Heart Failure With Preserved Ejection Fraction (HFpEF)Phase 3NCT03877224

DETERMINE-preserved - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Preserved Ejection Fraction

A Phase 3 study testing Dapagliflozin in people with Heart Failure With Preserved Ejection Fraction (HFpEF), run by AstraZeneca at 101 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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 Preserved Ejection Fraction (HFpEF) Read more about this study

Who is it for?: Ages 40 to 150 years
Conditions the study is for: Heart Failure With Preserved Ejection Fraction (HFpEF)
What is being tested?: Dapagliflozin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 504 participants
Where: 101 sitesin 12 countries
Study dates: 4 Apr 2019to 9 Jul 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 150 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provision of signed informed consent prior to any study specific procedures
Male or female, aged ≥40 years
Established documented diagnosis of symptomatic HFpEF (NYHA functional class II-IV), which has been present for at least 8 weeks
LVEF>40% and evidence of structural heart disease
Elevated NT-proBNP levels
Patients should receive background standard of care as described below: All patients will be treated according to locally recognised guidelines on standard of care treatment for patients with HFpEF. Therapy should have been individually optimised and stable for ≥4 weeks (this does not apply to diuretics) and include (unless contraindicated or not tolerated) treatment of co morbidities (including high blood pressure, ischaemic heart disease, atrial fibrillation/flutter).
6MWD≥100 metres and ≤425 metres at enrolment and randomization

Who cannot join

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

Show all 13Show fewer

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 fibrillation/flutter, 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

Trial locations and contacts

101 sites in 12 countries.

Country

City, postcode or hospital

101 sites in 12 countries

United States25 sites

Research Site
Abington, Pennsylvania, 19001
Research Site
Alexander City, Alabama, 35010
Research Site
Annapolis, Maryland, 21401
Research Site
Arlington Heights, Illinois, 60005
Research Site
Beverly Hills, California, 90211
Research Site
Bossier City, Louisiana, 71111
Research Site
Burlington, North Carolina, 27215
Research Site
Cincinnati, Ohio, 45267
Research Site
Doylestown, Pennsylvania, 18901
Research Site
Fort Payne, Alabama, 35967
Research Site
Hazel Crest, Illinois, 60429
Research Site
Jacksonville, Florida, 32209
Research Site
Louisville, Kentucky, 40205
Research Site
Miami, Florida, 33133
Research Site
Miami, Florida, 33173
Research Site
Munster, Indiana, 46321
Research Site
New Brunswick, New Jersey, 08901
Research Site
Pittsburgh, Pennsylvania, 15212
Research Site
Ridgewood, New Jersey, 07450
Research Site
Rosedale, New York, 11422
Research Site
Seattle, Washington, 98101
Research Site
Spring, Texas, 77380
Research Site
Torrance, California, 90502
Research Site
Tucker, Georgia, 30084
Research Site
Winston-Salem, North Carolina, 27157

Other trials in United States

Canada18 sites

Research Site
Ajax, Ontario, L1Z 0B1
Research Site
Chicoutimi, Quebec, G7H 7K9
Research Site
Edmonton, Alberta, T5A 4L8
Research Site
Gatineau, Quebec, J8Y 6S8
Research Site
Guelph, Ontario, N1H 1B1
Research Site
Longueuil, Quebec, J4M 2X1
Research Site
Moncton, New Brunswick, E1G 1A7
Research Site
Montreal, Quebec, H2X 0A9
Research Site
Montreal, Quebec, H3G 1A4
Research Site
Mount Pearl, Newfoundland and Labrador, A1N 1W7
Research Site
North York, Ontario, M3M 3E5
Research Site
Québec, Quebec, G1G 3Y8
Research Site
Québec, Quebec, G2J 0C4
Research Site
Québec, Quebec, G3K 2P8
Research Site
Saint-Georges, Quebec, G5Y 4T8
Research Site
Scarborough Village, Ontario, M1E 5E9
Research Site
Scarborough Village, Ontario, M1P 2T7
Research Site
St. John's, Newfoundland and Labrador, A1B 3V6

Other trials in Canada

Denmark10 sites

Research Site
Århus N, 8200
Research Site
Copenhagen, 2300
Research Site
Esbjerg, 6700
Research Site
Hellerup, 2900
Research Site
Hjørring, 9800
Research Site
Hvidovre, 2650
Research Site
Næstved, 4700
Research Site
Odense C, 5000
Research Site
Randers, 8930
Research Site
Svendborg, DK-5700

Other trials in Denmark

Japan10 sites

Research Site
Akashi-shi, 674-0063
Research Site
Daito-shi, 574-0074
Research Site
Kasugai-shi, 487-0016
Research Site
Matsubara-shi, 580-0032
Research Site
Naha, 902-8511
Research Site
Ōmihachiman, 523-0082
Research Site
Osaka, 530-0001
Research Site
Shunan-shi, 745-0822
Research Site
Takarazuka-shi, 665-0873
Research Site
Toshima-ku, 171-0014

Other trials in Japan

Sweden7 sites

Research Site
Borås, 506 30
Research Site
Gothenburg, 413 45
Research Site
Lund, 222 21
Research Site
Östersund, 831 83
Research Site
Stockholm, 114 46
Research Site
Stockholm, 118 83
Research Site
Umeå, 90737

Other trials in Sweden

Italy6 sites

Research Site
Bergamo, 24127
Research Site
Milan, 20162
Research Site
Naples, 80131
Research Site
Palermo, 90127
Research Site
Roma, 00189
Research Site
San Giovanni Rotondo, 71013

Other trials in Italy

Brazil5 sites

Research Site
Blumenau, 89020-430
Research Site
Brasillia, 72145-450
Research Site
Porto Alegre, 91350-200
Research Site
São Paulo, 01141-020
Research Site
São Paulo, 05403-000

Other trials in Brazil

Slovakia5 sites

Research Site
Brezno, 97742
Research Site
Lučenec, 984 01
Research Site
Martin, 036 01
Research Site
Prešov, 080 01
Research Site
Ružomberok, 034 26

Other trials in Slovakia

South Korea5 sites

Research Site
Gangwon-do, 26426
Research Site
Gwangju, 61469
Research Site
Seongnam-si, 463-707
Research Site
Seoul, 03080
Research Site
Seoul, 03722

Other trials in South Korea

Bulgaria4 sites

Research Site
Plovdiv, 4003
Research Site
Sofia, 1000
Research Site
Sofia, 1407
Research Site
Veliko Tarnovo, 5000

Other trials in Bulgaria

Argentina3 sites

Research Site
CABA, C1425AGC
Research Site
Ciudad Autonoma de Buenos Aire, C1407GTN
Research Site
Ciudad Autonomade Buenos Aires, 1426

Other trials in Argentina

South Africa3 sites

Research Site
Cape Town, 7500
Research Site
Diepkloof, Soweto, 2013
Research Site
Pinelands, 7405

Other trials in South Africa

About this study

Official title: 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 Preserved Ejection Fraction

Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF)
Being tested: Dapagliflozin, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DapagliflozinDrug
Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.
PlaceboOther
Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.

Study groups in NCT03877224
Study group	Role	What they receive
Dapagliflozin	Experimental	Green, diamond shaped, film coated tablets 10 mg administered orally, once daily Receives: Drug: Dapagliflozin
Placebo	Placebo comparator	Green, diamond shaped, film coated tablets placebo administered orally, once daily Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
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. KCCQ-TSS incorporates symptom frequency (4 items) and symptom burden (3 items) domains into a single score. The score is transformed to a range of 0-100 (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 alive at the week 16 visit but without KCCQ-TSS values. All the data for the endpoint, except for death, collected during COVID-19, are set as missing and imputed same way as pre-COVID-19 missing data.
Measured: At baseline and at week 16 or death before week 16
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)
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. KCCQ-PLS incorporates 6 physical limitation items into a single score. The score is transformed to a range of 0-100 (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 week 16 visit but without KCCQ-PLS values. All the data for the endpoint, except for death, collected during COVID-19, are set as missing and imputed same way as pre-COVID-19 missing data.
Measured: At baseline and at week 16 or death before week 16
Change From Baseline in 6-minute Walk Distance (6MWD) at Week 16 (Larger Distances Represent Better Functional Capacity)
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.
Measured: At baseline and at week 16 or death before week 16

Secondary outcomes (1)

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).
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.
Measured: At baseline and at end of study or death before week 16.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Apr 20199 Jul 2020

First posted15 Mar 2019
Study start4 Apr 2019
Primary completion9 Jul 2020
Study completion9 Jul 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Heart Failure With Preserved Ejection Fraction (HFpEF)Studies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 504 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03877224
Sponsor's protocol ID: D169EC00001
Other IDs: 2018-003441-42, 2018
Status last verified: Nov 2021
First submitted: 21 Feb 2019
Last updated: 17 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Publications

Docherty KF, Buendia Lopez R, Folkvaljon F, Boer RA, Chen J, Hammarstedt A, Kitzman DW, Kosiborod MN, Langkilde AM, Reicher B, Senni M, Wilderang U, Verma S, Cowie MR, Solomon SD, McMurray JJV. Wearable Accelerometer-Derived Measures of Physical Activity in Heart Failure: Insights From the DETERMINE trials. J Card Fail. 2025 Apr;31(4):689-703. doi: 10.1016/j.cardfail.2024.10.439. Epub 2024 Nov 26.
PubMed 39603408
Docherty KF, Buendia Lopez R, Folkvaljon F, de Boer RA, Cowie MR, Hammarstedt A, Kitzman DW, Kosiborod MN, Langkilde AM, Reicher B, Senni M, Shah SJ, Verma S, Solomon SD, McMurray JJV. Effect of Dapagliflozin on Accelerometer-Based Measures of Physical Activity in Patients With Heart Failure: An Analysis of the DETERMINE Trials. Circ Heart Fail. 2024 Oct;17(10):e012349. doi: 10.1161/CIRCHEARTFAILURE.124.012349. Epub 2024 Aug 30.
PubMed 39212948
McMurray JJV, Docherty KF, de Boer RA, Hammarstedt A, Kitzman DW, Kosiborod MN, Maria Langkilde A, Reicher B, Senni M, Shah SJ, Wilderang U, Verma S, Solomon SD. Effect of Dapagliflozin Versus Placebo on Symptoms and 6-Minute Walk Distance in Patients With Heart Failure: The DETERMINE Randomized Clinical Trials. Circulation. 2024 Mar 12;149(11):825-838. doi: 10.1161/CIRCULATIONAHA.123.065061. Epub 2023 Dec 7.
PubMed 38059368

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 17 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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 Preserved Ejection Fraction
ClinicalTrials.gov ID: NCT03877224
Acronym / sponsor ID: D169EC00001
Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF)
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 504 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 4 Apr 2019 (actual)
Primary completion: 9 Jul 2020 (actual)
Study completion: 9 Jul 2020 (actual)
First posted: 15 Mar 2019 (actual)
Results: Posted 17 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Dapagliflozin	Experimental	Drug: DapagliflozinGreen, diamond shaped, film coated tablets 10 mg administered orally, once daily
Placebo	Placebo comparator	Other: PlaceboGreen, diamond shaped, film coated tablets placebo administered orally, once daily

Who may qualify

Ages: 40 to 150 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Provision of signed informed consent prior to any study specific procedures
Male or female, aged ≥40 years
Established documented diagnosis of symptomatic HFpEF (NYHA functional class II-IV), which has been present for at least 8 weeks
LVEF>40% and evidence of structural heart disease
Elevated NT-proBNP levels

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DapagliflozinTablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.	Drug	Dapagliflozin
PlaceboTablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.	Other	Placebo

Primary outcome

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
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. KCCQ-TSS incorporates symptom frequency (4 items) and symptom burden (3 items) domains into a single score. The score is transformed to a range of 0-100 (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 alive at the week 16 visit but without KCCQ-TSS values. All the data for the endpoint, except for death, collected during COVID-19, are set as missing and imputed same way as pre-COVID-19 missing data.
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
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. KCCQ-PLS incorporates 6 physical limitation items into a single score. The score is transformed to a range of 0-100 (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 week 16 visit but without KCCQ-PLS values. All the data for the endpoint, except for death, collected during COVID-19, are set as missing and imputed same way as pre-COVID-19 missing data.
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 before week 16
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.

1 secondary outcome

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.

Results and safety

Results posted to the registry on 17 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dapa 10 mg	253	248
Placebo	251	243

Primary outcome: 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. Median (Inter-Quartile Range). Unit: Score on a scale

Measure	Dapa 10mg n = 253	Placebo n = 251
Value	5.21 (-3.13 to 12.50)	1.04 (-5.73 to 15.10)

Dapa 10mg vs Placebo: Hodges-Lehmann median diff. vs placebo: 3.16 (95% CI 0.36 to 6.01), p = 0.07905, Rank ANCOVA

Population analysed: Full Analysis Set: All participants that were randomized, regardless of whether treated or not.

Primary outcome: 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. Median (Inter-Quartile Range). Unit: Score on a scale

Measure	Dapa 10mg n = 250	Placebo n = 250
Value	0.00 (-4.17 to 12.50)	0.00 (-8.33 to 12.50)

Dapa 10mg vs Placebo: Hodges-Lehmann median diff. vs placebo: 3.12 (95% CI -0.09 to 5.37), p = 0.23215, Rank ANCOVA

Population analysed: Full Analysis Set: All participants that were randomized, regardless of whether treated or not, excluding participants with non-calculable baseline or week 16 KCCQ-PLS.

Primary outcome: 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 before week 16. Median (Inter-Quartile Range). Unit: meters

Measure	Dapa 10mg n = 253	Placebo n = 251
Value	9.0 (-15.0 to 37.0)	8.5 (-14.5 to 35.5)

Dapa 10mg vs Placebo: Hodges-Lehmann median diff. vs placebo: 1.6 (95% CI -5.9 to 9.0), p = 0.66801, Rank ANCOVA

Population analysed: Full Analysis Set: All participants that were randomized, regardless of whether treated or not.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Includes data collected on or after date of first dose and up to (including) 30 days following last dose of randomized study drug, and no later than visit 5 (up to day 119). Deaths collected on or after first dose of randomized study drug, up to 119 days.. Other adverse events reported at 0.05% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dapa 10 mg	26 of 252 (10.3%)	0 of 252 (0%)	3 of 252
Placebo	19 of 249 (7.6%)	0 of 249 (0%)	2 of 249

Limitations and caveats (from the sponsor): In this study, a subset of participants received wearable activity monitors to wear at home for 3 periods of 7 days. Data collection from the wearable device was challenging and a substantial amount of data was missing. This limits the use of the data based on the wearable activity monitors to investigate the potential impact of study drug on the amount, duration, and intensity of physical activity.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39603408Docherty KF, Buendia Lopez R, Folkvaljon F, Boer RA, Chen J, Hammarstedt A, Kitzman DW, Kosiborod MN, Langkilde AM, Reicher B, Senni M, Wilderang U, Verma S, Cowie MR, Solomon SD, McMurray JJV. Wearable Accelerometer-Derived Measures of Physical Activity in Heart Failure: Insights From the DETERMINE trials. J Card Fail. 2025 Apr;31(4):689-703. doi: 10.1016/j.cardfail.2024.10.439. Epub 2024 Nov 26.
Derived from this study: PubMed 39212948Docherty KF, Buendia Lopez R, Folkvaljon F, de Boer RA, Cowie MR, Hammarstedt A, Kitzman DW, Kosiborod MN, Langkilde AM, Reicher B, Senni M, Shah SJ, Verma S, Solomon SD, McMurray JJV. Effect of Dapagliflozin on Accelerometer-Based Measures of Physical Activity in Patients With Heart Failure: An Analysis of the DETERMINE Trials. Circ Heart Fail. 2024 Oct;17(10):e012349. doi: 10.1161/CIRCHEARTFAILURE.124.012349. Epub 2024 Aug 30.
Derived from this study: PubMed 38059368McMurray JJV, Docherty KF, de Boer RA, Hammarstedt A, Kitzman DW, Kosiborod MN, Maria Langkilde A, Reicher B, Senni M, Shah SJ, Wilderang U, Verma S, Solomon SD. Effect of Dapagliflozin Versus Placebo on Symptoms and 6-Minute Walk Distance in Patients With Heart Failure: The DETERMINE Randomized Clinical Trials. Circulation. 2024 Mar 12;149(11):825-838. doi: 10.1161/CIRCULATIONAHA.123.065061. Epub 2023 Dec 7.
Clinical Study ProtocolLink provided by the sponsor.
Statistical Analysis PlanLink provided by the sponsor.
CSR synopsisLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

101 sites in 12 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dapagliflozin in people with Heart Failure With Preserved Ejection Fraction (HFpEF), run by AstraZeneca at 101 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 101 sites in United States, Canada, Denmark, Japan, Sweden and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03877224, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2021.