Effects of combined diuretic therapy on exercise capacity, alveolus-capillary diffusion, and maintenance of euvolemia in chronic congestive heart failure, diuretic therapy compared between loop diuretics and potassium sparing diuretics

INTERVENTION: Trade Name: DIAMO X‐ 250 MG COMPRESSE 12 COMPRESSE Product Name: DIAMOX Product Code: [DIAMOX] Pharmaceutical Form: Tablet INN or Proposed INN: ACETAZOLAMIDE CAS Number: 59‐66‐5 Current Sponsor code: NA Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Trade Name: ZAROXOLYN ‐ 10 MG COMPRESSE 50 COMPRESSE Pharmaceutical Form: Tablet INN or Proposed INN: METOLAZONE CAS Number: 17560‐51‐9 Current Sponsor code: NA Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Trade Name: ZAROXOLYN ‐ 5 MG COMPRESSE 50 COMPRESSE Pharmaceutical Form: Tablet INN or Proposed INN: METOLAZONE CAS Number: 17560‐51‐9 Current Sponsor code: NA Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ CONDITION: congestive heart failure ; MedDRA version: 20.0 Level: SOC Classification code 10007541 Term: Cardiac disorders System Organ Class: 10007541 ‐ Cardiac disorders Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] PRIMARY OUTCOME: Main Objective: To compare two different treatment strategies (control arm treated with loop diuretic and potassium sparing and experimental arm that will combine such therapy with acetazolamide and free‐dose metolazone) in patients with chronic heart failure. Specifically, the following will be assessed: trend of short‐ to medium‐term re‐hospitalizations, degree of congestion and volemia by body weight assessment and vector impedance measurement (BIVA), functional capacity by cardiopulmonary exercise testing (CPET), subjective perception of health status assessed by questionnaires, and neurohormonal response. Primary end point(s): Evaluate differences in the trend of short‐ to medium‐term re‐hospitalizations between chronic heart failure patients treated with standard diuretic therapy (control arm) and combination diuretic therapy (experimental arm) Secondary Objective: • Assess the degree of congestion and volemia through the course of body weight and measurement of vector impedance (BIVA) between patients with chronic heart failure treated with standard diuretic therapy and combined diuretic therapy; • To evaluate differences in the effects on functional capacity through CPET with VO2 max measurement and on alveolar‐capillary diffusion between patients with chronic heart failure treated with standard diuretic therapy and combined diuretic therapy; • Assess differences in the trend of subjective perception of health through Kansas City Cardiomiopathy Questioning between patients with chronic heart failure treated with standard diuretic therapy and combined diuretic therapy; • Assess differences in neurohormonal response by measuring NT‐proBNP between patients with chronic heart failure treated with standard diuretic therapy and combined diuretic therapy Timepoint(s) of evaluation of this end point: 3 months INCLUSION CRITERIA: 1) written informed consent signed 2) Age: 18‐80 3) Patients with chronic heart failure (at reduced or preserved ejection fraction) 4) Patients discharged after hospitalization for acute heart failure (at least second episode of decompensation in the past 12 months) 5) Patients being treated with loop diuretics at the same or higher dosage of furosemide 40 mg (or equivalent) at the time of admission Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40