, the next logical step is regional dissemination.
This project will leverage Carolinas Collaborative infrastructure to collect data specific to the HEART Pathway from all 4 health
systems, establishing rates of healthcare utilization and ACS outcomes for Emergency Department patients with chest pain in
the Carolinas. In addition, we will engage key stakeholders at each health system to develop an implementation strategy. This
proposal builds on our prior work and will provide pilot data essential for a larger grant application that will support rigorous
testing and implementation of the HEART Pathway across Carolinas Collaborative health systems.