Key Dates

None

National Heart, Lung, and Blood Institute (NHLBI)

The National Heart, Lung, and Blood Institute (NHLBI) intends to publish a Request for Applications (RFA) seeking applications for a multisite clinical trial that will test a screening approach to identify coronary atherosclerosis and test interventions to reduce the progression of coronary atherosclerosis. There will be only one award for this RFA. The planned RFA will utilize the UG3/UH3 activity code with details provided below.

The planned RFA will support a Clinical Coordinating Center (CCC) and will run in parallel with a companion RFA for a collaborating Data Coordinating Center (DCC) application. This RFA will accept only an application that is part of a collaborative pair of applications. The pair must include one application to the CCC UG3/UH3 Notice of Funding Opportunity (NOFO) plus one application to the companion DCC U24 NOFO. Both a CCC application and a collaborating DCC application must be submitted on the same due date for consideration by NHLBI. CCC (UG3/UH3) applications submitted without a collaborative DCC (U24) application will be deemed incomplete and will not proceed to review.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. The planned RFAs are expected to be published in Summer 2024 with an expected application due date in Fall 2024.

Trial participants will be young adults under the age of fifty who are at low or borderline 10-year risk (< 7.5%) for their first atherosclerotic cardiovascular disease (ASCVD) event, yet at high lifetime risk of developing cardiovascular disease (CVD). The long-range goal of this research strategy is to determine if earlier treatment of subclinical atherosclerosis prevents more CVD than current guideline-recommended treatment. The hypothesis to be tested with this clinical trial is that earlier intervention of subclinical atherosclerosis will halt or reverse progression of coronary atherosclerosis plaques before any clinical events have occurred.

A critical gap to be addressed by this clinical trial is to first determine if and how early coronary atherosclerotic plaque can be successfully treated to halt or reverse progression and development into at-risk plaques that can lead to cardiovascular events. The demonstration that the progression of coronary atherosclerotic plaques can be successfully slowed or halted in high-risk individuals has the potential to change clinical guidelines and lead to change in clinical practice. Rather than using a clinical biomarker as a surrogate outcome, such as LDL-cholesterol, this trial will directly quantify subclinical coronary artery atherosclerotic disease.

The planned opportunity will support a primary prevention clinical trial with two sequential components. The first component will develop an efficient screening approach to identify the appropriate population eligible for the enrollment in the intervention (the second component of the trial). The screening component will begin in the UG3 phase, and if successful, will continue during the UH3 phase until the trial is completely enrolled. The intervention component of the trial will commence during the UH3 phase and will determine which intervention(s) are most efficacious at reducing the onset or slowing the progression of subclinical coronary atherosclerosis. It is expected that the trial will have up to three treatment arms. One will be a control or comparison arm, and the second and the third arms will test pharmacologic interventions. The control arm is expected to be the current guideline-based standard of care practices. One of the two intervention arms is expected to involve pharmacological intervention(s) with well-established trial evidence of efficacy for primary prevention in older, high-risk adults such as or LDL-lowering therapy, and the other arm may involve intervention(s) with less definitive trial evidence of primary prevention or secondary prevention efficacy. Each arm may have a single or combined intervention. The second or third arm may include a behavioral intervention if it has trial evidence reducing of CVD clinical events in high-risk adults. The primary outcome of the intervention component will be a non-invasive measurement of coronary artery atherosclerosis which is strongly associated with myocardial infarctions and other CVD clinical events. The trial should be designed to have a high level of statistical power (> 85%) to detect a halt or meaningful reduction in early coronary atherosclerosis during the trial. Applicants will need to specify the proportion of trial participants with evidence of subclinical coronary atherosclerosis at baseline.

There will be key milestones for the UG3 and UH3 phases of the trial. Key milestones for the UG3 phase must be achieved prior to successful funding of the subsequent phase of the trial (UH3). TheUG3 phase should establish the feasibility and the success of the screening component. It should also demonstrate the high likelihood of completing the recruitment of trial participants in the intervention component by the end of the first year of the UH3 phase and completion of the intervention follow-up by the end of the fourth year of the UH3 phase. The applicant should propose key milestones for the UH3 phase that measure the progress at achieving the operational and scientific goals of this intended NOFO.

This Notice encourages investigators with expertise and insights into this area of subclinical atherosclerosis to begin to consider applying for this new RFA.

NHLBI expects applicants  to recruit  individuals from diverse backgrounds, including individuals from underrepresented groups for participation in the study team.  See  NIH’s Notice of Interest in Diversity. NHLBI supports the inclusion of early-stage investigators as a part of study teams. Collaborative investigators combining expertise in multisite clinical trials, CVD risk assessment, primary prevention, and non-invasive coronary imaging will be encouraged. Applicants to the DCC NOFO will additionally bring skills, experience, and capability in multidisciplinary DCC functions including coordination, tracking, logistics and administration, communications, data management, regulatory support, and biostatistical/analytical support to successfully conduct the project to completion. 

Funding Information

Applications are not being solicited at this time. 

Inquiries

Please direct all inquiries to:

Lawrence Fine M.D., DrPH
National Heart, Lung, and Blood Institute (NHLBI) 
Division of Cardiovascular Sciences 
[email protected]

David Schopfer, M.D., M.A.S.
National Heart, Lung, and Blood Institute (NHLBI) 
Division of Cardiovascular Sciences 
[email protected]