Heart Failure With Preserved Ejection FractionNCT07599293
Emulation of the EMPEROR-Preserved Trial Using Healthcare Claims Data
An observational study of Heart Failure With Preserved Ejection Fraction and Chronic Heart Failure, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction, Chronic Heart Failure, Type 2 Diabetes Mellitus
- What is being tested?
- Empagliflozin and Sitagliptin
- How many people
- 39,614 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2024to 19 Jun 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Individuals aged 18 years or older with heart failure and preserved ejection fraction and type 2 diabetes
Who may be able to join
- At least 18 years of age
- Heart failure with preserved ejection fraction
- Structural heart disease
- Previous HHF
- BMI < 45 kg/m2
- Type 2 diabetes mellitus
- Use of oral diuretics
Who cannot join
- Concurrent use of both study drugs on cohort entry date
- MI, CABG or other major cardiovascular surgery, GI surgery or disorder, stroke or TIA
- Implantable cardiac defibrillator
- Hypotension
- Major surgery
- GI surgery or disorder
Show all 24Show fewer
- Cancer
- Heart transplant
- Pacemaker
- Liver disease
- Atrial fibrillation
- Hypertension
- Impaired renal function
- Anemia
- History of ketoacidosis
- Pregnancy
- Cardiomyopathy
- Valvular heart disease
- Chronic pulmonary disease
- Combined comorbidity score
- Chronic alcohol and or drug abuse
- Noncompliance
- Acute decompensated HF
- Use of SGLT2i or DPP4i
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02120
About this study
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Read the detailed description
This is a non-randomized, non-interventional study that is part of the Randomized Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT-DUPLICATE) initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School.
This study is part of a series that applies the Benchmark, Expand, and Calibration (BenchExCal) approach, in which an initial trial emulation is benchmarked against a completed randomized controlled trial (RCT) to inform a subsequent database study for related clinical questions or expanded indications. In this empirical example, the related clinical question has also been evaluated in a completed randomized trial, allowing comparison of the expanded database emulation with the corresponding RCT findings.
It is intended to emulate, as closely as is possible in healthcare insurance claims data the EMPEROR-Preserved trial described below. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding.
The EMPEROR-Preserved trial is a superiority trial to evaluate the effect of empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), vs placebo on cardiovascular death and hospitalisation for heart failure among individuals with chronic heart failure with preserved ejection fraction.
The database study is designed to emulate the EMPEROR-Preserved trial. It will be a new-user active-comparator cohort study, conducted using 3 national United States claims databases, where the effect of empagliflozin vs sitagliptin was compared, a dipeptidyl peptidase-4 inhibitor (DPP4i), on all-cause mortality and hospitalisation for heart failure. While the EMPEROR-Preserved trial was conducted in participants with and without T2DM, both subgroups showed similar effect estimates in their results. Furthermore, while the trial compared empagliflozin to placebo, sitagliptin was used as an active comparator proxy for placebo to minimize confounding by indication. Sitagliptin was specifically chosen because a major randomized controlled trial on cardiovascular outcomes demonstrated that it does not affect the cardiovascular outcomes under investigation. Furthermore, clinical guidelines during the study period recommended both SGLT2 inhibitors and DPP4 inhibitors as second- or third-line options for glucose lowering, and the therapies are similarly costly, reducing concerns about channelling of patients based on socioeconomic status.
- Conditions
- Heart Failure With Preserved Ejection Fraction, Chronic Heart Failure, Type 2 Diabetes Mellitus
- Being tested
- Empagliflozin, Sitagliptin
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmpagliflozinDrug
Initiation of empagliflozin described in electronic health records is used as the exposure.
SitagliptinDrug
Initiation of sitagliptin described in electronic health records is used as the reference.
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Exposure group Receives: Drug: Empagliflozin | |
| Sitagliptin | Reference group Receives: Drug: Sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to first occurrence of hospitalization for heart failure or all-cause mortality
The primary outcome is the time from 1 day after cohort entry to the first occurrence of either component of the composite endpoint: hospitalization for heart failure or all-cause mortality, comparing empagliflozin versus sitagliptin in patients with heart failure and preserved ejection fraction.
Measured: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Secondary outcomes (3)
Time to first occurrence of cataract surgery
The outcome is the time from 1 day after cohort entry to the first occurrence of cataract surgery as a control outcome, comparing empagliflozin versus sitagliptin.
Measured: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Time to first occurrence of lumbar radiculopathy
The outcome is the time from 1 day after cohort entry to the first occurrence of lumbar radiculopathy as a control outcome, comparing empagliflozin versus sitagliptin. Patients with a recent occurrence of lumbar radiculopathy before the follow-up time window are excluded using a 30-day lookback period.
Measured: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Time to first occurrence of hernia
The outcome is the time from 1 day after cohort entry to the first occurrence of hernia as a control outcome, comparing empagliflozin versus sitagliptin. Patients with a recent occurrence of hernia before the follow-up time window are excluded using a 30-day lookback period.
Measured: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2026
- Study start13 Oct 2024
- Primary completion19 Jun 2026
- Study completion19 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 39,614 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Responsible party
- Principal investigator, Shirley Vichy Wang, Brigham and Women's Hospital
- Investigators
- Shirley Wang, PhD, ScM, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07599293
- Sponsor's protocol ID
- 2018P002966-EMPERORPreserved
- Status last verified
- Jul 2026
- First submitted
- 14 May 2026
- Last updated
- 9 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Emulation of the EMPEROR-Preserved Trial Using Healthcare Claims Data
- ClinicalTrials.gov ID
- NCT07599293
- Acronym / sponsor ID
- 2018P002966-EMPERORPreserved
- Conditions
- Heart Failure With Preserved Ejection Fraction, Chronic Heart Failure, Type 2 Diabetes Mellitus
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 39,614 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Food and Drug Administration (FDA)
- Study start
- 13 Oct 2024 (actual)
- Primary completion
- 19 Jun 2026 (actual)
- Study completion
- 19 Jun 2026 (actual)
- First posted
- 20 May 2026 (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.
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
Detailed description
This is a non-randomized, non-interventional study that is part of the Randomized Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT-DUPLICATE) initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School.
This study is part of a series that applies the Benchmark, Expand, and Calibration (BenchExCal) approach, in which an initial trial emulation is benchmarked against a completed randomized controlled trial (RCT) to inform a subsequent database study for related clinical questions or expanded indications. In this empirical example, the related clinical question has also been evaluated in a completed randomized trial, allowing comparison of the expanded database emulation with the corresponding RCT findings.
It is intended to emulate, as closely as is possible in healthcare insurance claims data the EMPEROR-Preserved trial described below. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding.
The EMPEROR-Preserved trial is a superiority trial to evaluate the effect of empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), vs placebo on cardiovascular death and hospitalisation for heart failure among individuals with chronic heart failure with preserved ejection fraction.
The database study is designed to emulate the EMPEROR-Preserved trial. It will be a new-user active-comparator cohort study, conducted using 3 national United States claims databases, where the effect of empagliflozin vs sitagliptin was compared, a dipeptidyl peptidase-4 inhibitor (DPP4i), on all-cause mortality and hospitalisation for heart failure. While the EMPEROR-Preserved trial was conducted in participants with and without T2DM, both subgroups showed similar effect estimates in their results. Furthermore, while the trial compared empagliflozin to placebo, sitagliptin was used as an active comparator proxy for placebo to minimize confounding by indication. Sitagliptin was specifically chosen because a major randomized controlled trial on cardiovascular outcomes demonstrated that it does not affect the cardiovascular outcomes under investigation. Furthermore, clinical guidelines during the study period recommended both SGLT2 inhibitors and DPP4 inhibitors as second- or third-line options for glucose lowering, and the therapies are similarly costly, reducing concerns about channelling of patients based on socioeconomic status.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin | – | Drug: EmpagliflozinExposure group |
| Sitagliptin | – | Drug: SitagliptinReference group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals aged 18 years or older with heart failure and preserved ejection fraction and type 2 diabetes
Key inclusion criteria (7 listed)
- At least 18 years of age
- Heart failure with preserved ejection fraction
- Structural heart disease
- Previous HHF
- BMI < 45 kg/m2
Key exclusion criteria (24 listed)
- Concurrent use of both study drugs on cohort entry date
- MI, CABG or other major cardiovascular surgery, GI surgery or disorder, stroke or TIA
- Implantable cardiac defibrillator
- Hypotension
- Major surgery
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 |
|---|---|---|
| EmpagliflozinInitiation of empagliflozin described in electronic health records is used as the exposure. | Drug | Empagliflozin |
| SitagliptinInitiation of sitagliptin described in electronic health records is used as the reference. | Drug | Sitagliptin |
Primary outcome
Time to first occurrence of hospitalization for heart failure or all-cause mortality
Time frame: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
The primary outcome is the time from 1 day after cohort entry to the first occurrence of either component of the composite endpoint: hospitalization for heart failure or all-cause mortality, comparing empagliflozin versus sitagliptin in patients with heart failure and preserved ejection fraction.
3 secondary outcomes
Time to first occurrence of cataract surgery
Time frame: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Time to first occurrence of lumbar radiculopathy
Time frame: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Time to first occurrence of hernia
Time frame: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 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. This study is not recruiting at the moment.
Shirley Wang, PhD, ScM principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure With Preserved Ejection Fraction and Chronic Heart Failure, run by Brigham and Women's Hospital at 1 site in United States.
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 7 inclusion and 24 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: finished, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to first occurrence of hospitalization for heart failure or all-cause mortality (time frame: From 1 day after entry through first occurrence of outcome, disenrollment, end of study period, treatment discontinuation +45-day grace/risk window, treatment switch, nursing home admission, or start of other SGLT2i or DPP4i, assessed up to 1 year.). 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 9 Jul 2026.