Cross-over, 2-sequence, 2-treatment, 2-period single-centre, phase IV, randomized, open label study.
Peritoneal dialysis (PD) is a technique that has been successfully used for the treatment of refractory heart failure to diuretics. In patients on PD, the harmful effects of sodium retention become even greater, resulting in fluid overload, hypertension and left ventricular hypertrophy in more than half of the PD population. This is due to the fact that the accumulation of sodium in the skin interstitium would generate an inflammatory environment and, therefore, the activation of growth and fibrogenic factors with a consequent increase in cardiac muscle mass. In patients with HF receiving PD, therefore, it is necessary to reduce salt intake with diet, as well as to ensure adequate elimination through available medical treatments and elimination of Na through the most appropriate dialysis technique. In recent years, a new player has joined the treatment of HF: iSGLT2, an oral hypoglycaemic drug. ISGLT2 promotes natriuresis thanks to its well-known mechanism of inhibition of Na and glucose co-transporter. Also promoting excretion of Na at the distal tubule level due to increased tubular osmotic pressure secondary to glycosuria, as well as by direct inhibition of NH3 channels reabsorbing Na and Hydrogens. The purpose of the study is to analyse whether the use of an SGLT2 inhibitor (Dapagliflozin) in patients with CKD and HF treated with peritoneal dialysis can benefit patients in terms of increased total elimination of sodium and water. In this study, dapagliflozin will be used together with established drug therapy for patients with HF, including concomitant diuretic therapy. after randomization, the patient will be divided in two groups and they will receive the study drug or placebo for 8 weeks and, after a 4-week wash out, each patient will switch groups for further 8 weeks to receive standard of care or standard of care plus Dapaglifozin as appropriate. The study will end with a safety extension study in which all patients will take Dapagliflozin for a further 8 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
10 mg once per day, oral tablets
Hospital Clínico Universitario de Valencia
Valencia, Spain
RECRUITINGMean difference of the sum between 24-h natriuresis and the daily sodium elimination in the peritoneal effluent (mEq/L) in the 3rd (8th week) visit control compared with the 6th (20th week)visit control.
To explore the effect of iSGLT2 in natriuresis and the peritoneal elimination of sodium in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months
Mean difference of the sum between the volume of diuresis in 24 hours and the daily peritoneal effluent ultrafiltration rate (ml/24hours) in the 3rd (8th week) visit control compared with the 6th (20th week) visit control.
To explore the effect of the use of iSGLT2 in diuresis and, in the peritoneal net ultrafiltration in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months
Mean difference of the sum between the volume of diuresis in 24 hours and the daily peritoneal effluent ultrafiltration rate (ml/24hours) in the 2nd (4th week) visit control compared with the 5th (16th week) visit control.
To explore the effect of the use of iSGLT2 in diuresis and, in the peritoneal net ultrafiltration in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months
Mean difference of the sum between 24-h natriuresis and the daily sodium elimination in the peritoneal effluent (mEq/L) in the 2nd visit control compared with the 5th visit control.
To explore the effect of iSGLT2 in natriuresis and the peritoneal elimination of sodium in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months
Mean difference between the hydration percentage: Total Body Water%, Extracellular Water% , Intracellular Water%, Plasma Fluid, Interstitial Fluid by bioimpedance in the 3rd visit control compared with the 6th visit control.
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To explore the effect of the use of iSGLT2 in the normalization of extracellular volume in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months
Collection of chemistry parameters: Mean change and standard deviations in Peritoneal Fluid Glucose Ratio and Sodium concentration in the effluent peritoneal dialysis fluid sample in the 3rd visit control compared with the 6th visit control.
To evaluate the effect of the use of iSGLT2 in Glucose and sodium homeostasis in the peritoneal fluid effluent in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months
Mean change and standard deviations in Peritoneal Fluid Glucose Ratio (D4/D0) and Sodium (mEq/24hr) concentration in the effluent peritoneal dialysis fluid sample in the 2nd visit control compared with the 5th visit control.
To evaluate the effect of the use of iSGLT2 in Glucose and sodium homeostasis in the peritoneal fluid effluent in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months
Mean Difference in NYHA Classification, Ultrasounds parameters for the evaluation of venous congestion and BNP (ng/ml), CA 125 (ng/ml) in the blood sample in the 3rd visit control compared with the 6th visit control.
To evaluate the effect of the use of iSGLT2 in the clinical and laboratory parameters in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months
Mean difference in Ca125 (U/min), IL-6 (pg/min), in the effluent peritoneal dialysis fluid sample in the 3rd visit control compared with the 6th visit control.
To study the effect of the use of iSGLT2 in the inflammatory state of the peritoneal membrane in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months
Mean Change in the total amount of loop diuretic and thiazide treatment (mg/daily) in the 3rd visit control compared with the 6th visit control.
To evaluate the effect of the use of iSGLT2 in dose reduction of diuretics and the need for diuretic therapy in patients with CKD and refractory HF treated with peritoneal dialysis.
Time frame: Through study completion, an average of 4 months