Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/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.
Query!
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)
Query!
Secondary ID [1]
0
0
2017-004072-59
Query!
Secondary ID [2]
0
0
1245-0167
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Heart Failure
0
0
Query!
Condition category
Condition code
Cardiovascular
0
0
0
0
Query!
Coronary heart disease
Query!
Cardiovascular
0
0
0
0
Query!
Other cardiovascular diseases
Query!
Intervention/exposure
Study type
Interventional
Query!
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
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
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)
Query!
Assessment method [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). If repeated 6-minutes walk test (6MWT) measurements were available for the same day, the longest distance was used for analysis. Change from baseline was defined as the distance walked in 6 minutes at Week 12 minus the baseline value.
Baseline value was defined as the last available measurement before start of treatment with randomised study medication. If a participant was present at the visit at Week 12 but did not perform the 6MWT, the participant was evaluated as having walked a distance of 0 meter. If no value was available for Week 12, an imputed value was used. Patients with missing week 12 data who had no clinical event were ranked below any patient with non-missing data, but above the patients who had clinical events. Patients who died before week 12 were ranked below the patients in all categories above.
Query!
Timepoint [1]
0
0
At baseline and at Week 12
Query!
Secondary outcome [1]
0
0
Change From Baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS)
Query!
Assessment method [1]
0
0
Change from baseline in KCCQ-TSS was defined as the endpoint value at week 12 minus the last available measurement before start of treatment with randomised study medication. The KCCQ is 23 item self-administered questionnaire and comprises 7 domains: physical limitation, symptom frequency, symptom burden, symptom stability, social limitation, self-efficacy and quality of life. Additionally 3 summary scores exist: TSS, clinical summary score, and overall summary score. The scores of the KCCQ domains and summary scores range from 0 to 100, with higher score indicating better outcome. If no questionnaire was available at week 12, an imputed value was used. Patients with missing week 12 data who had no clinical event were ranked below any patient with non-missing data, but above the patients who had clinical events. Patients who died before week 12 were ranked below the patients in all categories above. If no questionnaire was available at baseline, change from baseline was not imputed.
Query!
Timepoint [1]
0
0
At baseline and at Week 12
Query!
Secondary outcome [2]
0
0
Change From Baseline to Week 12 in Chronic Heart Failure Questionnaire Self- Administered Standardized Format (CHQ-SAS) Dyspnea Score
Query!
Assessment method [2]
0
0
Change from baseline in CHQ-SAS was defined as the endpoint value at week 12 minus the last available endpoint value before start of treatment with randomised study medication. The CHQ-SAS evaluates 3 domains: dyspnoea, fatigue, and emotional function. Scores of the domains range from 1 to 7, with higher score indicating better quality of life. If no questionnaire was available at week 12, an imputed value was used. Patients with missing week 12 data who had no clinical event were ranked below any patient with non-missing data, but above the patients who had clinical events. Patients who died before week 12 were ranked below the patients in all categories above. If no questionnaire was available at baseline, change from baseline was not imputed.
Query!
Timepoint [2]
0
0
At baseline and at Week 12
Query!
Secondary outcome [3]
0
0
Change From Baseline to Week 6 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes
Query!
Assessment method [3]
0
0
Change from baseline to week 6 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions. Change from baseline was defined as the distance walked in 6 minutes at Week 6 minus the baseline value. Baseline value was defined as the last available measurement before start of treatment with randomised study medication.
If a participant was present at the visit at Week 6 but did not perform the 6-Minuted Walking Test, the participant was evaluated as having walked a distance of 0 meter. If no value was available for Week 6, an imputed value was used.
Query!
Timepoint [3]
0
0
At baseline and at Week 6
Query!
Secondary outcome [4]
0
0
Change From Baseline in Clinical Congestion Score at Week 12
Query!
Assessment method [4]
0
0
Change from baseline to week 12 in Clinical Congestion score is defined as the score-value at week 12 minus the score-value at baseline. Baseline value was defined as the last available measurement before start of treatment with randomised study medication. The Clinical Congestion Score (summary score) is based on 3 items: orthopnoea, jugular venous distention (JVD) and oedema. Each item was assessed through a 4-measure questionnaire, which was further converted to a standardised 4-point scale ranging from 0 to 3, with 0 indicating no or fewer symptoms and 3 indicating continous or more symptoms. If at least 2 of the 3 items are not missing, the summary score is calculated as: (average over items JVD, orthopnea and oedema actually answered)*3. The summary score ranges from 0 to 9, with lower value indicating better health, and higher value indicating worse health. Mean is adjusted mean.
Query!
Timepoint [4]
0
0
At baseline and at Week 12
Query!
Secondary outcome [5]
0
0
Change From Baseline in Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms at Week 12
Query!
Assessment method [5]
0
0
Change from baseline to week 12 in PGI-S of Heart Failure Symptoms. The Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms is a 1-item questionnaire to assess the patient's impression of symptoms severity, specifically: shortness of breath, fatigue and swelling. The PGI-S asks the Patient to choose one response that best describes how his/her heart failure symptoms, specifically: shortness of breath, fatigue and swelling are now on a 5-category scale, ranging from 'Not at all' (1) to 'Very severe' (5). Number of participants by change in score are reported. Change in score was defined as the number of categories improved/deteriorated from baseline to week 12.
Query!
Timepoint [5]
0
0
At baseline and at Week 12
Query!
Secondary outcome [6]
0
0
Change From Baseline in Patient Global Impression of Severity (PGI-S) of Dyspnea Severity at Week 12
Query!
Assessment method [6]
0
0
Change from baseline to week 12 in Patient Global Impression of Severity (PGI-S) of dyspnoea. The PGI-S of Dyspnoea is a 1-item questionnaire designed to assess the participant´s impression of symptom severity, specifically dyspnoea. The PGI-S item asks the participant to choose one response that best describes how his/her dyspnoea is now on a 5-category scale, ranging from 'Not at all' (1) to 'Very severe' (5). Number of participants by change in score are reported. Change in score was defined as the number of categories improved/deteriorated from baseline to week 12.
Query!
Timepoint [6]
0
0
At baseline and at Week 12
Query!
Secondary outcome [7]
0
0
Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms at Week 12
Query!
Assessment method [7]
0
0
The Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms is a 1-item questionnaire to assess the patient's impression of change in heart failure symptoms, specifically: shortness of breath, fatigue, and swelling. The PGI-C asks the patient to choose one Response that best describes the overall change (if any) in his/her heart failure symptoms, specifically: shortness of breath, fatigue, and swelling since he/she started taking the study medication on a 7- category scale ranging from 'Very much better' (+3) to 'Very much worse' (-3).
Query!
Timepoint [7]
0
0
Week 12
Query!
Secondary outcome [8]
0
0
Patient Global Impression of Change (PGI-C) in Dyspnea at Week 12
Query!
Assessment method [8]
0
0
The PGI-C in Dyspnoea is a 1-item questionnaire designed to assess the patient's Impression of change in dyspnoea. The PGI-C asks the patient to choose one response that best describes the change (if any) in his/her shortness of breath when performing usual activities since he/she started taking the study medication on a 7-category scale ranging from 'Very much better' (+3) to 'Very much worse' (-3).
Query!
Timepoint [8]
0
0
Week 12
Query!
Secondary outcome [9]
0
0
Relative Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NTproBNP) at Week 12
Query!
Assessment method [9]
0
0
Relative change from baseline to week 12 in N-terminal pro-brain natriuretic peptide (NTproBNP). Relative change from baseline is expressed as ratio of week 12 to baseline. Baseline value was defined as the mean of all available measurements from the screening visit until start of treatment with randomised study medication. Mean is adjusted mean.
Query!
Timepoint [9]
0
0
Within 3 weeks prior to treatment start and at Week 12.
Query!
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).
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
20/03/2018
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
9/10/2019
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
315
Query!
Recruitment in Australia
Recruitment state(s)
ACT,QLD,VIC
Query!
Recruitment hospital [1]
0
0
Canberra Hospital - Garran
Query!
Recruitment hospital [2]
0
0
University of the Sunshine Coast - Birtinya
Query!
Recruitment hospital [3]
0
0
Peninsular Health CV Research Unit - Frankston
Query!
Recruitment postcode(s) [1]
0
0
2605 - Garran
Query!
Recruitment postcode(s) [2]
0
0
4575 - Birtinya
Query!
Recruitment postcode(s) [3]
0
0
3199 - Frankston
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Alabama
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Colorado
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Connecticut
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Florida
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Georgia
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Idaho
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Illinois
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Kansas
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Louisiana
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Massachusetts
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Michigan
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Missouri
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Nevada
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
New Jersey
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
New York
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
North Carolina
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
Ohio
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
South Carolina
Query!
Country [20]
0
0
United States of America
Query!
State/province [20]
0
0
South Dakota
Query!
Country [21]
0
0
United States of America
Query!
State/province [21]
0
0
Tennessee
Query!
Country [22]
0
0
United States of America
Query!
State/province [22]
0
0
Texas
Query!
Country [23]
0
0
United States of America
Query!
State/province [23]
0
0
Virginia
Query!
Country [24]
0
0
Canada
Query!
State/province [24]
0
0
Alberta
Query!
Country [25]
0
0
Canada
Query!
State/province [25]
0
0
Ontario
Query!
Country [26]
0
0
Germany
Query!
State/province [26]
0
0
Bamberg
Query!
Country [27]
0
0
Germany
Query!
State/province [27]
0
0
Berlin
Query!
Country [28]
0
0
Germany
Query!
State/province [28]
0
0
Dresden
Query!
Country [29]
0
0
Germany
Query!
State/province [29]
0
0
Düsseldorf
Query!
Country [30]
0
0
Germany
Query!
State/province [30]
0
0
Frankfurt
Query!
Country [31]
0
0
Germany
Query!
State/province [31]
0
0
Freiburg
Query!
Country [32]
0
0
Germany
Query!
State/province [32]
0
0
Köln
Query!
Country [33]
0
0
Germany
Query!
State/province [33]
0
0
Leipzig
Query!
Country [34]
0
0
Germany
Query!
State/province [34]
0
0
Magdeburg
Query!
Country [35]
0
0
Germany
Query!
State/province [35]
0
0
Mainz
Query!
Country [36]
0
0
Germany
Query!
State/province [36]
0
0
Ulm
Query!
Country [37]
0
0
Germany
Query!
State/province [37]
0
0
Würzburg
Query!
Country [38]
0
0
Greece
Query!
State/province [38]
0
0
Athens
Query!
Country [39]
0
0
Greece
Query!
State/province [39]
0
0
Chalkida
Query!
Country [40]
0
0
Greece
Query!
State/province [40]
0
0
Herakleion, Crete
Query!
Country [41]
0
0
Greece
Query!
State/province [41]
0
0
Ioannina
Query!
Country [42]
0
0
Greece
Query!
State/province [42]
0
0
Thessaloniki
Query!
Country [43]
0
0
Italy
Query!
State/province [43]
0
0
Milano
Query!
Country [44]
0
0
Italy
Query!
State/province [44]
0
0
Mondovì (CN)
Query!
Country [45]
0
0
Italy
Query!
State/province [45]
0
0
Napoli
Query!
Country [46]
0
0
Italy
Query!
State/province [46]
0
0
Palermo
Query!
Country [47]
0
0
Italy
Query!
State/province [47]
0
0
Roma
Query!
Country [48]
0
0
Norway
Query!
State/province [48]
0
0
Grålum
Query!
Country [49]
0
0
Norway
Query!
State/province [49]
0
0
Oslo
Query!
Country [50]
0
0
Norway
Query!
State/province [50]
0
0
Stavanger
Query!
Country [51]
0
0
Norway
Query!
State/province [51]
0
0
Trondheim
Query!
Country [52]
0
0
Poland
Query!
State/province [52]
0
0
Bydgoszcz
Query!
Country [53]
0
0
Poland
Query!
State/province [53]
0
0
Krakow
Query!
Country [54]
0
0
Poland
Query!
State/province [54]
0
0
Lodz
Query!
Country [55]
0
0
Poland
Query!
State/province [55]
0
0
Pulawy
Query!
Country [56]
0
0
Poland
Query!
State/province [56]
0
0
Warsaw
Query!
Country [57]
0
0
Poland
Query!
State/province [57]
0
0
Wroclaw
Query!
Country [58]
0
0
Portugal
Query!
State/province [58]
0
0
Carnaxide
Query!
Country [59]
0
0
Portugal
Query!
State/province [59]
0
0
Coimbra
Query!
Country [60]
0
0
Portugal
Query!
State/province [60]
0
0
Leiria
Query!
Country [61]
0
0
Portugal
Query!
State/province [61]
0
0
Lisboa
Query!
Country [62]
0
0
Portugal
Query!
State/province [62]
0
0
Porto
Query!
Country [63]
0
0
Spain
Query!
State/province [63]
0
0
Alicante
Query!
Country [64]
0
0
Spain
Query!
State/province [64]
0
0
Badalona
Query!
Country [65]
0
0
Spain
Query!
State/province [65]
0
0
Granada
Query!
Country [66]
0
0
Spain
Query!
State/province [66]
0
0
Madrid
Query!
Country [67]
0
0
Spain
Query!
State/province [67]
0
0
Valencia
Query!
Country [68]
0
0
Sweden
Query!
State/province [68]
0
0
Göteborg
Query!
Country [69]
0
0
Sweden
Query!
State/province [69]
0
0
Lund
Query!
Country [70]
0
0
Sweden
Query!
State/province [70]
0
0
Stockholm
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Boehringer Ingelheim
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/Industry
Query!
Name [1]
0
0
Eli Lilly and Company
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
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)
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT03448406
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03448406
Download to PDF