Peritoneal Ultrafiltration in Cardio Renal Syndrome.
Peritoneal Ultrafiltration in Cardio Renal Syndrome to Prevent Heart Failure Exacerbation.
PhasePhase 1/Phase 2
Lead SponsorCoreQuest, Switzerland
StatusNot yet recruiting
Indication/ConditionCongestive Heart Failure
Intervention/TreatmentPolyCore (Polydextrin, L-Carnitine, D-xylitol) [polydextrin (116142), levocarnitine (43378), xylitol (81229)] Medical therapy including loop diuretic (furosemide) daily dose up to 2.5 mg/kg/day,
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.
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.
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.
PolyCore peritoneal ultrafiltration (PUF) (over the top of patient's prescribed heart failure medications), for 6 months.
Patients in the control arm (receiving no PUF therapy) will remain on their prescribed heart failure medications.
Inclusion Criteria: Age ≥18 yrs ≥ 3 months follow-up in the clinic Left ventricular ejection fraction ≤40% NYHA Classification of III-IV despite guidelines directed medical therapy Hospitalized for heart failure Right ventricular failure due to after load mismatch, addressed by the presence of tricuspid valve regurgitation and by the disproportioned increase of the right atrial pressure (RAP) versus the capillary wedge pressure (CWP) with a ratio >0,65 detected with right heart catheterization performed after stable medical therapy according to international guidelines and comprehensive of loop diuretic (furosemide) dose till to 2.5mg/kg/day, coupled with urinary sodium excretion ≤ 70 mEq/L/day, confirmatory of loop diuretic resistance (4). Cava vein enlargement (inner diameter, detected with focused echocardiography, between 1,5 and 2,5 cm, with respiratory collapse <50% or absent due to intravascular fluid overload) Decreased kidney function addressed by the measurement of glomerular filtration rate (GFR) urea clearance + creatinine clearance/2 (>15 ml/min/1,73 m2) NT pro-BNP plasma concentration > 1000 pg/ml. The presence of at least one hospitalization for HF lasting 3 days or more in the 6 months before the study enrolment An appropriate PUF technique candidate. Signed informed consent Exclusion Criteria: Recipients of heart transplantation Presence of a mechanical circulatory support device; Isolated Right Heart Failure; Isolated Left Ventricular diastolic dysfunction; Hypertrophic obstructive cardiomyopathy; Severe valvular stenosis; Restrictive cardiomyopathy; Acute coronary syndrome ≤ 6 months before; Active myocarditis Cardiosurgical or Endo-radiological heart procedures ≤ 6 months before Cardiac resynchronization therapy (CRT) implantation or upgrading of pacemaker (PM) or implantable cardioverter defibrillator (ICD) to CRT ≤ 6 months before; Patient with end-stage renal disease, GFR urea clearance + creatinine clearance/2 (<15 ml/min/1,73 m2 GFR) Any major organ transplant (liver, lung, kidney) Lung embolism ≤ 6 months before; Fibrotic lung disease; Liver Cirrhosis; Absolute contraindication to peritoneal catheter implantation; Logistical and or organizational contra-indication to treatment Active malignancy; Pregnancy; Unwilling and unable to give informed consent; Enrolment in another clinical trial involving medical or device based interventions.