UG3HL181434

1/2 Preempt: Prospective randomized evaluation and management of premature atherosclerosis - failure to detect and treat atherosclerosis in younger adults worsens cardiovascular morbidity and mortality.

Current strategies of assigning preventive therapies are not based on screening for atherosclerosis, but rather on short-term risk scores that heavily weight age and leave most at-risk young and middle-aged adults untreated.

A new paradigm of screening for and identifying subclinical atherosclerosis via coronary computed tomography angiography (CCTA) is emerging because subclinical atherosclerosis has prognostic superiority over traditional risk scores.

However, it is still unknown how best to screen for and identify younger adults who have subclinical coronary atherosclerosis, and how best to treat them to reduce atherosclerotic burden.

Both LDL-C and inflammation are causal in the pathogenesis of atherosclerosis, but it is unknown whether treating either or both processes in younger individuals can effectively and safely reduce atherosclerotic burden.

The PREEMPT (Prospective Randomized Trial of the Evaluation and Management of Premature Atherosclerosis) study will address this urgent public health need by determining optimal strategies to screen for, identify, and treat subclinical coronary atherosclerosis in young and middle-aged adults.

Aim 1 will focus on screening younger adults for subclinical coronary atherosclerosis.

We will evaluate the effectiveness of three strategies to detect coronary atherosclerosis in young and middle-aged adults (women aged 40−60 and men aged 30−50) at low 10-year, but high lifetime risk.

These strategies will include an electronic health record search, outreach to family members of those with premature heart disease, and community outreach/social media.

The outcome will be proportion screened with coronary artery calcium (CAC) score >0.

An adaptive design will be utilized to modify or eliminate ineffective strategies.

Aims 2 and 3 will focus on assessing the efficacy and safety/tolerability of 3 therapeutic strategies to reduce atherosclerotic burden.

Individuals who meet clinical eligibility criteria through the screening study, or opportunistically through preexisting imaging evidence of coronary calcification, and have a CAC score of 1−99 will undergo CCTA to confirm presence of measurable non-calcified plaque (NCP) volume, and will then be randomized to a placebo-controlled, double-masked, 2x2 factorial randomized trial of rosuvastatin 20mg, colchicine 0.5mg, or the combination vs. placebo.

All participants will also receive a state-of-the-art mHealth behavioral intervention to ensure lifestyle modification for all participants.

The primary endpoint will be centrally adjudicated NCP volume on CCTA at 2 years, adjusting for baseline NCP volume.

If successful, PREEMPT will reduce the unacceptably high morbidity and mortality of cardiovascular disease by providing randomized trial evidence supporting a paradigm shift away from a 10-year risk-based prevention strategy and towards earlier detection and treatment of subclinical atherosclerosis in younger adults.

Duke University

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Durham, North Carolina 277012183 United States

Single Zip Code

Phased Multi-Site Clinical Trial: Testing Prevention of Cardiovascular Disease in Young Adults With High Lifetime Risk Using Surrogate Outcomes - Clinical Coordinating Center (Collaborative UG3/UH3 Clinical Trial Required) (RFA-HL-25-010)

Amendment Since initial award the End Date has been shortened from 06/30/32 to 06/30/27.