EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure EMPEROR-Preserved

• Register: EUCTR
• Last refreshed on: 25 May 2021
• Main ID: EUCTR2016-002278-11-HU
• Date of registration: 23/01/2017
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim International GmbH
• Public title: EMPagliflozin outcomE tRial in patients with chrOnic heaRt failure EMPEROR-Preserved
• Scientific title: A phase III randomised, double-blind trial to evaluate efficacy and safety of once daily empagliflozin 10 mg compared to placebo, in patients with chronic Heart Failure with preserved Ejection Fraction (HFpEF).
• Date of first enrolment: 06/03/2017
• Target sample size: 4126
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002278-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, China, Colombia, Czech Republic, European Union, Germany, Hungary, India, Japan, Korea, Republic of, Lithuania, Mexico, Netherlands, Singapore, South Africa, Spain, United Kingdom, United States

Contacts

• Name: CT Disclosure & Data Transparency
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG

• Name: CT Disclosure & Data Transparency
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG

Key inclusion & exclusion criteria

Inclusion criteria:
- Patients with chronic HF diagnosed for at least 3 months before Visit 1 and currently in HF New York Heart Association (NYHA)class II-IV
- Chronic HF with preserved EF defined as LVEF > 40 % per local reading (obtained by echocardiography, radionuclide ventriculography, invasive angiography, MRI or CT), and no prior measurement of LVEF = 40% under stable conditions. The EF must have been obtained and documented at Visit 1 or within 6 months prior to Visit 1, and more than 90 days after any Myocardial Infarction.
- Elevated N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) > 300 pg/ml for patients without AF, OR > 900 pg/ml for patients with AF, analysed at the Central laboratory at Visit 1
- Patients must have at least one of the following evidence of HF:
a) Structural heart disease (left atrial enlargement and/or left ventricular hypertrophy) documented by echocardiogram at Visit 1,
OR
b) Documented hospitalisation for HF (HHF) within 12 months prior to Visit 1
- Oral diuretics, if prescribed to patient according to local guideline and discretion of the Investigator, should be stable for at least 1 week prior to Visit 2 (Randomisation)
- eGFR (CKD-EPI)cr = 20 mL/min/1.73m2 at Visit 1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2063
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2063

Exclusion criteria:
1. Myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to Visit 1
2. Heart transplant recipient or listed for heart transplant
3. Implantation of cardioverter defibrillator (ICD) within 3 months prior to Visit 1
4. Implanted cardiac resynchronisation therapy (CRT)
5. Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases, muscular dystrophies, cardiomyopathy with reversible causes, hypertrophic
obstructive cardiomyopathy or known pericardial constriction
6. Any severe valvular heart disease expected to lead to
surgery during the trial in the Investigator’s opinion
7. Acute decompensated HF requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device within 1 week from discharge to Visit 1, and during screening period until Visit 2 (Randomisation)
8. Atrial fibrillation or atrial flutter with a resting heart rate > 110 bpm documented by ECG at Visit 2 (Randomisation)
9. Systolic blood pressure (SBP) = 180 mmHg at Visit 2. If SBP >150 mmHg and <180 mmHg at Visit 2, the patient should be receiving at least 3 antihypertensive drugs
10. Symptomatic hypotension and/or a SBP < 100 mmHg at Visit 1 or Visit 2


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Heart failure (HF) with preserved ejection fraction (EF).
MedDRA version: 19.1 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849

Intervention(s)

Trade Name: Jardiance
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EMPAGLIFLOZIN
CAS Number: 864070-44-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10 -
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Time to first event of adjudicated CV death or adjudicated HHF in patients with Heart Failure with preserved Ejection Fraction (HFpEF).

Main Objective: To demonstrate superiority of empagliflozin 10 mg versus placebo in patients with symptomatic, chronic HF and preserved ejection fraction (LVEF > 40%) under stable treatment of HF symptoms.

Timepoint(s) of evaluation of this end point: Report time to event

Secondary Objective: Not applicable

Secondary Outcome(s)

Secondary end point(s): 1. Occurrence of adjudicated HHF (first and recurrent),
2. eGFR (CKD-EPI)cr slope of change from baseline

Other secondary endpoints:
- Time to first occurrence of sustained* reduction of =40% eGFR (CKD-EPI)cr or o sustained eGFR (CKD-EPI)cr <15 mL/min/1.73 m2 for patients with baseline eGFR =30 mL/min/1.73 m2 o sustained eGFR (CKD-EPI)cr <10 mL/min/1.73 m2 for patients with baseline eGFR <30 mL/min/1.73 m2
*An eGFR (CDK-EPI)cr reduction is considered sustained, if it is determined by two or more consecutive post-baseline central laboratory measurements separated by at least 30 days (first to last of the consecutive eGFR values).
- Time to first adjudicated HHF
- Time to adjudicated CV death
- Time to all-cause mortality
- Time to onset of DM (defined as HbA1c =6.5% or as diagnosed by the Investigator) in patients with pre-DM defined as no history of DM and no HbA1c =6.5 before treatment, and a pre-treatment HbA1c value of = 5.7 and <6.5
- Change from baseline in clinical summary score (HF symptoms and physical limitations domains) of the Kansas City Cardiomyopathy Questionnaire (KCCQ) at week 52
- Occurrence of all-cause hospitalisation (first and recurrent)

Timepoint(s) of evaluation of this end point: Report time to event

Secondary ID(s)

2016-002278-11-DE

1245.110

Source(s) of Monetary Support

Boehringer Ingelheim International GmbH

Ethics review

Status: Approved
Approval date: 27/02/2017
Contact: