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
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 Reduced Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure With Reduced Ejection Fraction (HFrEF)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-03-15
Enrollment: 313
Sex: ALL
Minimum age (years): 18
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 Reduced Ejection Fraction (HFrEF)


Eligibility criteria: 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

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 prior to 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: Fairhope
country: United States
facility: Research Site
state: Alabama
city: Fort Payne
country: United States
facility: Research Site
state: Alabama
city: Mobile
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: Stamford
country: United States
facility: Research Site
state: Connecticut
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Tucker
country: United States
facility: Research Site
state: Georgia
city: Munster
country: United States
facility: Research Site
state: Indiana
city: Petoskey
country: United States
facility: Research Site
state: Michigan
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: New Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Rosedale
country: United States
facility: Research Site
state: New York
city: Burlington
country: United States
facility: Research Site
state: North Carolina
city: Abington
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Tullahoma
country: United States
facility: Research Site
state: Tennessee
city: Falls Church
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Blumenau
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: Moncton
country: Canada
facility: Research Site
state: New Brunswick
city: St. John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Ajax
country: Canada
facility: Research Site
state: Ontario
city: North York
country: Canada
facility: Research Site
state: Ontario
city: Oshawa
country: Canada
facility: Research Site
state: Ontario
city: Scarborough
country: Canada
facility: Research Site
state: Ontario
city: Stoney Creek
country: Canada
facility: Research Site
state: Ontario
city: York
country: Canada
facility: Research Site
state: Ontario
city: Gatineau
country: Canada
facility: Research Site
state: Quebec
city: Longueuil
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: St-Georges
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Quebec
country: Canada
facility: Research Site
city: Quebec
country: Canada
facility: Research Site
city: Esbjerg
country: Denmark
facility: Research Site
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
facility: Research Site
city: Århus N
country: Denmark
facility: Research Site
city: Daito-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Matsubara-shi
country: Japan
facility: Research Site
city: Naha
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Sayama-shi,
country: Japan
facility: Research Site
city: Shunan-shi
country: Japan
facility: Research Site
city: Takarazuka-shi
country: Japan
facility: Research Site
city: Gangwon-do
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: Lucenec
country: Slovakia
facility: Research Site
city: Martin
country: Slovakia
facility: Research Site
city: Presov
country: Slovakia
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Diepkloof, Soweto
country: South Africa
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: