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SOGALDI-PEF: Dapagliflozin, Spironolactone or Both for HFpEF

Sponsor
Universidade do Porto (Other)
Overall Status
Recruiting
CT.gov ID
NCT05676684
Collaborator
FMUP (Other), Centro Hospitalar Universitário de São João, E.P.E. (Other), Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E. (Other)
108
Enrollment
2
Locations
6
Arms
27
Anticipated Duration (Months)
54
Patients Per Site
2
Patients Per Site Per Month

Study Details

Study Description

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 MRAs and SGLT2i alone, plus their combination in patients with HFpEF.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
108 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Prospective, randomised, open-label, three-treatment, three-period, cross-over trial with a factorial designProspective, randomised, open-label, three-treatment, three-period, cross-over trial with a factorial design
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Sep 15, 2022
Anticipated Primary Completion Date :
Sep 15, 2024
Anticipated Study Completion Date :
Dec 15, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: [Dapagliflozin] - [Spironolactone] - [Dapagliflozin + Spironolactone]

Drug will be administered according to sequence: Dapagliflozin [week 1-12] - Spironolactone [week 17-28] - Dapagliflozin + Spironolactone [week 33-44]

Drug: Dapagliflozin
A: Dapagliflozin 10 mg once daily
Other Names:
  • Forxiga(R)

    • Drug: Spironolactone
    B: Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Aldactone(R)

    • Drug: Spironolactone + Dapagliflozin
    C: Dapagliflozin 10 mg once daily plus Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Forxiga(R) + Aldactone(R)

    		•
    Experimental: [Dapagliflozin] - [Dapagliflozin + Spironolactone] - [Spironolactone]

    Drug will be administered according to sequence: Dapagliflozin [week 1-12] - Dapagliflozin + Spironolactone [week 17-28] - Spironolactone [week 33-44]

    Drug: Dapagliflozin
    A: Dapagliflozin 10 mg once daily
    Other Names:
  • Forxiga(R)

    • Drug: Spironolactone
    B: Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Aldactone(R)

    • Drug: Spironolactone + Dapagliflozin
    C: Dapagliflozin 10 mg once daily plus Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Forxiga(R) + Aldactone(R)

    		•
    Experimental: [Spironolactone] - [Dapagliflozin] - [Dapagliflozin + Spironolactone]

    Drug will be administered according to sequence: Spironolactone [week 1-12] - Dapagliflozin [week 17-28] - Dapagliflozin + Spironolactone [week 33-44]

    Drug: Dapagliflozin
    A: Dapagliflozin 10 mg once daily
    Other Names:
  • Forxiga(R)

    • Drug: Spironolactone
    B: Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Aldactone(R)

    • Drug: Spironolactone + Dapagliflozin
    C: Dapagliflozin 10 mg once daily plus Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Forxiga(R) + Aldactone(R)

    		•
    Experimental: [Spironolactone] - [Dapagliflozin + Spironolactone] - [Dapagliflozin]

    Drug will be administered according to sequence: Spironolactone [week 1-12] - Dapagliflozin + Spironolactone [week 17-28] - Dapagliflozin [week 33-44]

    Drug: Dapagliflozin
    A: Dapagliflozin 10 mg once daily
    Other Names:
  • Forxiga(R)

    • Drug: Spironolactone
    B: Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Aldactone(R)

    • Drug: Spironolactone + Dapagliflozin
    C: Dapagliflozin 10 mg once daily plus Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Forxiga(R) + Aldactone(R)

    		•
    Experimental: [Dapagliflozin + Spironolactone] - [Spironolactone] - [Dapagliflozin]

    Drug will be administered according to sequence: Dapagliflozin + Spironolactone [week 1-12] - Spironolactone [week 17-28] - Dapagliflozin [week 33-44]

    Drug: Dapagliflozin
    A: Dapagliflozin 10 mg once daily
    Other Names:
  • Forxiga(R)

    • Drug: Spironolactone
    B: Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Aldactone(R)

    • Drug: Spironolactone + Dapagliflozin
    C: Dapagliflozin 10 mg once daily plus Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Forxiga(R) + Aldactone(R)

    		•
    Experimental: [Dapagliflozin + Spironolactone] - [Dapagliflozin] - [Spironolactone]

    Drug will be administered according to sequence: Dapagliflozin + Spironolactone [week 1-12] - Dapagliflozin [week 17-28] - Spironolactone [week 33-44]

    Drug: Dapagliflozin
    A: Dapagliflozin 10 mg once daily
    Other Names:
  • Forxiga(R)

    • Drug: Spironolactone
    B: Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Aldactone(R)

    • Drug: Spironolactone + Dapagliflozin
    C: Dapagliflozin 10 mg once daily plus Spironolactone 25 mg once daily (can be adjusted according to potassium and renal function)
    Other Names:
  • Forxiga(R) + Aldactone(R)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Blood levels of NT-pro BNP (Log transformed) [month 3, month 7, month 11]

      Comparison of NT-pro BNP levels between groups

    Secondary Outcome Measures

    1. Proportion of patients reaching a 20% or greater reduction in NT-proBNP levels [month 3, month 7, month 11]

      Measured in blood samples

    2. Circulating levels of PICP, PIIINP and CITP [month 3, month 7, month 11]

      Measured in blood samples the circulating levels of procollagen type I carboxy-terminal propeptide (PICP), N-terminal propeptide of procollagen type III (PIIINP), C-terminal telopeptide of collagen type I (CITP)

    3. Indexed Left Atrial Volume (LAVi) [month 3, month 7, month 11]

      Transthoracic echocardiogram

    4. Left Ventricular Ejection Fraction (LVEF) [month 3, month 7, month 11]

      Transthoracic echocardiogram

    5. Lateral E/e [month 3, month 7, month 11]

      Transthoracic echocardiogram

    6. Indexed Left Ventricular Mass (LVMi) [month 3, month 7, month 11]

      Transthoracic echocardiogram

    7. Pulmonary Artery Systolic Pressure (PASP) [month 3, month 7, month 11]

      Transthoracic echocardiogram

    8. Systolic and Diastolic Blood Pressure (SBP/DBP) [month 3, month 7, month 11]

      Measure in the clinical appointment after 5min of seated rest. Mean of 3 automatic oscillometric measurements

    9. Estimated glomerular filtration rate (eGFR) [month 3, month 7, month 11]

      Calculated from the serum creatinine using the 2021 CKD-EPI creatinine-based formula

    10. Microalbuminuria (log-transformed) [month 3, month 7, month 11]

      Spot urine

    11. Urinary sodium/natriuresis [month 3, month 7, month 11]

      Spot urine

    12. Serum potassium (K+) [month 3, month 7, month 11]

      Concentration of potassium in the blood

    13. Health-related quality of life (HR-QoL) [month 3, month 7, month 11]

      HR-QoL assessed by the Kansas City Cardiomyopathy Questionnaire a 23-item instrument. All items are measured on a Likert scale with 5-7 response options. KCCQ scores are scaled from 0 to 100 and summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Provision of informed consent prior to any study specific procedures

    • HFpEF diagnosis* (irrespective of time from diagnosis)

    • Male or female patients, aged ≥50 years

    • NYHA Class II-IV

    • LVEF ≥45%

    • 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 month 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 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:

    • 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

    Exclusion Criteria:

    • 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 or unable to sign the informed consent form

    • 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

    • Severe hepatic impairment (Child-Pugh class C)

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Centro Hospitalar Universitário São João Porto Portugal 4200-319
    2 Centro Hospitalar Vila Nova de Gaia/Espinho Porto Portugal 4434-502

    Sponsors and Collaborators

    • Universidade do Porto
    • FMUP
    • Centro Hospitalar Universitário de São João, E.P.E.
    • Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.

    Investigators

    • Study Director: Adelino Leite-Moreira, MD, PhD, Universidade do Porto

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Universidade do Porto
    ClinicalTrials.gov Identifier:
    NCT05676684
    Other Study ID Numbers:
    • SOGALDI-PEF
    First Posted:
    Jan 9, 2023
    Last Update Posted:
    Jan 13, 2023
    Last Verified:
    Sep 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:
    Heart Failure
    Dapagliflozin
    Spironolactone

    Study Results

    No Results Posted as of Jan 13, 2023