- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03877237
DETERMINE-reduced - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Reduced Ejection Fraction
International, Multicentre, Parallel-group, Randomised, Double-blind, Placebo-controlled, Phase III Study Evaluating the Effect of Dapagliflozin on Exercise Capacity in Heart Failure Patients With Reduced Ejection Fraction
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Blumenau, Brazil, 89020-430
- Research Site
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Porto Alegre, Brazil, 91350-200
- Research Site
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Sao Paulo, Brazil, 01141-020
- Research Site
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São Paulo, Brazil, 05403-000
- Research Site
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Quebec, Canada, G3K 2P8
- Research Site
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Quebec, Canada, G2J 0C4
- Research Site
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Quebec, Canada, G1G 3Z4
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Manitoba
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Winnipeg, Manitoba, Canada, R2H 2A6
- Research Site
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New Brunswick
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Moncton, New Brunswick, Canada, E1G 1A7
- Research Site
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Newfoundland and Labrador
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St. John's, Newfoundland and Labrador, Canada, A1B 3V6
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Ontario
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Ajax, Ontario, Canada, L1Z 0B1
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North York, Ontario, Canada, M3M 3E5
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Oshawa, Ontario, Canada, L1J 2K1
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Scarborough, Ontario, Canada, M1E 5E9
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Stoney Creek, Ontario, Canada, L8J 3W2
- Research Site
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York, Ontario, Canada, M9N 1W4
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Quebec
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Gatineau, Quebec, Canada, J8Y 6S8
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Longueuil, Quebec, Canada, J4M 2X1
- Research Site
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Montreal, Quebec, Canada, H2X 0A9
- Research Site
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St-Georges, Quebec, Canada, G5Y 4T8
- Research Site
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Esbjerg, Denmark, 6700
- Research Site
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Hellerup, Denmark, 2900
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Hjørring, Denmark, 9800
- Research Site
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Hvidovre, Denmark, 2650
- Research Site
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København, Denmark, 2300
- Research Site
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Næstved, Denmark, 4700
- Research Site
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Odense C, Denmark, 5000
- Research Site
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Randers, Denmark, 8930
- Research Site
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Svendborg, Denmark, DK-5700
- Research Site
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Århus N, Denmark, 8200
- Research Site
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Daito-shi, Japan, 574-0074
- Research Site
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Kobe-shi, Japan, 654-0155
- Research Site
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Matsubara-shi, Japan, 580-0032
- Research Site
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Naha, Japan, 902-8511
- Research Site
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Osaka-shi, Japan, 530-0001
- Research Site
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Sayama-shi,, Japan, 350-1305
- Research Site
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Shunan-shi, Japan, 745-0822
- Research Site
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Takarazuka-shi, Japan, 665-0873
- Research Site
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Gangwon-do, Korea, Republic of, 26426
- Research Site
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Seoul, Korea, Republic of, 03722
- Research Site
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Seoul, Korea, Republic of, 03080
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Lucenec, Slovakia, 984 01
- Research Site
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Martin, Slovakia, 036 01
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Presov, Slovakia, 080 01
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Cape Town, South Africa, 7500
- Research Site
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Cape Town, South Africa, 7405
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Diepkloof, Soweto, South Africa, 2013
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Göteborg, Sweden, 413 45
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Lund, Sweden, 222 21
- Research Site
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Ostersund, Sweden, 831 83
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Stockholm, Sweden, 118 83
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Stockholm, Sweden, 114 46
- Research Site
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Umeå, Sweden, 90737
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Alabama
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Alexander City, Alabama, United States, 35010
- Research Site
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Fairhope, Alabama, United States, 36532
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Fort Payne, Alabama, United States, 35967
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Mobile, Alabama, United States, 36608
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California
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Beverly Hills, California, United States, 90211
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Torrance, California, United States, 90502
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Connecticut
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Stamford, Connecticut, United States, 06905
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Florida
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Miami, Florida, United States, 33173
- Research Site
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Miami, Florida, United States, 33133
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Georgia
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Tucker, Georgia, United States, 30084
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Indiana
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Munster, Indiana, United States, 46321
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Michigan
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Petoskey, Michigan, United States, 49770
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Missouri
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Kansas City, Missouri, United States, 64111
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New Jersey
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New Brunswick, New Jersey, United States, 08901
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New York
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Buffalo, New York, United States, 14215
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New York, New York, United States, 10001
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Rosedale, New York, United States, 11422
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North Carolina
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Burlington, North Carolina, United States, 27215
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Pennsylvania
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Abington, Pennsylvania, United States, 19001
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Pittsburgh, Pennsylvania, United States, 15212
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Tennessee
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Tullahoma, Tennessee, United States, 37388
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Virginia
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Falls Church, Virginia, United States, 22042
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Washington
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Seattle, Washington, United States, 98101
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Provision of signed informed consent prior to any study specific procedures
- Male or female, aged ≥18 years
- Documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV), which has been present for at least 8 weeks
- LVEF≤40%
- Elevated NT-proBNP levels
Patients should receive background standard of care as described below: All HFrEF patients should be treated according to locally recognised guidelines on standard of care treatment with both drugs and devices, as appropriate. Guideline-recommended medications should be used at recommended doses unless contraindicated or not tolerated. Therapy should have been individually optimised and stable for ≥4 weeks (this does not apply to diuretics) before visit 1 and include (unless contraindicated or not tolerated):
- an ACE inhibitor, or ARB or sacubitril/valsartan and
- a beta-blocker and
- if considered appropriate by the patient's treating physician; a mineral corticoid receptor antagonist
- 6MWD≥100 metres and ≤425 metres at enrolment and randomization.
Exclusion Criteria:
- Presence of any condition that precludes exercise testing
- Participation in a structured exercise training programme in the 1 month prior to screening or planned to start during the trial
- Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
- Type 1 diabetes mellitus
- eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at enrolment, unstable or rapidly progressing renal disease at time of randomisation
- Systolic BP <95 mmHg on 2 consecutive measurements
- Systolic BP ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements
- Current acute decompensated HF or hospitalisation due to decompensated HF <4 weeks prior to enrolment
- MI, unstable angina, coronary revascularization ablation of atrial flutter/fibrillation, valve repair/replacement, implantation of a cardiac resynchronization therapy device within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization.
- Stroke or transient ischemic attack within 12 weeks prior to enrolment.
- Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
- Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization
- HF due to infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, or uncorrected primary valvular disease
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dapagliflozin
Green, diamond shaped, film coated tablets 10 mg administered orally, once daily
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Tablets administered orally once daily.
Treatment start within 24h after randomisation for 16 weeks.
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Placebo Comparator: Placebo
Green, diamond shaped, film coated tablets placebo administered orally, once daily
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Tablets administered orally once daily.
Treatment start within 24h after randomisation for 16 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Kansas-City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 16 (Higher Scores Represent Less HF Symptom Frequency and Burden).
Time Frame: At baseline and at week 16 or death before week 16
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Change from baseline in KCCQ-TSS was defined as the endpoint value at week 16 minus the baseline value.
KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.
The KCCQ-TSS incorporates the symptom frequency (4 items) and symptom burden (3 items) domains into a single summary score.
The score is transformed to a range of 0-100, in which a higher score reflects better health status.
Baseline value is the last value on or prior to the randomization visit.
Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive.
In rank ANCOVA and HL estimation, multiple imputation was performed on missing values for participants who were alive at the visit at week 16 but did not have KCCQ-TSS values.
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At baseline and at week 16 or death before week 16
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Change From Baseline in Kansas-City Cardiomyopathy Questionnaire-Physical Limitation Score (KCCQ-PLS) at Week 16 (Higher Scores Represent Less Physical Limitation Due to HF)
Time Frame: At baseline and at week 16 or death before week 16
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Change from baseline in KCCQ-PLS was defined as the endpoint value at week 16 minus the baseline value.
KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.
The KCCQ-PLS incorporates the 6 physical limitation items into a single score.
The score is transformed to a range of 0-100, in which a higher score reflects better health status.
Baseline value is the last value on or prior to the randomization visit.
Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive.
Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive.
In rank ANCOVA and HL estimation, multiple imputation was performed on missing values for participants who were alive at the visit at week 16 but did not have KCCQ-PLS values.
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At baseline and at week 16 or death before week 16
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Change From Baseline in 6-minute Walk Distance (6MWD) at Week 16 (Larger Distances Represent Better Functional Capacity).
Time Frame: At baseline and at week 16 or death prior to week 16
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Change from baseline in 6-minute walk distance (6MWD) (exercise capacity) at week 16 was defined as the distance walked in 6 minutes at week 16 minus the baseline value.
Baseline value is the last value on or prior to the randomization visit.
Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive.
In rank ANCOVA and HL estimation, multiple imputation was performed on missing values for participants who were alive at the visit at week 16 but did not have 6MWD values.
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At baseline and at week 16 or death prior to week 16
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline at the End of the Study in the Total Time Spent in Light to Vigorous Physical Activity, as Assessed Using a Wearable Activity Monitor (Accelerometer).
Time Frame: At baseline and at end of study or death before week 16.
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Change from baseline at the end of the study in total time spent in light to vigorous physical activity (LVPA), as assessed using a wearable activity monitor, was defined as the total time [per day] spent in LVPA at the end of the study minus the baseline value.
Baseline is the 7 day period starting on the day of enrolment and ending before randomization.
End of study is defined as the period starting on the day of week 14 and prior to the week 16 visit.
Deaths are treated as the worst outcome and ordering among deaths is based on last value while alive.
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At baseline and at end of study or death before week 16.
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D169EC00002
- 2018-003442-16 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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