PREvention of CardIovascular and DiabEtic kidNey Disease in Type 2 Diabetes
Purpose
PRECIDENTD is a randomized, open label, pragmatic clinical trial designed to compare rates of the total number of cardiovascular, kidney, and death events among two alternative treatments for patients with type 2 diabetes (T2D) and either established atherosclerotic cardiovascular disease (ASCVD) or at high risk for ASCVD. To accomplish this objective, we will randomly assign 6,000 patients with established T2D and ASCVD or high-risk for ASCVD in a 1:1 allocation to sodium-glucose cotransporter-2 inhibitor (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP-1RA). Participants will be followed for the occurrence of the trial primary endpoint of the total (first and recurrent) number of episodes of myocardial infarction (MI), stroke, arterial revascularization, hospitalization for heart failure, development of end-stage kidney disease, kidney transplantation, and mortality, counting all events from randomization until end of study.
Conditions
- Type2Diabetes
- ASCVD
Eligibility
- Eligible Ages
- Between 40 Years and 80 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Type 2 diabetes based on clinical diagnosis - HbA1c ≥6% measured within 12 months prior to screening - Secondary prevention cohort (at least 70% of cohort): - Age 40 to 80 years - Evidence of established atherosclerotic cardiovascular disease (ASCVD), as defined by one or more of the following - Coronary heart disease defined by at least one of the following: prior myocardial infarction, prior coronary percutaneous coronary intervention, ≥50% stenosis of a coronary artery documented by invasive or non-invasive imaging (including CT coronary angiography), positive stress test, or coronary artery calcium score >400 Agatston units; - Cerebrovascular disease defined by at least one of the following: prior ischemic stroke, prior carotid revascularization procedure, carotid stenosis ≥ 50% documented by X-ray angiography, MR angiography, CT angiography, or Doppler ultrasound; - Symptomatic peripheral artery disease defined by at least one of the following: leg symptoms with an ABI ≤ 0.9, leg symptoms with imaging evidence of a stenosis ≥50% in a peripheral artery documented by X-ray angiography, MR angiography, CT angiography, or Doppler ultrasound, or prior amputation for atherosclerotic disease. - Primary prevention cohort (capped at 30% of cohort): - Age 60-80 years and at least 1 additional high-risk feature: - Cardiovascular risk factors/high-risk features: - Active smoking (combustible tobacco or marijuana) - HbA1c ≥ 8% measured within 12 months prior to screening. The most recent value available at the time of screening will be used for screening and to determine eligibility. - Stage 3a CKD, eGFR 45-59 ml/min/1.73m2 measured within 12 months prior to screening. The most recent value available at screening will be used for screening and to determine eligibility. - Willingness to be randomly assigned to medication class (SGLT2i or GLP-1 RA or both) and fill prescription through personal pharmacy benefit while having other medications adjusted for safety - Willingness to avoid starting a therapy in the alternative treatment group (e.g., if randomized to GLP-1 RA, avoid starting an SGLT2i) unless strongly recommended by the participant's usual care provider. - If taking one of the study medication classes, willingness to stop SGLT2i or GLP-1 RA and be randomly assigned to one of the two medication classes - Willingness to consent to data collection using the electronic health record and sign a medical release to obtain future medical records from other health care facilities
Exclusion Criteria
- Known or suspected diabetes of other cause (type 1 diabetes, pancreatogenic diabetes, monogenic diabetes, etc.) - Any background diabetes medication regimen will be allowed in this pragmatic trial with the following proviso: o Participants taking basal-bolus, prandial, or multiple daily injection insulin (MDI) regimens (e.g., short-acting in combination with long-acting insulin, called MDI regimens) are eligible only if the research staff attests that there has been communication with the usual diabetes care provider and that the provider has agreed to manage insulin adjustment with initiation of study medications. If such agreement has not been obtained, participants taking MDI regimens are excluded. - History of diabetic ketoacidosis - Active diabetic foot ulcer - History of pancreatitis - Heart failure as a primary reason for hospitalization within the past year - Known left ventricular ejection fraction <40% - Known urinary albumin-to-creatinine ratio >200 mg/g at screening - Estimated glomerular filtration rate (eGFR) less than 45 ml/min/1.73m2 measured within 12 months prior to screening. The most recent value available at screening will be used for screening and to determine eligibility. - Known inability to afford study medication through current insurance coverage. - If a woman of child-bearing potential, the patient or partner is unwilling to use birth control - Active treatment for cancer, planned treatment for cancer, or recent active cancer with likelihood of recurrence or progression, which, in the opinion of the site investigator, has a likelihood of recurrence that would interfere with study therapy prior to 2028 - Treated cancer with no evidence of disease, no evidence of disease progression, and no planned change in therapy is allowed. Examples of allowable cancers include: - Breast cancer stable after active treatment, managed with long-term anti-estrogen therapy - Prostate cancer being observed - Stage 0 or 1 tumors status post resection or other definitive treatment - Other similarly stable cancer comorbidities - History of solid organ or bone marrow transplant - Allergy to SGLT2 inhibitor or GLP-1 receptor agonist
Study Design
- Phase
- Phase 4
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Prevention
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Sodium-glucose cotransporter-2 inhibitor (SGLT2i) |
Therapy with an SGLT2i with proven cardiovascular benefit. This means either canagliflozin, dapagliflozin, or empagliflozin |
|
|
Active Comparator Glucagon-like peptide-1 receptor agonist (GLP-1 RA) |
Therapy with a GLP-1 RA with proven cardiovascular benefit. This means either dulaglutide, liraglutide, or semaglutide. |
|
Recruiting Locations
Longwood Research LLC
Huntsville, Alabama 35801
Huntsville, Alabama 35801
HonorHealth Research & Innovation Institute
Scottsdale, Arizona 85258
Scottsdale, Arizona 85258
Eastside Clinical Research Associates
Los Angeles, California 90022
Los Angeles, California 90022
Kendall South Medical Center, Inc
Miami, Florida 33185
Miami, Florida 33185
South Florida Research Solutions, LLC
Pembroke Pines, Florida 33028
Pembroke Pines, Florida 33028
NSC Research, Inc.
Johns Creek, Georgia 30024
Johns Creek, Georgia 30024
Herman Clinical Research
Suwanee, Georgia 30024
Suwanee, Georgia 30024
University of Illinois Chicago
Chicago, Illinois 60612
Chicago, Illinois 60612
Rush University Medical Center
Hinsdale, Illinois 60521
Hinsdale, Illinois 60521
University of Iowa
Iowa City, Iowa 52242
Iowa City, Iowa 52242
University of Kansas Medical Center
Fairway, Kansas 66205
Fairway, Kansas 66205
Johns Hopkins School of Medicine
Baltimore, Maryland 21205
Baltimore, Maryland 21205
MedStar Union Memorial Hospital
Baltimore, Maryland 21218
Baltimore, Maryland 21218
MedStar Health Research Institute - Good Samaritan Hospital
Baltimore, Maryland 21239
Baltimore, Maryland 21239
Brigham and Women's Hospital
Boston, Massachusetts 02115
Boston, Massachusetts 02115
UMass Chan Medical School
Worcester, Massachusetts 01655
Worcester, Massachusetts 01655
University of Michigan
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
Essentia Health
Duluth, Minnesota 55805
Duluth, Minnesota 55805
University of Minnesota
Minneapolis, Minnesota 55455
Minneapolis, Minnesota 55455
University of Missouri-Columbia
Columbia, Missouri 65212
Columbia, Missouri 65212
University of Nebraska Medical Center
Omaha, Nebraska 68198
Omaha, Nebraska 68198
Naomi Berrie Diabetes Center at New York Presbyterian-Columbia University
New York, New York 10032
New York, New York 10032
Atrium Health Family Medicine Research Department
Charlotte, North Carolina 28207
Charlotte, North Carolina 28207
Duke University Hospital
Durham, North Carolina 27710
Durham, North Carolina 27710
Wooster Heart Group
Wooster, Ohio 44691
Wooster, Ohio 44691
Oregon Health & Science University
Portland, Oregon 97239
Portland, Oregon 97239
Geisinger Medical Center
Danville, Pennsylvania 17821
Danville, Pennsylvania 17821
Temple University Lewis Katz School of Medicine
Philadelphia, Pennsylvania 19140
Philadelphia, Pennsylvania 19140
Family Care Center at Kent Hospital
Pawtucket, Rhode Island 02860
Pawtucket, Rhode Island 02860
Medical University of South Carolina
Charleston, South Carolina 29425
Charleston, South Carolina 29425
South Carolina Clinical Research, LLC
Orangeburg, South Carolina 29118
Orangeburg, South Carolina 29118
Vanderbilt University Medical Center
Nashville, Tennessee 37232
Nashville, Tennessee 37232
Premier Internal Medicine Associates of Houston
Katy, Texas 77493
Katy, Texas 77493
North Dallas Research Associates
McKinney, Texas 75069
McKinney, Texas 75069
Kidney and Hypertension Specialists, PLLC
Manassas, Virginia 20110
Manassas, Virginia 20110
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
More Details
- NCT ID
- NCT05390892
- Status
- Recruiting
- Sponsor
- Brigham and Women's Hospital