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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03448419




Registration number
NCT03448419
Ethics application status
Date submitted
22/02/2018
Date registered
28/02/2018
Date last updated
27/11/2020

Titles & IDs
Public title
This Study Tests Empagliflozin in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF). 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 Reduced Ejection Fraction (HFrEF) (EMPERIAL-reduced)
Secondary ID [1] 0 0
2017-004073-14
Secondary ID [2] 0 0
1245-0168
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 -

Placebo 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 6-Minutes-Walking-Test (6MWT) Distance
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 6-Minutes-Walking-Test (6MWT) Distance
Timepoint [3] 0 0
At baseline and at week 6
Secondary outcome [4] 0 0
Change From Baseline to Week 12 in Clinical Congestion Score
Timepoint [4] 0 0
At baseline and at week 12
Secondary outcome [5] 0 0
Change From Baseline to Week 12 in Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms
Timepoint [5] 0 0
At baseline and at week 12
Secondary outcome [6] 0 0
Change From Baseline to Week 12 in Patient Global Impression of Severity (PGI-S) of Dyspnoea
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
At week 12
Secondary outcome [8] 0 0
Patient Global Impression of Change (PGI-C) in Dyspnea at Week 12
Timepoint [8] 0 0
At week 12
Secondary outcome [9] 0 0
Relative Change From Baseline to Week 12 in N-terminal Pro-brain Natriuretic Peptide (NTproBNP)
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 childbearing potential (WOCBP)1 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
* 6MWT distance =350 m at screening and at baseline.
* Patients with chronic HF diagnosed for at least 3 months before Visit 1 and currently in NYHA class II-IV
* Chronic HF with reduced EF defined as LVEF = 40 % as per echocardiography at Visit 1 as per local reading (obtained under stable condition).
* Elevated NT-proBNP > 450 pg/ml for patients without atrial fibrillation (AF) OR NTproBNP > 600 pg/ml for patients with AF as analysed at the Central laboratory at Visit 1
* Patients must be clinically stable and on appropriate and stable dose of medical therapy for HF (such as ACEi, ARB, ß-blocker, oral diuretics, MRA, ARNI, ivabradine), consistent with prevailing CV guidelines, stable for at least 4 weeks prior to Visit 1(screening) with the exception of diuretics which must have been stable for at least two weeks prior to Visit 1. The investigator must document the reason in case the patient is not on such medication or if not on target dose of any heart failure medication as per local guidelines.
* Clinically stable at randomization with no signs of heart failure decompensation (as per investigator judgement).
* Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines, and if a device is required, it must have been implanted for at least 3 months prior to visit 1 for CRT and 1 month prior to visit 1 for ICD.
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 TIA in past 90 days prior to Visit 1
* Acute decompensated HF (exacerbation of chronic HF) 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, 1245-0167)
* 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 SBP < 100 mmHg at Visit 1 or 2
* Systolic blood pressure (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.
* Planned implantation of ICD or CRT during the course of the trial.
* Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening
* Treatment with i.v. iron therapy or erythropoietin 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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
University of the Sunshine Coast - Birtinya
Recruitment hospital [4] 0 0
Cairns Base Hospital - Cairns
Recruitment hospital [5] 0 0
Peninsular Health CV Research Unit - Frankston
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
4575 - Birtinya
Recruitment postcode(s) [4] 0 0
4870 - Cairns
Recruitment postcode(s) [5] 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
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Mississippi
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New Jersey
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
South Dakota
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Wisconsin
Country [25] 0 0
Canada
State/province [25] 0 0
Alberta
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Germany
State/province [27] 0 0
Bamberg
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Germany
State/province [28] 0 0
Berlin
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Germany
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Bremen
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Germany
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Dresden
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Germany
State/province [31] 0 0
Düsseldorf
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Germany
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Esslingen
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Germany
State/province [33] 0 0
Frankfurt
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Germany
State/province [34] 0 0
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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Mainz
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Germany
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Ulm
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Germany
State/province [39] 0 0
Würzburg
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Greece
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Athens
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Greece
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Haidari, Athens
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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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Napoli
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Italy
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Palermo
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Italy
State/province [48] 0 0
Roma
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Norway
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Grålum
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Norway
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Hønefoss
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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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Lodz
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Pulawy
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Torun
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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
State/province [61] 0 0
Carnaxide
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Portugal
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Coimbra
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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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Penafiel
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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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L'Hospitalet de Llobregat
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Spain
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Madrid
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Spain
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Valencia
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Sweden
State/province [73] 0 0
Göteborg
Country [74] 0 0
Sweden
State/province [74] 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
Trial website
Trial related presentations / publications
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.