SOdium-Glucose cotransporter 2 inhibitor, ALDosterone AntagonIst, or both for heart failure with Preserved Ejection Fraction: a two-centre randomised three-treatment three-period crossover trial

Phase 1

• Conditions: Heart Failure with Preserved Ejection Fraction; MedDRA version: 20.1Level: LLTClassification code 10076396Term: Heart failure with preserved ejection fractionSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2020-000973-26-PT
• Lead Sponsor: Faculdade de Medicina da Universidade do Porto

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-02-02
• Last Update Posted: 16 October 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 108

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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified