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A Randomized Comparison of Stage-Based Care Versus Risk Factor-Based Care for Prevention of Cardiovascular Events

Not Applicable
Recruiting
Conditions
Diabetes Mellitus, Type 2
Metabolic Syndrome
PreDiabetes
Interventions
Device: The Cleerly CAD Staging System
Registration Number
NCT06112418
Lead Sponsor
Cleerly, Inc.
Brief Summary

TRANSFORM is a prospective, randomized, open blinded endpoint (PROBE), event-driven, pragmatic trial in patients who are at increased risk for atherosclerotic cardiovascular (CV) disease but with no known symptomatic CV disease. The trial tests the hypothesis that a Cleerly Coronary Artery Disease (CAD) Staging System-based care strategy reduces CV events compared with risk factor-based care.

Detailed Description

Cardiovascular disease (CVD) persists as the leading cause of morbidity and mortality worldwide at high societal cost. The current primary CVD prevention strategy relies upon risk stratification using population health markers such as age, sex, diabetes, hypertension, dyslipidemia and tobacco use, with preventive therapy intensified in higher risk strata. Since these risk factors are indirect surrogate markers of the underlying disease, atherosclerosis, this strategy leads to treatment of individuals with risk factors who do not have atherosclerosis and failure to treat those with significant atherosclerosis who lack risk factors. The current strategy also cannot determine which individuals are inadequately treated despite effective risk factor management (residual risk). With the current approach, the CV death rate is trending upward in the US despite evidence that screening asymptomatic patients reduces CV events and the widespread availability of effective preventive therapies.

This randomized, controlled, pragmatic trial is designed to address the unmet need for better strategies to identify asymptomatic individuals at increased risk for CV events due to atherosclerosis and to personalize their treatment based on CV risk estimates using coronary artery disease (CAD) visualization and quantification.

This study enrolls patients without known symptoms of ASCVD but who are at increased risk for ASCVD due to their age and having diabetes, prediabetes or metabolic syndrome and tests the hypothesis that a CAD Staging System-based care strategy reduces CV events compared with risk factor-based care. The Cleerly CAD Staging System incorporates imaging-based evaluation for coronary atherosclerosis, algorithm-supported pharmacotherapy and personalized education about their CAD.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
7500
Inclusion Criteria
  1. Provided electronic or written informed consent

  2. Men > 55, women > 65 years of age

  3. Type 2 diabetes mellitus requiring pharmacologic therapy, prediabetes (most recent HbA1c 5.7 to 6.4% and/or fasting glucose 100-125 mg/dL [5.6-6.9 mmol/L]) and/or metabolic syndrome. Metabolic syndrome is defined as > 3 of the following criteria (International Diabetes Federation 2006):

    • Body mass index ≥ 27 kg/m2 or abnormal waist circumference defined as ≥ 80 cm (31.5 inches) for women, ≥ 94 cm (37 inches) for men; for South and East Asian men (e.g., Asian Indian, Chinese, Japanese) ≥ 90 cm (35.4 inches)
    • Fasting triglycerides ≥ 150 mg/dL (1.7 mmol/L) or treated hypertriglyceridemia
    • HDL-cholesterol (HDL-C) < 40 mg/dL (1.03 mmol/L) in men, <50 mg/dL (1.29 mmol/L) in women or treatment for this lipid abnormality
    • Systolic blood pressure (BP) ≥ 130 and/or diastolic BP≥ 85 mm Hg and/or treated hypertension
    • Fasting blood glucose ≥ 100 mg/dL (5.6 mmol/L) or HbA1c ≥ 5.7%
  4. Have a device (e.g., smartphone, tablet, computer) for communication with the central cardiologist-led team managing drug treatment for the personalized care group

Exclusion Criteria
  1. History of symptomatic CVD defined as prior MI, exertional or unstable angina, ischemic stroke, claudication, arterial revascularization for atherosclerosis or other CVD being actively managed by a cardiologist, e.g. atrial fibrillation, heart failure

  2. Planned arterial revascularization

  3. Inability to complete screening CCTA or any condition that would increase the risk associated with CCTA or increase likelihood of uninterpretable scan including:

    1. eGFR < 60 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) or Modification of Diet in Renal Disease (MDRD) equation (www.kidney.org/professionals/kdoqi/gfr_calculator)
    2. Allergy to iodinated contrast or history of contrast-induced nephropathy (including adverse reaction to contrast at screening CCTA) or screening laboratory values consistent with untreated hyperthyroidism. Participants with elevated thyroid-stimulating hormone (TSH) may be enrolled but should be referred to their physician for evaluation for treatment.
    3. Thyroid cancer in the previous five (5) years or planned radioactive iodine treatment
    4. Weight > 300 lbs. (136 kg) or above manufacturer-recommended limit for scanner and table at the site
    5. Inability to hold breath for > 10 seconds
    6. Active arrhythmia (atrial fibrillation, atrial flutter, frequent premature atrial, or ventricular contractions) with poorly controlled rate (i.e., > 80 beats per minute at screening or prior to CCTA)
    7. Contraindication to dosing with beta blocker or nitroglycerin on day of screening CCTA
    8. Any other factor that, in the opinion of the investigator, would increase participant risk or increase the chance of an uninterpretable CCTA
  4. Unsuitable as a trial participant in the opinion of the investigator for reasons including significant left main stenosis (e.g. ≥ 70%; site will be notified by Cleerly), other health condition with life expectancy < 3 years or being at risk of poor compliance with study procedures (e.g., active substance abuse or untreated mental illness that, in the opinion of the investigator, is likely to adversely affect adherence or retention)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cleerly Stage-Based CareThe Cleerly CAD Staging SystemThe Cleerly Stage-Based Care group will receive personalized care centrally managed by a remote cardiologist-led team. They will also receive an initial pre-randomization assessment of current treatment by a centralized cardiology team to optimize care relative to primary prevention guidelines. Cleerly CAD Staging System results will be discussed with participants and serve as the basis for standardized algorithm-supported pharmacotherapy \& education, which will be intensified if plaque burden has progressed at 24 months.
Primary Outcome Measures
NameTimeMethod
The primary objective is to compare Cleerly stage-based care with risk factor-based care on the risk of CV events.Through study completion- an average of 3.5 years

The primary endpoint is total (first and subsequent) events for the composite endpoint of CV death, myocardial infarction (MI), ischemic stroke, acute limb ischemia, clinically driven arterial revascularization, and hospitalization or urgent visit for heart failure.

Secondary Outcome Measures
NameTimeMethod
The secondary objective is to compare Cleerly CAD stage-based care with risk factor-based care on other clinical events of CV and renal morbidity and mortality.Through study completion- an average of 3.5 years

The secondary endpoints are time from randomization to all-cause death.

Trial Locations

Locations (82)

Chandler Clinical Trials

🇺🇸

Chandler, Arizona, United States

Scottsdale Clinical Trials

🇺🇸

Scottsdale, Arizona, United States

Sun City Research

🇺🇸

Sun City, Arizona, United States

Noble Clinical Research

🇺🇸

Tucson, Arizona, United States

Cardiovascular Research Foundation of Southern California

🇺🇸

Beverly Hills, California, United States

Amicis Research: Beverly Hills

🇺🇸

Beverly Hills, California, United States

Valiance Clinical Research - Canoga Park

🇺🇸

Canoga Park, California, United States

Cardiovascular Institute of San Diego

🇺🇸

Chula Vista, California, United States

Amicis Research: Granada Hills

🇺🇸

Granada Hills, California, United States

Valiance Clinical Research: Huntington Park

🇺🇸

Huntington Park, California, United States

Long Beach Research Institute

🇺🇸

Long Beach, California, United States

Amicis Research: Newhall

🇺🇸

Newhall, California, United States

Ace Research Institute: Northridge

🇺🇸

Northridge, California, United States

Amicis Research: Northridge

🇺🇸

Northridge, California, United States

Ace Research Institute: Northridge #2

🇺🇸

Northridge, California, United States

Northridge Clinical Trials

🇺🇸

Northridge, California, United States

Amicis Research: San Fernando

🇺🇸

San Fernando, California, United States

Valiance Clinical Research - Tarzana

🇺🇸

Tarzana, California, United States

Lundquist Institute for Biomedical Innovation at Harbor - UCLA Medical Center

🇺🇸

Torrance, California, United States

Amicis Research: Valencia

🇺🇸

Valencia, California, United States

University of Colorado

🇺🇸

Aurora, Colorado, United States

St. Josephs (Intermountain Healthcare)

🇺🇸

Denver, Colorado, United States

Flourish Medical Research

🇺🇸

Boca Raton, Florida, United States

Apex Research

🇺🇸

Cross City, Florida, United States

Evolution Research Center

🇺🇸

Hialeah, Florida, United States

UF Health Jacksonville

🇺🇸

Jacksonville, Florida, United States

Quantum Clinical Trials

🇺🇸

Miami Beach, Florida, United States

Fiel Wellness Clinical Research LLC

🇺🇸

Miami, Florida, United States

BioPhase Research

🇺🇸

Miami, Florida, United States

United Clinical Research

🇺🇸

Miami, Florida, United States

Atlantis Clinical Research, LLC

🇺🇸

Miami, Florida, United States

Baptist Health Miami Cardiac and Vascular Institute

🇺🇸

Miami, Florida, United States

Farma Medical Inc.

🇺🇸

Miami, Florida, United States

New Access Research and Medical Center

🇺🇸

Miami, Florida, United States

Ascension Sacred Heart

🇺🇸

Pensacola, Florida, United States

Aiyan Diabetes Center

🇺🇸

Augusta, Georgia, United States

Peachtree Clinical Solutions - Noir Research Collective

🇺🇸

Powder Springs, Georgia, United States

Care Institute- High Desert

🇺🇸

Meridian, Idaho, United States

Northshore University Health System

🇺🇸

Evanston, Illinois, United States

Indiana Medical Research Institute

🇺🇸

Indianapolis, Indiana, United States

Franciscan Physician Network- Indiana Heart Physicians

🇺🇸

Indianapolis, Indiana, United States

MercyOne Iowa Heart Center

🇺🇸

West Des Moines, Iowa, United States

St Elizabeth Health Care - CRI

🇺🇸

Edgewood, Kentucky, United States

UofL Health

🇺🇸

Louisville, Kentucky, United States

Flourish Bowie dba Flourish Research

🇺🇸

Bowie, Maryland, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Minneapolis Heart Institute Foundation

🇺🇸

Minneapolis, Minnesota, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Boeson Research Kalispell

🇺🇸

Kalispell, Montana, United States

Boeson Research Fort Missoula

🇺🇸

Missoula, Montana, United States

Bryan Heart

🇺🇸

Lincoln, Nebraska, United States

Vector Clinical Trials

🇺🇸

Las Vegas, Nevada, United States

Advanced Heart and Vascular Institute of Hunterdon

🇺🇸

Flemington, New Jersey, United States

Virtua Health, Inc.

🇺🇸

Marlton, New Jersey, United States

Rutgers State University

🇺🇸

New Brunswick, New Jersey, United States

The Valley Hospital

🇺🇸

Paramus, New Jersey, United States

Holy Name Medical Center

🇺🇸

Teaneck, New Jersey, United States

Clindove Research

🇺🇸

Brooklyn, New York, United States

Swift Clinical Research

🇺🇸

Brooklyn, New York, United States

Northwell Health Northern Westchester Hospital

🇺🇸

Mount Kisco, New York, United States

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

West Clinical Research

🇺🇸

Morehead City, North Carolina, United States

Wake Forest University Health Sciences

🇺🇸

Winston-Salem, North Carolina, United States

Summa Health

🇺🇸

Akron, Ohio, United States

Medical Research International, LLC

🇺🇸

Oklahoma City, Oklahoma, United States

Ascension St. John - Jane Phillips Medical Center

🇺🇸

Tulsa, Oklahoma, United States

Capital Area Research

🇺🇸

Camp Hill, Pennsylvania, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

University of Tennessee Medical Center

🇺🇸

Knoxville, Tennessee, United States

TriStar Centennial Medical Center (HCA Health Care)

🇺🇸

Nashville, Tennessee, United States

Hendrick Health

🇺🇸

Abilene, Texas, United States

Gadolin Research

🇺🇸

Beaumont, Texas, United States

Helium Research Group

🇺🇸

Houston, Texas, United States

Kelsey Research Foundation

🇺🇸

Houston, Texas, United States

Gulf Coast Clinical Research, LLC

🇺🇸

Houston, Texas, United States

Aeres Clinical Research

🇺🇸

Laredo, Texas, United States

DC Clinical Research

🇺🇸

Lewisville, Texas, United States

North Dallas Research Associates - Kerlo Network

🇺🇸

McKinney, Texas, United States

SMS Clinical Research

🇺🇸

Mesquite, Texas, United States

Chippenham Johnston Willis Medical Center

🇺🇸

Richmond, Virginia, United States

Charleston Area Medical Center

🇺🇸

Charleston, West Virginia, United States

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