Clinical trial NCT06112418: A Randomized Comparison of Stage-Based Care Versus Risk Factor-Based Care for Prevention of Cardiovascular Events
Official title: A Randomized Comparison of Cleerly Coronary Artery Disease Stage-Based Care Versus Risk Factor-Based Care for Primary Prevention of Cardiovascular Events
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 2
PreDiabetes
Metabolic Syndrome
Lead sponsor: Cleerly, Inc.
Sponsor class: INDUSTRY
Collaborators: name: CPC Clinical Research
First posted: 2023-11-01
Enrollment: 7500
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, open blinded endpoint (PROBE), event-driven pragmatic trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: The primary objective is to compare Cleerly stage-based care with risk factor-based care on the risk of CV events.
timeFrame: Through study completion- an average of 3.5 years
Secondary outcomes:
measure: 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.
timeFrame: Through study completion- an average of 3.5 years
measure: 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.
timeFrame: Through study completion- an average of 3.5 years
measure: 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.
timeFrame: Through study completion- an average of 3.5 years
measure: 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.
timeFrame: Through study completion- an average of 3.5 years
measure: 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.
timeFrame: Through study completion- an average of 3.5 years
Other outcomes:
measure: The safety objective is to assess harm with the 2 prevention strategies
timeFrame: Through study completion- an average of 3.5 years
measure: The safety objective is to assess harm with the 2 prevention strategies
timeFrame: Through study completion- an average of 3.5 years
Locations:
city: Chandler
country: United States
facility: Chandler Clinical Trials
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Clinical Trials
state: Arizona
city: Sun City
country: United States
facility: Sun City Research
state: Arizona
city: Tucson
country: United States
facility: Noble Clinical Research
state: Arizona
city: Beverly Hills
country: United States
facility: Cardiovascular Research Foundation of Southern California
state: California
city: Beverly Hills
country: United States
facility: Amicis Research: Beverly Hills
state: California
city: Canoga Park
country: United States
facility: Valiance Clinical Research - Canoga Park
state: California
city: Chula Vista
country: United States
facility: Cardiovascular Institute of San Diego
state: California
city: Granada Hills
country: United States
facility: Amicis Research: Granada Hills
state: California
city: Huntington Park
country: United States
facility: Valiance Clinical Research: Huntington Park
state: California
city: Long Beach
country: United States
facility: Long Beach Research Institute
state: California
city: Newhall
country: United States
facility: Amicis Research: Newhall
state: California
city: Northridge
country: United States
facility: Ace Research Institute: Northridge
state: California
city: Northridge
country: United States
facility: Amicis Research: Northridge
state: California
city: Northridge
country: United States
facility: Ace Research Institute: Northridge #2
state: California
city: Northridge
country: United States
facility: Northridge Clinical Trials
state: California
city: San Fernando
country: United States
facility: Amicis Research: San Fernando
state: California
city: Tarzana
country: United States
facility: Valiance Clinical Research - Tarzana
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor - UCLA Medical Center
state: California
city: Valencia
country: United States
facility: Amicis Research: Valencia
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Denver
country: United States
facility: St. Josephs (Intermountain Healthcare)
state: Colorado
city: Boca Raton
country: United States
facility: Flourish Medical Research
state: Florida
city: Cross City
country: United States
facility: Apex Research
state: Florida
city: Hialeah
country: United States
facility: Evolution Research Center
state: Florida
city: Jacksonville
country: United States
facility: UF Health Jacksonville
state: Florida
city: Miami Beach
country: United States
facility: Quantum Clinical Trials
state: Florida
city: Miami
country: United States
facility: Fiel Wellness Clinical Research LLC
state: Florida
city: Miami
country: United States
facility: BioPhase Research
state: Florida
city: Miami
country: United States
facility: United Clinical Research
state: Florida
city: Miami
country: United States
facility: Atlantis Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Baptist Health Miami Cardiac and Vascular Institute
state: Florida
city: Miami
country: United States
facility: Farma Medical Inc.
state: Florida
city: Miami
country: United States
facility: New Access Research and Medical Center
state: Florida
city: Pensacola
country: United States
facility: Ascension Sacred Heart
state: Florida
city: Augusta
country: United States
facility: Aiyan Diabetes Center
state: Georgia
city: Powder Springs
country: United States
facility: Peachtree Clinical Solutions - Noir Research Collective
state: Georgia
city: Meridian
country: United States
facility: Care Institute- High Desert
state: Idaho
city: Evanston
country: United States
facility: Northshore University Health System
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Medical Research Institute
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan Physician Network- Indiana Heart Physicians
state: Indiana
city: West Des Moines
country: United States
facility: MercyOne Iowa Heart Center
state: Iowa
city: Edgewood
country: United States
facility: St Elizabeth Health Care - CRI
state: Kentucky
city: Louisville
country: United States
facility: UofL Health
state: Kentucky
city: Bowie
country: United States
facility: Flourish Bowie dba Flourish Research
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Kalispell
country: United States
facility: Boeson Research Kalispell
state: Montana
city: Missoula
country: United States
facility: Boeson Research Fort Missoula
state: Montana
city: Lincoln
country: United States
facility: Bryan Heart
state: Nebraska
city: Las Vegas
country: United States
facility: Southwest Medical Associates- Optum Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Vector Clinical Trials
state: Nevada
city: Flemington
country: United States
facility: Advanced Heart and Vascular Institute of Hunterdon
state: New Jersey
city: Marlton
country: United States
facility: Virtua Health, Inc.
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers State University
state: New Jersey
city: Paramus
country: United States
facility: The Valley Hospital
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: Clindove Research
state: New York
city: Brooklyn
country: United States
facility: Swift Clinical Research
state: New York
city: Mount Kisco
country: United States
facility: Northwell Health Northern Westchester Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Morehead City
country: United States
facility: West Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Summa Health
state: Ohio
city: Oklahoma City
country: United States
facility: Medical Research International, LLC
state: Oklahoma
city: Tulsa
country: United States
facility: Ascension St. John - Jane Phillips Medical Center
state: Oklahoma
city: Camp Hill
country: United States
facility: Capital Area Research
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: TriStar Centennial Medical Center (HCA Health Care)
state: Tennessee
city: Abilene
country: United States
facility: Hendrick Health
state: Texas
city: Beaumont
country: United States
facility: Gadolin Research
state: Texas
city: Houston
country: United States
facility: Helium Research Group
state: Texas
city: Houston
country: United States
facility: Kelsey Research Foundation
state: Texas
city: Houston
country: United States
facility: Gulf Coast Clinical Research, LLC
state: Texas
city: Laredo
country: United States
facility: Aeres Clinical Research
state: Texas
city: Lewisville
country: United States
facility: DC Clinical Research
state: Texas
city: McKinney
country: United States
facility: North Dallas Research Associates - Kerlo Network
state: Texas
city: Mesquite
country: United States
facility: SMS Clinical Research
state: Texas
city: Richmond
country: United States
facility: Chippenham Johnston Willis Medical Center
state: Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
Study officials:
affiliation: Mt. Sinai Heart
name: Deepak Bhatt, MD, MPH
role: STUDY_CHAIR
References:
citation: Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y, Elkind MSV, Evenson KR, Eze-Nliam C, Ferguson JF, Generoso G, Ho JE, Kalani R, Khan SS, Kissela BM, Knutson KL, Levine DA, Lewis TT, Liu J, Loop MS, Ma J, Mussolino ME, Navaneethan SD, Perak AM, Poudel R, Rezk-Hanna M, Roth GA, Schroeder EB, Shah SH, Thacker EL, VanWagner LB, Virani SS, Voecks JH, Wang NY, Yaffe K, Martin SS. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation. 2022 Feb 22;145(8):e153-e639. doi: 10.1161/CIR.0000000000001052. Epub 2022 Jan 26.
citation: Clerc OF, Fuchs TA, Stehli J, Benz DC, Grani C, Messerli M, Giannopoulos AA, Buechel RR, Luscher TF, Pazhenkottil AP, Kaufmann PA, Gaemperli O. Non-invasive screening for coronary artery disease in asymptomatic diabetic patients: a systematic review and meta-analysis of randomised controlled trials. Eur Heart J Cardiovasc Imaging. 2018 Aug 1;19(8):838-846. doi: 10.1093/ehjci/jey014.