Heart Failure with Preserved Ejection Fraction MedDRA version: 20.1 Level: LLT Classification code 10076396 Term: Heart failure with preserved ejection fraction System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Forxiga 10 mg comprimidos revestidos por película
Product Name: Not applicable
Product Code: Not applicable
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dapagliflozin
CAS N
Sponsors
Faculdade de Medicina da Universidade do Porto
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. HFpEF diagnosis (irrespective of time from diagnosis) 3. Male or female patients, aged =50 years 4. NYHA Class II-IV 5. LVEF =45% 6. NT-pro BNP =220 pg/mL or BNP =80 pg/mL if in sinus rhythm (SR) 7. NT-pro BNP =660 pg/mL or BNP =240 pg/mL if in atrial fibrillation (AF) 8. Echocardiography with at least one of the following criteria: a. LAVI =29 ml/m2 (=34 ml/m2 if AF) b. Lateral E/e` =9 c. LVMI =115 g/m2 If male or =95 g/m2 if female d. LV wall thickness =12mm 9. eGFR =30 ml/min/1.73m2 (CKD-EPI formula) 10. Blood Potassium =5.5 mmol/L 11. Not treated with MRAs and/or SGLT2i within the previous month before inclusion and have no history of diabetic ketoacidosis while in treatment with SGLT2 inhibitors 12. Stable/chronic ambulatory patients i.e., patients without need for hospitalization within the last 30 days due to heart failure decompensation episodes 13. If female, she must be a woman of non-childbearing potential. That is, she must be: a. Surgically sterilized (e.g. underwent hysterectomy, bilateral salpingectomy or bilateral oophorectomy) b. Clinically diagnosed infertile c. In a post-menopausal state, defined as no menses for 12 months without an alternative medical cause. 14. A female patient of childbearing potential must have a negative serum pregnancy test at Visit 1 (Day 0) and must agree to consistently and correctly use (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: a. Abstinence of heterosexual intercourse (when this is in line with preferred and usual lifestyle of the subject) b. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) c. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) d. Intrauterine device e. Intrauterine hormone-releasing system f. Bilateral tubal occlusion g. Vasectomized partner, who has received medical assessment of the surgical success, or clinically diagnosed infertile partner 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 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: 1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) 2. Participation in another clinical study with an investigational product during the last month 3. Unwilling or unable to sign the informed consent form 4. Surgical procedure, coronary, cerebral or peripheral vascular events or sepsis in the prior 90 days 5. Cancer (life-limiting or less than 2 years in remission) 6. Any previously confirmed autoimmune disease 7. Type 1 Diabetes 8. Severe hepatic impairment (Child-Pugh class C) 9. 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 10. Previously confirmed cardiac amyloidosis 11. Severe valvulopathy according to the echocardiogram report 12. Patients with a known hypersensitivity or intolerance to spironolactone or dapagliflozin or any of the excipients of the products. 13. Female patients currently pregnant (confirmed by a positive pregnancy test) or intent to become pregnant or breast feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of the spironolactone-dapagliflozin combination vs. spironolactone alone on the percentage change of the circulating levels of log-transformed NT-pro BNP relative to the baseline log NT-pro BNP levels.;Secondary Objective: - To assess the effect of the spironolactone-dapagliflozin combination vs. dapagliflozin alone on the percentage change of the circulating levels of log-transformed NT-pro BNP relative to the baseline log NT-pro BNP level. - To assess the effect of the spironolactone-dapagliflozin combination vs. spironolactone and dapagliflozin alone periods on the proportion of patients reaching 20% or greater reduction in NT-pro BNP levels - To compare the change in left atrial volume and blood pressure between the spironolactone-dapagliflozin combination period vs. spironolactone and dapagliflozin alone periods - To compare the change in quality-of-life score - To compare the effect of spironolactone, dapagliflozin, and spironolactone-dapagliflozin combination on the change of exercise tolerance, endothelial function, vascular structure, systemic congestion, natriuresis, glycosuria and microalbuminuria.;Primary end point(s): Log-transformed NT-pro BNP;Timepoint(s) of evaluation of this end point: During the entire study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Log-transformed NT-pro BNP • LAVi • Blood pressure • KCCQ score • Visual analogic symptom scale • VO2max • Pulse-wave velocity • Peripheral arterial tonometry (PAT) and reactive hyperaemia index • Pulmonary congestion evaluated by lung ultrasonography; • Bioelectrical impedance analysis • Glucose (urine) • Urinary sodium/natriuresis (urine); • Microalbuminuria (urine);;Timepoint(s) of evaluation of this end point: During the entire study | — |
Countries
Portugal
Contacts
Public ContactBlueClinical, Lda.
BlueClinical – Investigação e Desenvolvimento em Saúde, Lda
Outcome results
None listed