Effects of Dapagliflozin on Cardiorespiratory Parameters in Heart Failure

NCT05770167 | Unknown

• 1 other identifier: CCM 1756
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Dapagliflozin is a molecule belonging to the class of sodium-glucose transporter type 2 (SGLT2-i) inhibitors. This type of drug, initially used in the treatment of diabetes mellitus, has in recent years demonstrated significant prognostic benefit in patients with heart failure even in the absence of diabetes mellitus. The new international heart failure guidelines have taken up this evidence by suggesting the use of SGLT2-i therapy in patients with heart failure with reduced ejection fraction (HFrEF). Given the drug's recent introduction into clinical routine, the evaluation of "field" experience is important to refine the clinical management of patients treated with SGLT2-i. Moreover, SGLT2-i has currently been shown to be effective in some small preliminary studies in improving ejection fraction and some echocardiographic parameters of ventricular remodelling on top of concomitant optimal medical therapy, although further data are needed in this regard. In particular, the potential benefit of SGLT2-i therapy on exercise capacity, respiratory function parameters, biomarkers and left ventricular remodelling in patients with heart failure has not been extensively studied at present. In this regard, the cardiopulmonary exercise test (CPET) allows the derivation of prognostic functional parameters in patients with chronic heart failure such as peak VO2 and the ventilation/CO2 slope. CPET is a valid, recognised and accurate tool for risk stratification in patients with heart failure. In addition, there are no data available on the effect of SGLT2-i on lung diffusion (DLCO) and specific markers of the alveolar-capillary membrane, such as surfactant binding proteins, as well as on the presence of sleep apnoea, a particularly relevant parameter for the prognosis of decompensated patients. The aim of the study is to evaluate changes in exercise capacity, spirometry, DLCO, echocardiographic parameters of left ventricular systolic-diastolic function, Nt-proBNP dosage, ST-2, surfactant binding proteins, sleep apnoea, impedance measurement and quality of life in a single-centre cohort of 70 patients with heart failure with stable reduced left ventricular ejection fraction (functional class NYHA II and III) and guideline candidates for treatment with Dapagliflozin. Patients will undergo, as per regular clinical practice, an initial assessment (baseline) that will include a clinical evaluation, KCCQ questionnaire for quality of life assessment, spirometry, DLCO, impedance measurement, polysomnography, a cardiopulmonary ramp test, blood tests with dosage of Nt-proBNP, ST-2 and surfactant binding protein, and a standard transthoracic echocardiogram. At baseline, the patient will start treatment with Dapagliflozin at the standard dosage of 10mg/day. A similar evaluation with the same study procedures will be performed 6 months after the start of therapy. A re-evaluation of the patient including venous blood sampling is planned between 2 and 4 weeks after the start of Dapagliflozin from clinical practice. In the context of this sampling, the assay of the biomarkers under study will also be repeated.

Conditions

Heart Failure; Heart Failure With Reduced Ejection Fraction; Left Ventricle Remodeling; Sleep Apnea; Cardiopulmonary Exercise Test

Outcome Measures

Primary Outcomes (1)

• exercise capacity change

  Evaluation of the change in patients' exercise capacity by raising oxygen consumption at peak exercise during cardiopulmonary testing

  6 months

Secondary Outcomes (11)

• change in FEV1

  6 months

• change in DLCO

  6 months

• Change in Nt-proBNP

  6 months

• Change in ST-2

  6 months

• Change in surfactant binding protein

  6 months

Eligibility Criteria

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

Study Population

patients with heart failure with reduced left ventricular ejection fraction, stable (NYHA functional class II and III) and guideline candidates for treatment with Dapagliflozin

You may qualify if:

• Age \>18 years
• stable clinical conditions
• Diagnosis of heart failure according to European guidelines (ESC) with EF≤40%
• New York Heart Association Class (NYHA) II-III, despite optimised treatment for heart failure, candidates for treatment with Dapagliflozin according to current guidelines
• Ability to perform cardiopulmonary testing (CPET)
• Patients who have signed written informed consent

You may not qualify if:

• Contraindication for Dapaglilozin prescription
• Moderate-severe obstructive pulmonary disease (COPD)
• Estimated glomerular filtrate (eGFR) \<30 mL/min/1.73m2 according to MDRD criteria
• Inability or contraindication to perform a CPET
• Taking an investigational drug within 30 days prior to administration of Dapagliflozin

Sponsors & Collaborators

• Centro Cardiologico Monzino: lead

Study Sites (1)

Centro Cardiologico Monzino

Milan, 20138, Italy

RECRUITING

MeSH Terms

Conditions

Heart Failure; Ventricular Remodeling; Sleep Apnea Syndromes

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Massimo Mapelli, MD

  Centro Cardiologico Monzino

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massimo Mapelli, MD

CONTACT

+39 0258002930; massimo.mapelli@ccfm.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2023
• First Posted: March 15, 2023
• Study Start: May 6, 2022
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: March 15, 2023

Record last verified: 2023-02

Locations

IT (1)