Randomized, controlled, unblinded, adaptive design clinical trial to evaluate the safety and efficacy of PolyCore (Polydextrin, L-Carnitine, D-xylitol) peritoneal ultrafiltration (PUF) in patients with heart failure and reduced ejection fraction (HFrEF).
The study will include adults HFrEF patients, that despite guidelines directed medical therapy still retain a congestive heart failure (HF) picture. During the study, patients should remain on their prescribed heart failure medications and the same dosing schedule for the duration of the study unless investigators determine medically necessary to change. Patients will be assigned randomly to receive either PolyCore PUF (over the top of their prescribed heart failure medications), for 6 months, or to the control arm receiving stable medical therapy according to international guidelines and comprehensive of loop diuretic (furosemide) dose till to 2.5mg/kg/day, without PUF therapy. The PUF ultrafiltration will be performed with a single nightly exchange, with 2 liters PolyCore solution, lasting 12-14 hours, for 6 months. An independent data safety monitoring board (DSMB) will be convened for this study and will review the results of the trial at regular intervals to protect patients participating in the study. An adaptive interim analysis will be performed when in each group 20 patients have completed 6 months in the study, for analysis of the primary outcome. The purpose of the adaptive interim analysis is to calculate the final study sample size.The DSMB will closely examine the interim primary efficacy results, respecting the confidentiality and integrity of data, to investigate the final sample sizes necessary to complete the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
84
A single nightly exchange, with 2 liters PolyCore solution, lasting 12-14 hours. Patients should remain on their prescribed heart failure medications and the same dosing schedule for the duration of the study unless investigators determine medically necessary to change.
Ospedale Ss. Annunziata
Chieti, Italy
RECRUITINGASST FBF Sacco
Milan, Italy
RECRUITINGOspedale Monaldi
Naples, Italy
RECRUITINGComposite end-point of mortality and worsening patient's condition
* patient's mortality - or * the need of increasing of ≥50% the initial daily dose of loop diuretic - or * the hospitalization for infusional therapy with loop diuretic based on the lack of adequate response to maximal dose of oral furosemide (\>2.5 mg/kg/day) - or * requiring other methods of treatment \[i.e. PUF or hemodialysis\], based on persistence of high venous congestion (detected with central venous pressure measurement: \>8 mm Hg or dilated inferior cava vein, without respiratory change, measured with focused abdominal echography, and coupled with body weight increase of 1 kg or more in the last 24 hrs.
Time frame: Up to 7 months from randomization
6 min Walking distance
Change from the baseline
Time frame: At 3, 6 and 7 months from randomization
Quality of life tested with Kansas City Cardiomyopathy Questionnaire (KCCQ)
Change from the baseline
Time frame: At 3, 6 and 7 months from randomization
Number of patients with decrease of NT pro-BNP (N-terminal pro brain natriuretic peptide)
The number of patients with a decrease in NT pro-BNP level of ≥25% from baseline
Time frame: At 3, 6 and 7 months from randomization
Worsening of renal function
Estimated Glomerular Filtration Rate (eGFR) ≤20 ml/min
Time frame: Up to 7 months from randomization
Cumulative daily dosage of loop diuretic
Change over the 6 months of study treatment,
Time frame: Up to 7 months from randomization
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Use of hospital resources
The number of days spent in-hospital because of HF exacerbation during the 6 months of study treatment
Time frame: Up to 7 months from randomization
New York Heart Association (NYHA) class
Change from baseline
Time frame: At 3, 6 and 7 months from randomization and during long-term FUs
Number of patients requiring hospitalization
Hospitalization for infusional therapy with loop diuretic
Time frame: Up to 7 months from randomization
Number of patients increasing of ≥50% the initial daily dose of loop diuretic
Change from baseline
Time frame: Up to 7 months from randomization
Adverse Events
Information about all adverse events, whether volunteered by the patient, discovered by investigator questioning, or detected through physical examination, laboratory or instrumental test, will be collected, recorded and followed as appropriate.
Time frame: through study completion, an average of 1 year