Diabetes Mellitus, Type 2Phase 4APPLE TREENCT06642272
A Pragmatic Trial Comparing Empagliflozin and Dapagliflozin Through Cluster Randomization Embedded in the Electronic Health Record
A Phase 4 study testing Empagliflozin 10 MG and Dapagliflozin 10 MG in people with Diabetes Mellitus, Type 2 and Heart Failure, run by Herlev and Gentofte Hospital at 12 sites in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2, Heart Failure, Chronic Kidney Diseases
- What is being tested?
- Empagliflozin 10 MG and Dapagliflozin 10 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17,200 participants
- Where
- 12 sitesDenmark
- Study dates
- 10 Oct 2024to 31 Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18 years or more
Who cannot join
- Incapabability of giving informed consent
- Withdrawal of informed consent
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Denmark12 sites, 12 recruiting
- Recruiting
Bispebjerg Hospital
Copenhagen
- Recruiting
Rigshospitalet
Copenhagen
- Recruiting
Herlev and Gentofte Hospital
Herlev
Morten Schou, Professor, 004540523920, morten.schou.04@regionh.dk
Daniel M. Christensen, MD, PhD, 004526248546, dmc@dadlnet.dk
- Recruiting
Steno Diabetes Center Copenhagen
Herlev
- Recruiting
Nordsjællands Hospital
Hillerød
- Recruiting
Holbæk Sygehus
Holbæk
- Recruiting
Hvidovre Hospital
Hvidovre
- Recruiting
Sjællands Universitetshospital
Køge
- Recruiting
Nykøbing F. Sygehus
Nykøbing Falster
- Recruiting
Bornholms Hospital
Rønne
- Recruiting
Sjællands Universitetshospital
Roskilde
- Recruiting
Slagelse Sygehus
Slagelse
About this study
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
- Being tested
- Empagliflozin 10 MG, Dapagliflozin 10 MG
- Medical subject headings
- Diabetes Mellitus, Type 2, Heart Failure, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MGDrug
Once daily
Dapagliflozin 10 MGDrug
Once daily
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin 10 MG | Other | Head-to-head comparator Receives: Drug: Empagliflozin 10 MG |
| Dapagliflozin 10 MG | Other | Head-to-head comparator Receives: Drug: Dapagliflozin 10 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 24 months
Secondary outcomes (7)
All-cause mortality
Measured: Up to 24 months
Hospitalization for heart failure
Measured: Up to 24 months
Hospitalization for myocardial infarction
Measured: Up to 24 months
Hospitalization for ischemic stroke
Measured: 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
Measured: Up to 24 months
Hospitalization for coronary revascularization
Measured: Up to 24 months
Hospitalization for unstable angina
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2024
- Study start10 Oct 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Herlev and Gentofte Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Mølager Christensen, Herlev and Gentofte Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06642272
- Sponsor's protocol ID
- 2401312
- Acronym
- APPLE TREE
- Status last verified
- Sep 2026
- First submitted
- 10 Oct 2024
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pragmatic Trial Comparing Empagliflozin and Dapagliflozin Through Cluster Randomization Embedded in the Electronic Health Record
- ClinicalTrials.gov ID
- NCT06642272
- Acronym / sponsor ID
- APPLE TREE / 2401312
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 17,200 participants (estimated)
- Lead sponsor
- Herlev and Gentofte HospitalUniversity, hospital or other
- Study start
- 10 Oct 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 15 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin 10 MG | Other | Drug: Empagliflozin 10 MGHead-to-head comparator |
| Dapagliflozin 10 MG | Other | Drug: Dapagliflozin 10 MGHead-to-head comparator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adults aged 18 years or more
Key exclusion criteria (2 listed)
- Incapabability of giving informed consent
- Withdrawal of informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 10 MGOnce daily | Drug | Empagliflozin 10 MG |
| Dapagliflozin 10 MGOnce daily | Drug | Dapagliflozin 10 MG |
Primary outcome
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.
Time frame: Up to 24 months
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
7 secondary outcomes
All-cause mortality
Time frame: Up to 24 months
Hospitalization for heart failure
Time frame: Up to 24 months
Hospitalization for myocardial infarction
Time frame: Up to 24 months
Hospitalization for ischemic stroke
Time frame: Up to 24 months
Incident or worsening nephropathy
Time frame: Up to 24 months
Hospitalization for coronary revascularization
Time frame: Up to 24 months
Hospitalization for unstable angina
Time frame: Up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empagliflozin 10 MG and Dapagliflozin 10 MG in people with Diabetes Mellitus, Type 2 and Heart Failure, run by Herlev and Gentofte Hospital at 12 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Morten Schou, Professor (004540523920, morten.schou.04@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.