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 three 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 9,000 patients with established T2D and ASCVD or high-risk for ASCVD in a 1:1:1 allocation to SGLT2i, GLP-1RA, or the combination. 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 Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Type 2 diabetes based on clinical diagnosis - HbA1c ≥6.5% if on no medication or >6% if on glucose-lowering medication, measured within 6 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: History of myocardial infarction or ischemic stroke or established coronary heart disease, or established peripheral artery disease, or established carotid artery atherosclerosis, or history of an arterial revascularization procedure of the coronary, peripheral, or cerebrovascular circulation - 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), or HbA1c ≥ 8%, or Stage 3a CKD (eGFR 45-59 ml/min/1.73m2). - 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 or to combination therapy - 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.) - Use of prandial or short-acting insulin in combination with basal insulin - History of diabetic ketoacidosis - Active diabetic foot ulcer - History of pancreatitis - Heart failure as a primary reason for hospitalization within the past year OR known left ventricular ejection fraction <40% - Estimated glomerular filtration rate (eGFR) less than 45 ml/min/1.73m2 - Known inability to afford study medication through current insurance coverage. - If a woman of child-bearing potential, patient, or partner unwilling to use birth control
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. |
|
|
Active Comparator Combination SGLT2i and GLP-1 RA |
Combination therapy with an SLGT2i (canagliflozin, dapagliflozin, or empagliflozin) AND a GLP-1 RA (dulaglutide, liraglutide, or semaglutide) |
|
Recruiting Locations
Vanderbilt University Medical Center
Nashville, Tennessee 37232
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Brigham and Women's Hospital