Dapagliflozin With or Without Spironolactone for HFpEF

NCT ID: NCT05676684

Last Updated: 2025-08-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-15
• Study Completion Date: 2024-11-29

Brief Summary

Heart failure (HF) is a condition in which the heart does not contract ("pump") or relax well, leading to insufficient perfusion of vital organs. Ankle swelling, fatigue, and breathlessness are some of the features of this syndrome. There are different causes for HF (eg., infarct and hypertension) and two distinct types: HFrEF - HF with reduced ejection fraction - where the heart does not "pump" properly, and HFpEF - HF with preserved ejection fraction - the heart "pumps" but does not relax well. Treatment for HFrEF is better established than for HFpEF. In HFpEF, only mineralocorticoid receptors antagonists (MRAs) have been shown to reduce hospitalizations, circulating markers of cardiac dysfunction and fibrosis, and blood pressure. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a therapeutic class that reduces morbidity and mortality in patients with high cardiovascular risk and diabetes and in patients with HFrEF with and without diabetes. Trials are underway to test whether SGLT2i may also be useful for the treatment of HFpEF. This work aims to compare the effects of SGLT2i alone and in combination in an MRA in patients with HFpEF.

Conditions

Heart Failure With Preserved Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

[Dapagliflozin] - [Dapagliflozin + Spironolactone]

Drug will be administered according to sequence:

Dapagliflozin [week 1-12] - Dapagliflozin + Spironolactone [week 13-25]

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

A: Dapagliflozin 10 mg once daily

Spironolactone + Dapagliflozin

Intervention Type: DRUG

C: Dapagliflozin 10 mg once daily plus Spironolactone 25mg/every other day or 25mg/day (can be adjusted according to potassium and renal function)

[Dapagliflozin + Spironolactone] - [Dapagliflozin]

Drug will be administered according to sequence:

Dapagliflozin + Spironolactone [week 1-12] - Dapagliflozin [week 13-25]

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

A: Dapagliflozin 10 mg once daily

Spironolactone + Dapagliflozin

Intervention Type: DRUG

C: Dapagliflozin 10 mg once daily plus Spironolactone 25mg/every other day or 25mg/day (can be adjusted according to potassium and renal function)

Interventions

Dapagliflozin

A: Dapagliflozin 10 mg once daily

Intervention Type: DRUG

Spironolactone + Dapagliflozin

C: Dapagliflozin 10 mg once daily plus Spironolactone 25mg/every other day or 25mg/day (can be adjusted according to potassium and renal function)

Intervention Type: DRUG

Other Intervention Names

Forxiga(R); Forxiga(R) + Aldactone(R)

Eligibility Criteria

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures

2. HFpEF diagnosis* (irrespective of time since diagnosis)

3. Male or female patients, aged ≥50 years

4. NYHA Class II-IV

5. LVEF > 40%

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:

1. LAVI ≥29 ml/m2 (≥34 ml/m2 if AF)

2. Lateral E/e' ≥9

3. LVMI ≥115 g/m2 If male or ≥95 g/m2 if female

4. 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 two weeks 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:

1. Surgically sterilized (e.g. underwent hysterectomy, bilateral salpingectomy or bilateral oophorectomy)

2. Clinically diagnosed infertile

3. 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 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:

1. Abstinence of heterosexual intercourse (when this is in line with preferred and usual lifestyle of the subject)

2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)

3. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)

4. Intrauterine device

5. Intrauterine hormone-releasing system

6. Bilateral tubal occlusion

7. Vasectomized partner, who has received medical assessment of the surgical success, or clinically diagnosed infertile partner

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 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)

4. Major 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. 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

9. Previously confirmed cardiac amyloidosis

10. Severe valvulopathy according to the echocardiogram report

11. Patients with a known hypersensitivity or intolerance to spironolactone or dapagliflozin or any of the excipients of the products.

12. Female patients currently pregnant (confirmed by a positive pregnancy test) or intent to become pregnant or breast feeding.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centro Hospitalar De São João, E.P.E.

OTHER

Sponsor Role: collaborator

Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.

OTHER_GOV

Sponsor Role: collaborator

Universidade do Porto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adelino Leite-Moreira, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidade do Porto

Ricardo Fontes-Carvalho, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Unidade Local de Saúde Gaia/Espinho

João Ferreira, MD, PhD

Role: STUDY_DIRECTOR

Universidade do Porto

Locations

Unidade Local de Saúde Gaia/Espinho

Porto, Gaia, Portugal

Centro Hospitalar Universitário São João

Porto, , Portugal

Countries

Portugal

References

Ferreira JP, Vasques-Novoa F, Saraiva F, Oliveira AC, Almeida J, Batista AB, Barbosa A, Ferreira AF, Costa C, Diaz SO, Santos-Ferreira D, Frioes F, Goncalves C, Guimaraes JT, Leite M, Marques P, Mascarenhas J, Matos MI, Pereira C, Rodrigues P, Sharma A, Silva G, Pereira-Sousa I, Sousa C, Zannad F, Pimenta J, Fontes-Carvalho R, Leite-Moreira A. Sodium-Glucose Cotransporter 2 Inhibitor With and Without an Aldosterone Antagonist for Heart Failure With Preserved Ejection Fraction: The SOGALDI-PEF Trial. J Am Coll Cardiol. 2025 Aug 5;86(5):320-333. doi: 10.1016/j.jacc.2025.05.033.

Reference Type: DERIVED

PMID: 40738559 (View on PubMed)

Other Identifiers

SOGALDI-PEF

Identifier Type: -

Identifier Source: org_study_id