Heart Failure with Preserved Ejection Fraction (HFpEF)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed informed consent prior to any study specific procedures. 2. Male or female patients age =40 years. 3. Documented diagnosis of symptomatic heart failure (NYHA class II-IV) at enrolment, and a medical history of typical symptoms/signs of heart failure =6 weeks before enrolment with at least intermittent need for diuretic treatment. 4. Left Ventricular Ejection Fraction (LVEF) >40% and evidence of structural heart disease (i.e. left ventricular hypertrophy or left atrial enlargement ) documented by the most recent echocardiogram, and/or cardiac MR within the last 12 months prior to enrolment. For patients with prior acute cardiac events or procedures that may reduce LVEF, e.g. as defined in exclusion criterion 6, qualifying cardiac imaging assessment at least 12 weeks following the procedure/event is required. 5. NT-pro BNP =300 pg/ml at Visit 1 for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at Visit 1, NT-pro BNP must be =600 pg/mL. 6. Patients may be ambulatory, or hospitalized; patients must be off intravenous heart failure therapy (including diuretics) for at least 12 hours prior to enrolment and 24 hours prior to randomisation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3050 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3050
Exclusion criteria
Exclusion criteria: 1. Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to randomisation or previous intolerance to an SGLT2 inhibitor 2. Type 1 diabetes mellitus (T1D) 3. eGFR 50 kg/m2 11. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD (i.e., requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalisation for exacerbation of COPD requiring ventilatory assist within 12 months prior to enrolment) 12. Previous cardiac transplantation, or complex congenital heart disease. Planned cardiac resynchronisation therapy. 13. HF due to any of the following: known infiltrative cardiomyopathy (e.g. amyloid, sarcoid, lymphoma, endomyocardial fibrosis), active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), or uncorrected primary valvular disease 14. A life expectancy of less than 2 years due to any non-cardiovascular condition, based on investigator's clinical judgement. 15. Inability of the patient, in the opinion of the investigator, to understand and/or comply with study medications, procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study 16. Active malignancy requiring treatment (with the exception of basal cell or squamous cell carcinomas of the skin). 17. Acute or chronic liver disease with severe impairment of liver function (e.g., ascites, oesophageal varices, coagulopathy) 18. Women of child-bearing potential (i.e. those who are not chemically or surgically sterilised or post-menopausal) not willing to use a medically accepted method of contraception considered reliable in the judgment of the investigator OR who have a positive pregnancy test at randomisation OR who are breast-feeding 19. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca personnel and/or personnel at the study site) 20. Previous randomisation in the present study 21. Participation in another clinical study with an IP or device during the last month prior to enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether dapagliflozin is superior to placebo, when added to standard of care, in reducing the composite of CV death and HF events (hospitalisation for HF or urgent HF visit) in patients with HF and preserved systolic function.;Secondary Objective: To determine whether dapagliflozin is superior to placebo in reducing the total number of recurrent HF hospitalisations and CV death. To determine whether dapagliflozin is superior to placebo in improving Patient Reported Outcomes measured by KCCQ. To determine whether dapagliflozin is superior to placebo in reducing the proportion of patients with worsened NYHA class. To determine whether dapagliflozin is superior to placebo in reducing all-cause mortality.;Primary end point(s): Time to the first occurrence of any of the components of this composite: 1.CV death 2.Hospitalisation for HF 3.Urgent HF visit (e.g., emergency department or outpatient visit);Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated up to approximately 33 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Total number of (first and recurrent) hospitalisations for HF and CV death. Change from baseline in the total symptom score (TSS) of the KCCQ at 8 months. Proportion of patients with worsened NYHA class from baseline to 8 months. Time to the occurrence of death from any cause.;Timepoint(s) of evaluation of this end point: Total number of hospitalizations for HF and CV Death, and time to death from any cause are predicted to be evaluated up to 33 months from randomization (the study is event driven). The KCCQ and the NYHA class endpoints will be evaulated at 8 months after randomization. | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Hungary, Japan, Mexico, Netherlands, Peru, Poland, Romania, Russian Federation, Saudi Arabia, Spain, Taiwan, United States, Vietnam
Outcome results
None listed