Dapagliflozin With or Without Spironolactone for HFpEF

Prior treatment

• Participation in another clinical study with an investigational product during the last month
• Major surgical procedure, coronary, cerebral or peripheral vascular events or sepsis in the prior 90 days
• Any previously confirmed autoimmune disease
• Previously confirmed cardiac amyloidosis

Other illness

• Cancer (life-limiting or less than 2 years in remission)
• Type 1 Diabetes
• Ability to walk is, in the investigator's opinion, clearly limited by joint disease or other locomotor problems or lung diseases rather than by cardiorespiratory fitness
• Patients with a known hypersensitivity or intolerance to spironolactone or dapagliflozin or any of the excipients of the products.

Other

• Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
• Unwilling to sign the informed consent form (if the patient wants to participate but cannot sign for any reason, then a third-person testimony may sign/complete informed consent form on patient's behalf)
• Severe valvulopathy according to the echocardiogram report
• Female patients currently pregnant (confirmed by a positive pregnancy test) or intent to become pregnant or breast feeding.

• Provision of informed consent prior to any study specific procedures
• HFpEF diagnosis\* (irrespective of time since diagnosis)
• Male or female patients, aged ≥50 years
• NYHA Class II-IV
• LVEF \> 40%
• NT-pro BNP ≥220 pg/mL or BNP ≥80 pg/mL if in sinus rhythm (SR)
• NT-pro BNP ≥660 pg/mL or BNP ≥240 pg/mL if in atrial fibrillation (AF)
• Echocardiography with at least one of the following criteria:
  • LAVI ≥29 ml/m2 (≥34 ml/m2 if AF)
  • Lateral E/e' ≥9
  • LVMI ≥115 g/m2 If male or ≥95 g/m2 if female
  • LV wall thickness ≥12mm
• eGFR ≥30 ml/min/1.73m2 (CKD-EPI formula)
• Blood Potassium ≤5.5 mmol/L
• Not treated with MRAs and/or SGLT2i within the previous two weeks before inclusion and have no history of diabetic ketoacidosis while in treatment with SGLT2 inhibitors
• Stable/chronic ambulatory patients i.e., patients without need for hospitalization within the last 30 days due to heart failure decompensation episodes
• If female, she must be a woman of non-childbearing potential. That is, she must be:
  • Surgically sterilized (e.g. underwent hysterectomy, bilateral salpingectomy or bilateral oophorectomy)
  • Clinically diagnosed infertile
  • In a post-menopausal state, defined as no menses for 12 months without an alternative medical cause.
• A female patient of childbearing potential must have a negative serum pregnancy test at Visit 1 (Day 0) and must agree to use consistently and correctly (from 28 days prior to first study treatment administration until at least 7 days after last study treatment administration) one of the following highly effective methods of contraception:
  • Abstinence of heterosexual intercourse (when this is in line with preferred and usual lifestyle of the subject)
  • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  • Intrauterine device
  • Intrauterine hormone-releasing system
  • Bilateral tubal occlusion
  • Vasectomized partner, who has received medical assessment of the surgical success, or clinically diagnosed infertile partner