Clinical trial NCT05770167: Effects of Dapagliflozin on Cardiorespiratory Parameters in Heart Failure
Official title: Effects of Dapagliflozin on Exercise Capacity, Respiratory Function, Biomarkers, Sleep Apnoeas and Left Ventricular Remodelling in Heart Failure Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Heart Failure
Heart Failure With Reduced Ejection Fraction
Left Ventricle Remodeling
Sleep Apnea
Cardiopulmonary Exercise Test
Lead sponsor: Centro Cardiologico Monzino
Sponsor class: OTHER
First posted: 2023-03-15
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: exercise capacity change
timeFrame: 6 months
Secondary outcomes:
measure: change in FEV1
timeFrame: 6 months
measure: change in DLCO
timeFrame: 6 months
measure: Change in Nt-proBNP
timeFrame: 6 months
measure: Change in ST-2
timeFrame: 6 months
measure: Change in surfactant binding protein
timeFrame: 6 months
measure: change in LVEF
timeFrame: 6 months
measure: change in left ventricular volumes
timeFrame: 6 months
measure: change in central sleep apnoeas
timeFrame: 6 months
measure: change in quality of life
timeFrame: 6 months
measure: change in hydration index
timeFrame: 6 months
measure: population stratification according to VO2 peak higher and lower than 15 ml/min/kg
timeFrame: 6 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Centro Cardiologico Monzino
Study officials:
affiliation: Centro Cardiologico Monzino
name: Massimo Mapelli, MD
role: PRINCIPAL_INVESTIGATOR
References: