Last reviewed · How we verify

NCT03877224

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

Completed Phase 3 Results posted Last updated 17 November 2021
What this trial tests

Phase 3 trial testing Dapagliflozin in Heart Failure With Preserved Ejection Fraction (HFpEF) in 504 participants. Completed in 9 July 2020.

Timeline
4 April 2019
Primary endpoint
9 July 2020
9 July 2020

Quick facts

Lead sponsorAstraZeneca
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment504
Start date4 April 2019
Primary completion9 July 2020
Estimated completion9 July 2020
Sites101 locations across Denmark, Italy, Japan, Slovakia, South Africa, Sweden, South Korea, Argentina

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 40 to 150, any sex, with Heart Failure With Preserved Ejection Fraction (HFpEF). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · 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 th

GroupValue95% CI
Dapa 10mg5.21-3.13 – 12.50
Placebo1.04-5.73 – 15.10
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) Primary · 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 de

GroupValue95% CI
Dapa 10mg0.00-4.17 – 12.50
Placebo0.00-8.33 – 12.50
Change From Baseline in 6-minute Walk Distance (6MWD) at Week 16 (Larger Distances Represent Better Functional Capacity) Primary · 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.

GroupValue95% CI
Dapa 10mg9.0-15.0 – 37.0
Placebo8.5-14.5 – 35.5
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). Secondary · At baseline and at end of study or death before week 16.

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.

GroupValue95% CI
Dapa 10mg-0.06-0.63 – 0.44
Placebo-0.07-0.67 – 0.13

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 0.05%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dapa 10 mg
Serious: 26/252 (10%)
Deaths: 3/252
Placebo
Serious: 19/249 (8%)
Deaths: 2/249

Serious adverse events (36 terms)

ReactionSystemDapa 10 mgPlacebo
Cardiac failureCardiac disorders
Urinary tract infectionInfections and infestations
PneumoniaInfections and infestations
Atrial fibrillationCardiac disorders
Cardiac failure acuteCardiac disorders
Cardiac failure congestiveCardiac disorders
Skin lacerationInjury, poisoning and procedural complications
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Acute left ventricular failureCardiac disorders
Acute myocardial infarctionCardiac disorders
Cardiac arrestCardiac disorders
Cardiopulmonary failureCardiac disorders
Conduction disorderCardiac disorders
Sinus node dysfunctionCardiac disorders
Ventricular fibrillationCardiac disorders
Ventricular tachycardiaCardiac disorders
Hiatus herniaGastrointestinal disorders
DeathGeneral disorders
CholelithiasisHepatobiliary disorders
Clostridial infectionInfections and infestations
InfluenzaInfections and infestations
FallInjury, poisoning and procedural complications
Post procedural haematuriaInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders

Most-reported serious reactions: Cardiac failure, Urinary tract infection, Pneumonia, Atrial fibrillation, Cardiac failure acute, Cardiac failure congestive, Skin laceration, Chronic obstructive pulmonary disease.

Data from ClinicalTrials.gov NCT03877224 adverse events section.

Sponsor's own description

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)

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Chronic low-grade inflammation in heart failure with preserved ejection fraction.
    Mesquita T, Lin YN, Ibrahim A. · · 2021 · cited 77× · PMID 34382743 · DOI 10.1111/acel.13453
  2. Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects.
    Palmiero G, Cesaro A, Vetrano E, Pafundi PC, et al · · 2021 · cited 72× · PMID 34070765 · DOI 10.3390/ijms22115863
  3. The Pleiotropic Effects of Sodium-Glucose Cotransporter-2 Inhibitors: Beyond the Glycemic Benefit.
    Patel DK, Strong J. · · 2019 · cited 62× · PMID 31456166 · DOI 10.1007/s13300-019-00686-z
  4. Effect of Dapagliflozin Versus Placebo on Symptoms and 6-Minute Walk Distance in Patients With Heart Failure: The DETERMINE Randomized Clinical Trials.
    McMurray JJV, Docherty KF, de Boer RA, Hammarstedt A, et al · · 2024 · cited 36× · PMID 38059368 · DOI 10.1161/circulationaha.123.065061
  5. Design and rationale of the EMPA-VISION trial: investigating the metabolic effects of empagliflozin in patients with heart failure.
    Hundertmark MJ, Agbaje OF, Coleman R, George JT, et al · · 2021 · cited 24× · PMID 33960149 · DOI 10.1002/ehf2.13406
  6. DAPA-HF trial: dapagliflozin evolves from a glucose-lowering agent to a therapy for heart failure.
    Kaplinsky E. · · 2020 · cited 22× · PMID 32165892 · DOI 10.7573/dic.2019-11-3
  7. Effects of SGLT2 inhibitors on cardiac function and health status in chronic heart failure: a systematic review and meta-analysis.
    Chen J, Jiang C, Guo M, Zeng Y, et al · · 2024 · cited 21× · PMID 38172861 · DOI 10.1186/s12933-023-02042-9
  8. Sodium-Glucose Cotransporter 2 Inhibitors and Heart Failure: A Bedside-to-Bench Journey.
    Cappetta D, De Angelis A, Bellocchio G, Telesca M, et al · · 2021 · cited 18× · PMID 35004918 · DOI 10.3389/fcvm.2021.810791

Verify or expand the search:

Other trials of Dapagliflozin

Trials testing the same drug.

Other recruiting trials for Heart Failure With Preserved Ejection Fraction (HFpEF)

Currently open trials in the same condition.

Other AstraZeneca trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03877224.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing