PREvention of CardIovascular and DiabEtic kidNey Disease in Type 2 Diabetes (PRECIDENTD)

PRECIDENTD: PREvention of CardIovascular and DiabEtic kidNey Disease in Type 2 Diabetes

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.

Study Overview

• Status: Recruiting
• Conditions: Type2Diabetes; ASCVD
• Intervention / Treatment: Drug: SGLT2 inhibitor; Drug: GLP-1 receptor agonist; Drug: Combination drug

• Study Type: Interventional
• Enrollment (Estimated): 9000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Brendan Everett, MD, MPH; Phone Number: 617-732-8790; Email: PRECIDENTDccc@bwh.harvard.edu
• Study Contact Backup: Name: Maureen Malloy; Phone Number: 617-732-8773; Email: PRECIDENTDccc@bwh.harvard.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins School of Medicine
      • Contact: Dan Shelton; Phone Number: 443-653-3239; Email: PRECIDENTD@jhmi.edu
      • Principal Investigator: Rita Kalyani, MD
      • Sub-Investigator: Jodi Segal, MD
      • Sub-Investigator: Dan Ford, MD
  • Missouri
    • Columbia, Missouri, United States, 65211
      • Recruiting
      • University of Missouri-Columbia
      • Contact: Tea Goletiani; Phone Number: 833-970-0046; Email: MUPRECIDENTD@health.missouri.edu
      • Principal Investigator: Camilla Manrique A, MD
      • Sub-Investigator: Guido Lastra, MD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Naomi Berrie Diabetes Center at New York Presbyterian-Columbia University
      • Principal Investigator: Jacqueline Lonier, MD
      • Sub-Investigator: Robin Goland, MD
      • Contact: Jacqueline Lonier, MD; Phone Number: 212-851-5428; Email: jyl2122@cumc.columbia.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Hospital
      • Sub-Investigator: Ranee Chatterjee, MD
      • Contact: Chad Harrell; Phone Number: 919-668-9049; Email: DukePRECIDENTD@duke.edu
      • Principal Investigator: W. Schuyler Jones, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Sub-Investigator: Marc Cornier, MD
      • Contact: Elizabeth Szwast; Phone Number: 843-792-4675; Email: hinsone@musc.edu
      • Principal Investigator: Harsha Karanchi, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Lance Roller; Phone Number: 615-875-6811; Email: Lance.j.roller@vumc.org
      • Principal Investigator: Leslee Matheny, MD
      • Sub-Investigator: Russell Rothman, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin
      • Contact: Roberta Fritz-Claus; Phone Number: 414-805-0634; Email: rfritzclaus@mcw.edu
      • Principal Investigator: Jake Decker, MD
      • Sub-Investigator: Jeffrey Whittle, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium-glucose cotransporter-2 inhibitor (SGLT2i); Therapy with an SGLT2i with proven cardiovascular benefit. This means either canagliflozin, dapagliflozin, or empagliflozin	Drug: SGLT2 inhibitor; Empagliflozin, dapagliflozin, or canagliflozin
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.	Drug: GLP-1 receptor agonist; Dulaglutide, liraglutide, 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)	Drug: Combination drug; SGLT2 inhibitor and GLP-1 receptor agonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total (first and recurrent) cardiovascular, kidney, and death events	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	Through study completion on May 1, 2028, an average of 3 years of follow up for each participant

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Patient-Centered Outcomes Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2022
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 25, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Diabetic Nephropathies; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: 2022p001160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No