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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03877224
Other study ID # D169EC00001
Secondary ID 2018-003441-42
Status Completed
Phase Phase 3
First received
Last updated
Start date April 4, 2019
Est. completion date July 9, 2020

Study information

Verified date November 2021
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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)


Recruitment information / eligibility

Status Completed
Enrollment 504
Est. completion date July 9, 2020
Est. primary completion date July 9, 2020
Accepts healthy volunteers No
Gender All
Age group 40 Years to 150 Years
Eligibility Inclusion Criteria: - 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 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 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

Study Design


Related Conditions & MeSH terms

  • Heart Failure
  • Heart Failure With Preserved Ejection Fraction (HFpEF)

Intervention

Drug:
Dapagliflozin
Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.
Other:
Placebo
Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.

Locations

Country Name City State
Argentina Research Site Caba
Argentina Research Site Ciudad Autonoma de Buenos Aire
Argentina Research Site Ciudad Autonomade Buenos Aires
Brazil Research Site Blumenau
Brazil Research Site Brasillia
Brazil Research Site Porto Alegre
Brazil Research Site Sao Paulo
Brazil Research Site São Paulo
Bulgaria Research Site Plovdiv
Bulgaria Research Site Sofia
Bulgaria Research Site Sofia
Bulgaria Research Site Veliko Tarnovo
Canada Research Site Ajax Ontario
Canada Research Site Chicoutimi Quebec
Canada Research Site Edmonton Alberta
Canada Research Site Gatineau Quebec
Canada Research Site Guelph Ontario
Canada Research Site Longueuil Quebec
Canada Research Site Moncton New Brunswick
Canada Research Site Montreal Quebec
Canada Research Site Montreal Quebec
Canada Research Site Mount Pearl Newfoundland and Labrador
Canada Research Site North York Ontario
Canada Research Site Quebec
Canada Research Site Quebec
Canada Research Site Quebec
Canada Research Site Scarborough Ontario
Canada Research Site Scarborough Ontario
Canada Research Site St-Georges Quebec
Canada Research Site St. John's Newfoundland and Labrador
Denmark Research Site Århus N
Denmark Research Site Esbjerg
Denmark Research Site Hellerup
Denmark Research Site Hjørring
Denmark Research Site Hvidovre
Denmark Research Site København
Denmark Research Site Næstved
Denmark Research Site Odense C
Denmark Research Site Randers
Denmark Research Site Svendborg
Italy Research Site Bergamo
Italy Research Site Milano
Italy Research Site Napoli
Italy Research Site Palermo
Italy Research Site Roma
Italy Research Site San Giovanni Rotondo
Japan Research Site Akashi-shi
Japan Research Site Daito-shi
Japan Research Site Kasugai-shi
Japan Research Site Matsubara-shi
Japan Research Site Naha
Japan Research Site Omihachiman-shi
Japan Research Site Osaka-shi
Japan Research Site Shunan-shi
Japan Research Site Takarazuka-shi
Japan Research Site Toshima-ku
Korea, Republic of Research Site Gangwon-do
Korea, Republic of Research Site Gwangju
Korea, Republic of Research Site Seongnam-si
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Slovakia Research Site Brezno
Slovakia Research Site Lucenec
Slovakia Research Site Martin
Slovakia Research Site Presov
Slovakia Research Site Ruzomberok
South Africa Research Site Cape Town
South Africa Research Site Diepkloof, Soweto
South Africa Research Site Pinelands
Sweden Research Site Borås
Sweden Research Site Göteborg
Sweden Research Site Lund
Sweden Research Site Ostersund
Sweden Research Site Stockholm
Sweden Research Site Stockholm
Sweden Research Site Umeå
United States Research Site Abington Pennsylvania
United States Research Site Alexander City Alabama
United States Research Site Annapolis Maryland
United States Research Site Arlington Heights Illinois
United States Research Site Beverly Hills California
United States Research Site Bossier City Louisiana
United States Research Site Burlington North Carolina
United States Research Site Cincinnati Ohio
United States Research Site Doylestown Pennsylvania
United States Research Site Fort Payne Alabama
United States Research Site Hazel Crest Illinois
United States Research Site Jacksonville Florida
United States Research Site Louisville Kentucky
United States Research Site Miami Florida
United States Research Site Miami Florida
United States Research Site Munster Indiana
United States Research Site New Brunswick New Jersey
United States Research Site Pittsburgh Pennsylvania
United States Research Site Ridgewood New Jersey
United States Research Site Rosedale New York
United States Research Site Seattle Washington
United States Research Site Spring Texas
United States Research Site Torrance California
United States Research Site Tucker Georgia
United States Research Site Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Canada,  Denmark,  Italy,  Japan,  Korea, Republic of,  Slovakia,  South Africa,  Sweden, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. At baseline and at week 16 or death before week 16
Primary 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. At baseline and at week 16 or death before week 16
Primary 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. At baseline and at week 16 or death before week 16
Secondary 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. At baseline and at end of study or death before week 16.
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