Dapagliflozin With or Without Spironolactone for HFpEF

NCT05676684 | Completed Phase 2

• 1 other identifier: SOGALDI-PEF
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Blood levels of NT-pro BNP (Log transformed)

  Comparison of NT-pro BNP levels between groups

  Visit 1 Day 0 / Visit 2 Day 84 [Day 77 to Day 91] / Visit 3 Day 175 [Day 168 to Day 182]

Secondary Outcomes (13)

• Proportion of patients reaching a 20% or greater reduction in NT-proBNP levels

  Visit 1 Day 0 / Visit 2 Day 84 [Day 77 to Day 91] / Visit 3 Day 175 [Day 168 to Day 182]

• Circulating levels of PICP, PIIINP and CITP

  Visit 1 Day 0 / Visit 2 Day 84 [Day 77 to Day 91] / Visit 3 Day 175 [Day 168 to Day 182]

• Indexed Left Atrial Volume (LAVi)

  Visit 1 Day 0 / Visit 2 Day 84 [Day 77 to Day 91] / Visit 3 Day 175 [Day 168 to Day 182]

• Left Ventricular Ejection Fraction (LVEF)

  Visit 1 Day 0 / Visit 2 Day 84 [Day 77 to Day 91] / Visit 3 Day 175 [Day 168 to Day 182]

• Lateral E/e

  Visit 1 Day 0 / Visit 2 Day 84 [Day 77 to Day 91] / Visit 3 Day 175 [Day 168 to Day 182]

Study Arms (2)

[Dapagliflozin] - [Dapagliflozin + Spironolactone]

EXPERIMENTAL

Drug will be administered according to sequence: Dapagliflozin \[week 1-12\] - Dapagliflozin + Spironolactone \[week 13-25\]

Drug: Dapagliflozin; Drug: Spironolactone + Dapagliflozin

[Dapagliflozin + Spironolactone] - [Dapagliflozin]

EXPERIMENTAL

Drug will be administered according to sequence: Dapagliflozin + Spironolactone \[week 1-12\] - Dapagliflozin \[week 13-25\]

Drug: Dapagliflozin; Drug: Spironolactone + Dapagliflozin

Interventions

Dapagliflozin DRUG

A: Dapagliflozin 10 mg once daily

Also known as: Forxiga(R)

[Dapagliflozin + Spironolactone] - [Dapagliflozin]; [Dapagliflozin] - [Dapagliflozin + Spironolactone]

Spironolactone + Dapagliflozin 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)

Also known as: Forxiga(R) + Aldactone(R)

[Dapagliflozin + Spironolactone] - [Dapagliflozin]; [Dapagliflozin] - [Dapagliflozin + Spironolactone]

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Stable/chronic ambulatory patients i.e., patients without need for hospitalization within the last 30 days due to heart failure decompensation episodes

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
• Participation in another clinical study with an investigational product during the last month
• 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)
• Major surgical procedure, coronary, cerebral or peripheral vascular events or sepsis in the prior 90 days
• Cancer (life-limiting or less than 2 years in remission)
• Any previously confirmed autoimmune disease
• 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
• Previously confirmed cardiac amyloidosis
• Severe valvulopathy according to the echocardiogram report
• Patients with a known hypersensitivity or intolerance to spironolactone or dapagliflozin or any of the excipients of the products.
• Female patients currently pregnant (confirmed by a positive pregnancy test) or intent to become pregnant or breast feeding.

Sponsors & Collaborators

• Universidade do Porto: lead
• Centro Hospitalar De São João, E.P.E.: collaborator
• Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.: collaborator

Study Sites (2)

Unidade Local de Saúde Gaia/Espinho

Porto, Gaia, 4434-502, Portugal

Location

Centro Hospitalar Universitário São João

Porto, 4200-319, Portugal

Location

Related Publications (1)

• 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.

  PMID: 40738559 DERIVED

MeSH Terms

Interventions

dapagliflozin; Spironolactone

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Adelino Leite-Moreira, MD, PhD

  Universidade do Porto

  PRINCIPAL INVESTIGATOR

• Ricardo Fontes-Carvalho, MD, PhD

  Unidade Local de Saúde Gaia/Espinho

  PRINCIPAL INVESTIGATOR

• João Ferreira, MD, PhD

  Universidade do Porto

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomised, open-label, two-treatment, two-period, cross-over trial

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: January 9, 2023
• Study Start: September 15, 2022
• Primary Completion: November 29, 2024
• Study Completion: November 29, 2024
• Last Updated: August 17, 2025

Record last verified: 2025-03

Locations

PT (2)