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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03448406




Registration number
NCT03448406
Ethics application status
Date submitted
22/02/2018
Date registered
28/02/2018
Date last updated
8/12/2020

Titles & IDs
Public title
This Study Tests Empagliflozin in Patients With Chronic Heart Failure With Preserved Ejection Fraction (HFpEF). The Study Looks at How Far Patients Can Walk in 6 Minutes and at Their Heart Failure Symptoms.
Scientific title
A Phase III Randomised, Double-blind Trial to Evaluate the Effect of 12 Weeks Treatment of Once Daily EMPagliflozin 10 mg Compared With Placebo on ExeRcise Ability and Heart Failure Symptoms, In Patients With Chronic HeArt FaiLure With Preserved Ejection Fraction (HFpEF) (EMPERIAL - Preserved)
Secondary ID [1] 0 0
2017-004072-59
Secondary ID [2] 0 0
1245-0167
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Empagliflozin
Treatment: Drugs - Placebo

Experimental: Empagliflozin -

Active comparator: Placebo -


Treatment: Drugs: Empagliflozin
Film-coated tablet

Treatment: Drugs: Placebo
Film-coated tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 12 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes in Standardised Conditions (6MWTD)
Timepoint [1] 0 0
At baseline and at Week 12
Secondary outcome [1] 0 0
Change From Baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS)
Timepoint [1] 0 0
At baseline and at Week 12
Secondary outcome [2] 0 0
Change From Baseline to Week 12 in Chronic Heart Failure Questionnaire Self- Administered Standardized Format (CHQ-SAS) Dyspnea Score
Timepoint [2] 0 0
At baseline and at Week 12
Secondary outcome [3] 0 0
Change From Baseline to Week 6 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes
Timepoint [3] 0 0
At baseline and at Week 6
Secondary outcome [4] 0 0
Change From Baseline in Clinical Congestion Score at Week 12
Timepoint [4] 0 0
At baseline and at Week 12
Secondary outcome [5] 0 0
Change From Baseline in Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms at Week 12
Timepoint [5] 0 0
At baseline and at Week 12
Secondary outcome [6] 0 0
Change From Baseline in Patient Global Impression of Severity (PGI-S) of Dyspnea Severity at Week 12
Timepoint [6] 0 0
At baseline and at Week 12
Secondary outcome [7] 0 0
Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms at Week 12
Timepoint [7] 0 0
Week 12
Secondary outcome [8] 0 0
Patient Global Impression of Change (PGI-C) in Dyspnea at Week 12
Timepoint [8] 0 0
Week 12
Secondary outcome [9] 0 0
Relative Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NTproBNP) at Week 12
Timepoint [9] 0 0
Within 3 weeks prior to treatment start and at Week 12.

Eligibility
Key inclusion criteria
* Of full age of consent (according to local legislation, usually = 18 years) at screening.
* Male or female patients. Women of child bearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per 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 is provided in the patient information.
* Signed and dated written informed consent in accordance with ICHGCP and local legislation prior to admission to the trial
* Six minute walk test (6MWT) distance =350 m at screening and at baseline.
* Patients with CHF diagnosed for at least 3 months before Visit 1, and currently in NYHA class II-IV
* Chronic heart failure (CHF) with preserved Ejection fraction (EF) defined as left ventricle ejection fraction(LVEF) > 40 % as per echocardiography at Visit 1 per local reading and no prior measurement of LVEF = 40% under stable conditions.
* Elevated N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) > 300 pg/ml for patients without atrial fibrillation (AF), OR > 600 pg/ml for patients with AF, as analysed at the Central laboratory at Visit 1
* Patients must have at least one of the following evidence of heart failure (HF):

* Structural heart disease (left atrial enlargement and/or left ventricular hypertrophy) documented by echocardiogram at Visit 1, OR
* Documented Hospitalization for Heart Failure (HHF) within 12 months prior to Visit 1
* Consistent with prevailing CV guidelines, if oral diuretics are prescribed to control symptoms, patients must be on an appropriate and stable dose of oral diuretics for at least 2 weeks prior to Visit 1 to control symptoms.
* Clinically stable at randomization with no signs of heart failure decompensation (as per investigator judgement).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Myocardial infarction (increase in cardiac enzymes in combination with symptoms of ischaemia or newly developed ischaemic ECG changes), coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or transient ischemic attack in past 90 days prior to Visit 1
* Acute decompensated HF (exacerbation of CHF) requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device within 4 weeks prior to Visit 1, and/or during screening period until Visit 2
* Previous or current randomisation in another Empagliflozin Heart Failure trial (i.e. studies 1245.110, 1245.121, 1245-0168)
* Type 1 Diabetes Mellitus (T1DM)
* Impaired renal function, defined as eGFR < 20 mL/min/1.73 m2 (CKD-EPIcr) or requiring dialysis, as determined at Visit 1
* Symptomatic hypotension or a systolic blood pressure (SBP) < 100 mmHg at Visit 1 or 2
* SBP = 180 mmHg at Visit 1 or 2, or SBP >160mmHg at both Visit 1 and 2
* Atrial fibrillation or atrial flutter with a resting heart rate > 110 bpm documented by ECG at Visit 1 (Screening)
* Unstable angina pectoris in past 30 days prior to Visit 1
* Largest distance walked in 6 minutes (6MWTD) at baseline <100m.
* Any presence of condition that precludes exercise testing such as:

* claudication,
* uncontrolled (according to investigator judgement) bradyarrhythmia or tachyarrhythmia,
* significant musculoskeletal disease,
* primary pulmonary hypertension,
* severe obesity (body mass index =40.0 kg/m2),
* orthopedic conditions that limit the ability to walk (such as arthritis in the leg, knee or hip injuries)
* amputation with artificial limb without stable prosthesis function for the past 3 months
* Any condition that in the opinion of the investigator would contraindicate the assessment of 6MWT
* Patients in a structured (according to Investigator judgement) exercise training program in the 1 month prior to screening or planned to start one during the course of this trial.
* ICD implantation within 1 month prior to Visit 1 or planned during the course of the trial
* Implanted cardiac resynchronisation therapy (CRT)
* Treatment with i.v. iron therapy or erythropoietin (EPO) within 3 months prior to screening.
* Further exclusion criteria applies

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/10/2019
Sample size
Target
Accrual to date
Final
315
Recruitment in Australia
Recruitment state(s)
ACT,QLD,VIC
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
University of the Sunshine Coast - Birtinya
Recruitment hospital [3] 0 0
Peninsular Health CV Research Unit - Frankston
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
4575 - Birtinya
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
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Florida
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United States of America
State/province [6] 0 0
Georgia
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United States of America
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Idaho
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United States of America
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Illinois
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United States of America
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Kansas
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United States of America
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Louisiana
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United States of America
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Massachusetts
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Michigan
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Missouri
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Nevada
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New Jersey
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United States of America
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New York
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United States of America
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North Carolina
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Ohio
Country [19] 0 0
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South Carolina
Country [20] 0 0
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South Dakota
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Tennessee
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Texas
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United States of America
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Virginia
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Canada
State/province [24] 0 0
Alberta
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Canada
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Ontario
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Germany
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Bamberg
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Düsseldorf
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Germany
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Frankfurt
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Germany
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Freiburg
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Germany
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Köln
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Germany
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Leipzig
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Germany
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Magdeburg
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Germany
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Mainz
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Germany
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Ulm
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Germany
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Würzburg
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Greece
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Athens
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Greece
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Chalkida
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Greece
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Herakleion, Crete
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Greece
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Ioannina
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Greece
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Thessaloniki
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Italy
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Milano
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Italy
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Mondovì (CN)
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Italy
State/province [45] 0 0
Napoli
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Italy
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Palermo
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Italy
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Roma
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Norway
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Grålum
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Norway
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Oslo
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Norway
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Stavanger
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Norway
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Trondheim
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Poland
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Bydgoszcz
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Poland
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Krakow
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Poland
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Lodz
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Poland
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Pulawy
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Poland
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Warsaw
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Poland
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Wroclaw
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Portugal
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Carnaxide
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Portugal
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Coimbra
Country [60] 0 0
Portugal
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Leiria
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Portugal
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Lisboa
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Portugal
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Porto
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Spain
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Alicante
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Spain
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Badalona
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Spain
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Granada
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Spain
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Madrid
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Spain
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Valencia
Country [68] 0 0
Sweden
State/province [68] 0 0
Göteborg
Country [69] 0 0
Sweden
State/province [69] 0 0
Lund
Country [70] 0 0
Sweden
State/province [70] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study is to evaluate the effect of empagliflozin 10 mg versus placebo on exercise ability using the 6 minute walk test (6MWT) in patients with chronic heart failure (CHF) with preserved ejection fraction (LVEF \> 40%).

Secondary objectives are to assess Patient-Reported Outcome (PRO)
Trial website
https://clinicaltrials.gov/study/NCT03448406
Trial related presentations / publications
Anker SD, Ponikowski P, Wanner C, Pfarr E, Hauske S, Peil B, Salsali A, Ritter I, Koitka-Weber A, Brueckmann M, Lindenfeld J, Abraham WT; EMPERIAL Investigators and National Coordinators. Kidney Function After Initiation and Discontinuation of Empagliflozin in Patients With Heart Failure With and Without Type 2 Diabetes: Insights From the EMPERIAL Trials. Circulation. 2021 Oct 12;144(15):1265-1267. doi: 10.1161/CIRCULATIONAHA.121.054669. Epub 2021 Aug 16. No abstract available. Erratum In: Circulation. 2022 Feb 22;145(8):e641. doi: 10.1161/CIR.0000000000001059.
Abraham WT, Ponikowski P, Brueckmann M, Zeller C, Macesic H, Peil B, Brun M, Ustyugova A, Jamal W, Salsali A, Lindenfeld J, Anker SD; EMPERIAL Investigators and National Coordinators. Rationale and design of the EMPERIAL-Preserved and EMPERIAL-Reduced trials of empagliflozin in patients with chronic heart failure. Eur J Heart Fail. 2019 Jul;21(7):932-942. doi: 10.1002/ejhf.1486. Epub 2019 Jun 19.
Nassif ME, Kosiborod M. Effects of sodium glucose cotransporter type 2 inhibitors on heart failure. Diabetes Obes Metab. 2019 Apr;21 Suppl 2:19-23. doi: 10.1111/dom.13678.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03448406