## Protocol Section
### Identification Module
**NCT ID:** NCT06424288

**Brief Title:** A Study to Test Whether BI 690517 in Combination With Empagliflozin Helps People With Heart Failure

**Official Title:** A Phase III Double-blind, Randomised, Parallel-group Superiority Trial to Evaluate Efficacy and Safety of the Combined Used of Oral BI 690517 and Empagliflozin Compared With Placebo and Empagliflozin in Patients With Heart Failure (HF) (New York Heart Association [NYHA] Classes II to IV) and Left Ventricular Ejection Fraction (LVEF) ≥40%

#### Organization Study ID Info
**ID:** 1378-0020
#### Organization
**Class:** INDUSTRY
**Full Name:** Boehringer Ingelheim
#### Secondary ID Infos
**Domain:** CTIS
**ID:** 2023-509706-30-00
**Type:** REGISTRY
**Domain:** WHO International Clinical Trials Registry Platform (ICTRP)
**ID:** U1111-1302-4422
**Type:** REGISTRY
### Status Module
#### Completion Date
**Date:** 2027-11-15

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-11-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-27

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-10
**Study First Submit QC Date:** 2024-05-21
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Boehringer Ingelheim

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This study is open to adults aged 18 or above legal age with heart failure. People can join the study if they have heart failure symptoms and a left ventricular ejection fraction (LVEF) of 40% or more. The purpose of this study is to find out whether BI 690517 in combination with empagliflozin helps people with heart failure.

Participants are put into 2 groups by chance. Every participant has an equal chance of being in each group. The groups are:

* BI 690517 and empagliflozin group: participants take BI 690517 and empagliflozin as tablets once a day.
* Placebo and empagliflozin group: participants take placebo and empagliflozin as tablets once a day.

Participants can stay in the study as long as they benefit from treatment and can tolerate it. During this time, they visit their doctors regularly. The doctors regularly check participants' health and take note of any unwanted effects. The study staff may also contact the participants by phone. Participants also regularly answer questions about their well-being.

The study does not have a fixed duration. It continues until we have enough data to see if the treatment is working.

### Conditions Module

**Conditions:**

- Heart Failure

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 6000

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: BI 690517

- Drug: Empagliflozin

**Label:** BI 690517 + empagliflozin

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: Empagliflozin

- Drug: Placebo

**Label:** Placebo + empagliflozin

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- BI 690517 + empagliflozin

**Description:** BI 690517

**Name:** BI 690517

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- BI 690517 + empagliflozin

- Placebo + empagliflozin

**Description:** Empagliflozin

**Name:** Empagliflozin

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Placebo + empagliflozin

**Description:** Placebo matching BI 690517

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Time to first event of Cardiovascular (CV) death or Hospitalisation for heart failure (HHF)

**Time Frame:** up to 42 months

#### Secondary Outcomes

**Measure:** Key secondary endpoint: Time to first event of CV death, HHF or urgent heart failure visit

**Time Frame:** up to 42 months

**Measure:** Key secondary endpoint: Occurrence of HHFs (first and recurrent)

**Time Frame:** up to 42 months

**Description:** The Kansas City Cardiomyopathy Questionnaire is a patient-reported outcome instrument for use in clinical investigations in heart failure.

The Total Symptom Score measures the following aspects of symptom experience in two domain scores:

The "Symptom Frequency Domain" assesses frequency of the following experiences:

* Lower extremity swelling in the morning
* Fatigue limiting patients' ability to do what they want
* Dyspnea limiting patients' ability to do what they want
* Dyspnea forcing patients to sleep upright/elevated

The "Symptom Burden Domain" assesses bothersomeness of the following symptoms:

* Fatigue
* Dyspnea
* Lower extremity swelling All KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent.

**Measure:** Key secondary endpoint: Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) at Week 32

**Time Frame:** at baseline, at week 32

**Measure:** Key secondary endpoint: Time to CV death

**Time Frame:** up to 42 months

**Measure:** Key secondary endpoint: Time to all-cause mortality

**Time Frame:** up to 42 months

**Measure:** Time to first HHF

**Time Frame:** up to 42 months

**Description:** \* chronic dialysis is defined as dialysis continuing for at least 30 days

\*\* using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation ((CKD-EPI)cr)

**Measure:** Time to first occurrence of death from kidney failure, chronic dialysis* or renal transplant or sustained reduction of ≥40% estimated glomerular filtration rate (eGFR)** or sustained eGFR (CKD-EPI)cr <10 mL/min/1.73 m² (composite renal endpoint)

**Time Frame:** up to 42 months

**Description:** The KCCQ Clinical Summary Score is a composite of the Total Symptom Score and Physical Limitations Score.

The "Physical Limitations Score" measures the following physical limitations:

* Dressing
* Showering/bathing
* Walking one block on level ground
* Doing yardwork, housework or carrying groceries
* Climbing a flight of stairs without stopping
* Hurrying or jogging as if to catch a bus All KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent.

**Measure:** Absolute change from baseline in KCCQ Clinical Summary Score (KCCQ-CSS) at Week 32

**Time Frame:** at baseline, at week 32

**Measure:** Absolute change from baseline in KCCQ-TSS at Week 52

**Time Frame:** at baseline, at week 52

### Eligibility Module

**Eligibility Criteria:** Inclusion criteria:

1. At least 18 years old and at least of the legal age of consent in countries where it is greater than 18 years
2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
3. Male or female participants. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria and instructions on the duration of their use is provided in the participant information
4. Chronic Heart failure (HF) diagnosed at least 3 months before Visit 1, and in New York Heart Association (NYHA) class II-IV at Visit 1, with left ventricular ejection fraction (LVEF) ≥40% per local reading. A historical LVEF may be used if it was measured within 12 months prior to Visit 1, or the LVEF may be measured after study consent has been obtained and before Visit 2
5. Presence of structural heart abnormality (confirmed by any imaging modality; i.e. echocardiography at Visit 1, as defined by left ventricular hypertrophy or left atrial enlargement). Historical imaging may be used if performed within 12 months prior to Visit 1, or imaging may be completed after study consent has been obtained and before Visit 2
6. Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) at Visit 1, analysed at the central laboratory at Visit 1:

   1. in participants with body mass index (BMI) \<27 kg/m²: ≥300 pg/mL for participants without atrial fibrillation (Afib) or atrial flutter (Aflutter) (at Visit 1 electrocardiogram (ECG)) and ≥900 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)
   2. in participants with BMI ≥27 kg/m² to \<35 kg/m²: ≥220 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and ≥660 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)
   3. in participants with BMI ≥35 kg/m²: ≥125 pg/mL for participants without Afib or Aflutter (at Visit 1 ECG) and ≥375 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)
7. At least one of the following:

   * Currently treated with diuretic therapy e.g. loop diuretics or thiazides, and on a stable dose for at least 1 week prior to Visit 1
   * Documented hospitalisation for HF within 6 months prior to Visit 1
   * Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1

     * in participants without Afib or Aflutter (at Visit 1 ECG): ≥900 pg/mL
     * for participants with Afib or Aflutter (at Visit 1 ECG): ≥1800 pg/mL
8. Participants must be treated according to best possible standard of care (SOC) in accordance with applicable HF local/international guidelines (according to the judgment of the investigator)

Exclusion criteria:

1. Treatment with an mineralocorticoid receptor antagonist (MRA) (e.g. spironolactone, eplerenone, finerenone) within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator. Treatment with MRA should not be interrupted with the intention of enrolment into the study
2. Treatment with amiloride, or other potassium-sparing diuretic within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator
3. Receiving the following treatments:

   * a direct renin inhibitor (e.g. aliskiren) at Visit 2
   * more than one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI), or two simultaneously at Visit 2
   * Acute decompensated HF requiring hospitalisation or i.v. therapy including diuretics, or i.v. inotropes or i.v. vasodilators, mechanical support (such as an intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device), or IV natriuretic peptide (e.g. nesiritide) within the past 7 days prior to Visit 2
4. Myocardial infarction (MI), cerebrovascular accident (CVA), transient ischemic attack (TIA), stroke, coronary artery bypass graft (CABG) surgery, heart valve surgery or any other major surgery (major according to the investigator's assessment) within 90 days prior to Visit 1, or scheduled for major elective surgery (e.g. hip replacement, coronary artery bypass graft surgery/CABG)
5. Heart transplant recipient, awaiting heart transplant, or currently implanted left ventricular assist device (LVAD)
6. Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within the 12 months prior to Visit 1 and until Visit 2
7. Acute inflammatory heart disease, such as acute myocarditis, within the 90 days preceding prior to Visit 1 and until Visit 2
8. Known severe valvular heart disease (obstructive or regurgitant), as per investigator's judgment, or valvular heart disease scheduled for surgical or invasive procedures at Visit 1, or anticipated invasive treatment during the study Further exclusion criteria apply.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** lintriage.rdg@boehringer-ingelheim.com

**Name:** Boehringer Ingelheim

**Phone:** 1-800-243-0127

**Role:** CONTACT

### IPD Sharing Statement Module

**Access Criteria:** For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

**Description:** Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- CSR

**IPD Sharing:** YES

**Time Frame:** One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.

**URL:** https://www.mystudywindow.com/msw/datasharing

### References Module

#### See Also Links

**Label:** Related Info

**URL:** https://www.mystudywindow.com

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M9421

- Name: Heart Failure

- Relevance: HIGH

- As Found: Heart Failure

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006333

- Term: Heart Failure

### Intervention Browse Module - Ancestors

- ID: D000077203

- Term: Sodium-Glucose Transporter 2 Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M258082

- Name: Empagliflozin

- Relevance: HIGH

- As Found: Part 1

- ID: M1691

- Name: Sodium-Glucose Transporter 2 Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000570240

- Term: Empagliflozin

### Misc Info Module

- Version Holder: 2024-05-31
