Clinical trial NCT03994874: Peritoneal Ultrafiltration in Cardio Renal Syndrome.
Official title: Peritoneal Ultrafiltration in Cardio Renal Syndrome to Prevent Heart Failure Exacerbation.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Congestive Heart Failure
Lead sponsor: Iperboreal Pharma Srl
Sponsor class: INDUSTRY
First posted: 2019-06-21
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 no PUF therapy.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 yrs
* Left ventricular ejection fraction ≤60%
* NYHA Classification of III-IV despite guidelines directed medical therapy
* Right ventricular failure due to after load mismatch, addressed by the presence of tricuspid calve regurgitation (≥ moderate) 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 (equivalent to furosemide oral dose till 2.0 mg/kg/day), coupled with urinary sodium excretion ≤ mEq/L, confirmatory of loop diuretic resistance.
* 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 or BNP plasma concentration \> 250 pg/ml
* at least one episode of pulmonary or systemic congestion requiring high-dose intravenous diuretics (or diuretic combinations) in the 6 months befor the study enrollment
* An appropriate PUF technique candidate.
* Signed informed consent

Exclusion Criteria:

* Recipients of heart transplantation
* Presence of a mechanical circulatory support device;
* Hypertrophic obstructive cardiomyopathy;
* Uncontrolled hypertension with systolic blood pressure ≥ 160 mmHg
* 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;
* Female patients who are pregnant or breast-feeding or who wish to become pregnant during the period of the clinical trial and for three months later
* Female patients of childbearing age who do not use adequate contracteption.
* Unwilling and unable to give informed consent;
* Enrolment in another clinical trial involving medical or device based interventions.
* Hypersensibility to IMP components.
* Evidence of any condition that, according to the investigators' judgment, could expose the subject to undue risk and/or prevent the subject from participating in the study procedures and/or potentially afftecting the study quality data.

Primary outcomes:
measure: Composite end-point of mortality and worsening patient's condition
timeFrame: Up to 7 months from randomization
Secondary outcomes:
measure: 6 min Walking distance
timeFrame: At 3, 6 and 7 months from randomization
measure: Quality of life tested with Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: At 3, 6 and 7 months from randomization
measure: Number of patients with decrease of NT pro-BNP (N-terminal pro brain natriuretic peptide)
timeFrame: At 3, 6 and 7 months from randomization
measure: Worsening of renal function
timeFrame: Up to 7 months from randomization
measure: Cumulative daily dosage of loop diuretic
timeFrame: Up to 7 months from randomization
measure: Use of hospital resources
timeFrame: Up to 7 months from randomization
measure: New York Heart Association (NYHA) class
timeFrame: At 3, 6 and 7 months from randomization and during long-term FUs
measure: Number of patients requiring hospitalization
timeFrame: Up to 7 months from randomization
measure: Number of patients increasing of ≥50% the initial daily dose of loop diuretic
timeFrame: Up to 7 months from randomization
measure: Adverse Events
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Chieti
country: Italy
facility: Ospedale Ss. Annunziata
city: Milano
country: Italy
facility: ASST FBF Sacco
city: Napoli
country: Italy
facility: Ospedale Monaldi
Study officials:
affiliation: Policlinico Milano - on behalf of Cardio Renal and Metabolism Working Group of the ANMCO
name: Edoardo Gronda, MD
role: STUDY_DIRECTOR
References: