A Pragmatic Trial Comparing Empagliflozin and Dapagliflozin Through Cluster Randomization Embedded in the Electronic Health Record (APPLE TREE)

The aim of this clinical trial is investigate the comparative effectiveness of empagliflozin and dapagliflozin for the treatment of diabetes, chronic kidney disease, and heart failure.

Patients who are prescribed either empagliflozin or dapagliflozin, as part of daily clinical practice at the participating sites, will be included in the study. Treatment will be randomized automatically through the electronic health record software in clusters defined by time of day.

https://www.appletreestudy.com

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Diabetes Mellitus, Type 2; Chronic Kidney Diseases
• Intervention / Treatment: Drug: Empagliflozin 10 MG; Drug: Dapagliflozin 10 MG

• Study Type: Interventional
• Enrollment (Estimated): 17200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Morten Schou, Professor; Phone Number: 004540523920; Email: morten.schou.04@regionh.dk
• Study Contact Backup: Name: Daniel M. Christensen, MD, PhD; Phone Number: 004526248546; Email: dmc@dadlnet.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet
  • Copenhagen, Denmark
    • Recruiting
    • Bispebjerg Hospital
  • Herlev, Denmark
    • Recruiting
    • Herlev and Gentofte Hospital
    • Contact: Morten Schou, Professor; Phone Number: 004540523920; Email: morten.schou.04@regionh.dk
    • Contact: Daniel M. Christensen, MD, PhD; Phone Number: 004526248546; Email: dmc@dadlnet.dk
    • Principal Investigator: Morten Schou
  • Herlev, Denmark
    • Recruiting
    • Steno Diabetes Center Copenhagen
  • Hillerød, Denmark
    • Recruiting
    • Nordsjællands Hospital
  • Holbæk, Denmark
    • Recruiting
    • Holbæk Sygehus
  • Hvidovre, Denmark
    • Recruiting
    • Hvidovre Hospital
  • Køge, Denmark
    • Recruiting
    • Sjællands Universitetshospital
  • Nykøbing Falster, Denmark
    • Recruiting
    • Nykøbing F. Sygehus
  • Roskilde, Denmark
    • Recruiting
    • Sjællands Universitetshospital
  • Rønne, Denmark
    • Recruiting
    • Bornholms Hospital
  • Slagelse, Denmark
    • Recruiting
    • Slagelse Sygehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 years or more

Exclusion Criteria:

• Incapabability of giving informed consent
• Withdrawal of informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Empagliflozin 10 MG; Head-to-head comparator	Drug: Empagliflozin 10 MG; Once daily
Other: Dapagliflozin 10 MG; Head-to-head comparator	Drug: Dapagliflozin 10 MG; Once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the first occurrence of any of the components of the composite: all-cause mortality, hospitalization for heart failure, hospitalization for myocardial infarction, hospitalization for ischemic stroke, and incident or worsening nephropathy.	Incident or worsening nephropathy is defined as: A sustained decrease in estimated glomerular filtration rate (eGFR) of ≥40% from baseline; A sustained decrease in eGFR of ≤10 per minute per 1.73 m2; Initiation of dialysis; Kidney transplantation	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality		Up to 24 months
Hospitalization for heart failure		Up to 24 months
Hospitalization for myocardial infarction		Up to 24 months
Hospitalization for ischemic stroke		Up to 24 months
Incident or worsening nephropathy	Defined as a sustained decrease in estimated glomerular filtration rate (eGFR) of ≥40% from baseline, a sustained decrease in eGFR of ≤10 per minute per 1.73 m2, initiation of dialysis, or kidney transplantation	Up to 24 months
Hospitalization for coronary revascularization		Up to 24 months
Hospitalization for unstable angina		Up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization for ketoacidosis	Safety outcome	Up to 24 months
Hospitalization for limb amputation	Safety outcome	Up to 24 months
Hospitalization for genitourinary infection	Safety outcome	Up to 24 months
Hospitalization for fracture	Safety outcome	Up to 24 months

Collaborators and Investigators

• Sponsor: Herlev and Gentofte Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: October 10, 2024
• First Submitted That Met QC Criteria: October 12, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 1, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Renal Insufficiency; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Empagliflozin; Dapagliflozin
• Other Study ID Numbers: 2401312

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No