Clinical trial NCT03877224: DETERMINE-preserved - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Preserved Ejection Fraction
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-03-15
Enrollment: 504
Sex: ALL
Minimum age (years): 40
Maximum age (years): 150
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)


Eligibility criteria: 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

Primary outcomes:
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)
timeFrame: At baseline and at week 16 or death before week 16
measure: 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)
timeFrame: At baseline and at week 16 or death before week 16
measure: Change From Baseline in 6-minute Walk Distance (6MWD) at Week 16 (Larger Distances Represent Better Functional Capacity)
timeFrame: At baseline and at week 16 or death before week 16
Secondary outcomes:
measure: 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).
timeFrame: At baseline and at end of study or death before week 16.
Other outcomes:
Locations:
city: Alexander City
country: United States
facility: Research Site
state: Alabama
city: Fort Payne
country: United States
facility: Research Site
state: Alabama
city: Beverly Hills
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: Tucker
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state: Georgia
city: Arlington Heights
country: United States
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state: Illinois
city: Hazel Crest
country: United States
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state: Illinois
city: Munster
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state: Indiana
city: Louisville
country: United States
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state: Kentucky
city: Bossier City
country: United States
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state: Louisiana
city: Annapolis
country: United States
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state: Maryland
city: New Brunswick
country: United States
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state: New Jersey
city: Ridgewood
country: United States
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state: New Jersey
city: Rosedale
country: United States
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state: New York
city: Burlington
country: United States
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state: North Carolina
city: Winston-Salem
country: United States
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state: North Carolina
city: Cincinnati
country: United States
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state: Ohio
city: Abington
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state: Pennsylvania
city: Doylestown
country: United States
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state: Pennsylvania
city: Pittsburgh
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state: Pennsylvania
city: Spring
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state: Texas
city: Seattle
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state: Washington
city: Caba
country: Argentina
facility: Research Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Research Site
city: Ciudad Autonomade Buenos Aires
country: Argentina
facility: Research Site
city: Blumenau
country: Brazil
facility: Research Site
city: Brasillia
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Sao Paulo
country: Brazil
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city: São Paulo
country: Brazil
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city: Plovdiv
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Veliko Tarnovo
country: Bulgaria
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Moncton
country: Canada
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state: New Brunswick
city: Mount Pearl
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Ajax
country: Canada
facility: Research Site
state: Ontario
city: Guelph
country: Canada
facility: Research Site
state: Ontario
city: North York
country: Canada
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state: Ontario
city: Scarborough
country: Canada
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state: Ontario
city: Scarborough
country: Canada
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state: Ontario
city: Chicoutimi
country: Canada
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state: Quebec
city: Gatineau
country: Canada
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state: Quebec
city: Longueuil
country: Canada
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state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
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state: Quebec
city: St-Georges
country: Canada
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state: Quebec
city: Quebec
country: Canada
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city: Quebec
country: Canada
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city: Quebec
country: Canada
facility: Research Site
city: Esbjerg
country: Denmark
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city: Hellerup
country: Denmark
facility: Research Site
city: Hjørring
country: Denmark
facility: Research Site
city: Hvidovre
country: Denmark
facility: Research Site
city: København
country: Denmark
facility: Research Site
city: Næstved
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Randers
country: Denmark
facility: Research Site
city: Svendborg
country: Denmark
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city: Århus N
country: Denmark
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city: Bergamo
country: Italy
facility: Research Site
city: Milano
country: Italy
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city: Napoli
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: San Giovanni Rotondo
country: Italy
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city: Akashi-shi
country: Japan
facility: Research Site
city: Daito-shi
country: Japan
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city: Kasugai-shi
country: Japan
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city: Matsubara-shi
country: Japan
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city: Naha
country: Japan
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city: Omihachiman-shi
country: Japan
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city: Osaka-shi
country: Japan
facility: Research Site
city: Shunan-shi
country: Japan
facility: Research Site
city: Takarazuka-shi
country: Japan
facility: Research Site
city: Toshima-ku
country: Japan
facility: Research Site
city: Gangwon-do
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Brezno
country: Slovakia
facility: Research Site
city: Lucenec
country: Slovakia
facility: Research Site
city: Martin
country: Slovakia
facility: Research Site
city: Presov
country: Slovakia
facility: Research Site
city: Ruzomberok
country: Slovakia
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Diepkloof, Soweto
country: South Africa
facility: Research Site
city: Pinelands
country: South Africa
facility: Research Site
city: Borås
country: Sweden
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Ostersund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Umeå
country: Sweden
facility: Research Site
Study officials:
References: