Congestive Heart Failure
Conditions
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.
Interventions
DRUGPolyCore (Polydextrin, L-Carnitine, D-xylitol)
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.
Sponsors
Iperboreal Pharma Srl
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
A blinded independent review committee, comprised of experienced cardiologist and nephrologists, who are non-participating investigators in this study, will be appointed to confirm the primary end-point.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite end-point of mortality and worsening patient's condition | Up to 7 months from randomization | * 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of life tested with Kansas City Cardiomyopathy Questionnaire (KCCQ) | At 3, 6 and 7 months from randomization | Change from the baseline |
| Number of patients with decrease of NT pro-BNP (N-terminal pro brain natriuretic peptide) | At 3, 6 and 7 months from randomization | The number of patients with a decrease in NT pro-BNP level of ≥25% from baseline |
| Worsening of renal function | Up to 7 months from randomization | Estimated Glomerular Filtration Rate (eGFR) ≤20 ml/min |
| Cumulative daily dosage of loop diuretic | Up to 7 months from randomization | Change over the 6 months of study treatment, |
| 6 min Walking distance | At 3, 6 and 7 months from randomization | Change from the baseline |
| New York Heart Association (NYHA) class | At 3, 6 and 7 months from randomization and during long-term FUs | Change from baseline |
| Number of patients requiring hospitalization | Up to 7 months from randomization | Hospitalization for infusional therapy with loop diuretic |
| Number of patients increasing of ≥50% the initial daily dose of loop diuretic | Up to 7 months from randomization | Change from baseline |
| Adverse Events | through study completion, an average of 1 year | 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. |
| Use of hospital resources | Up to 7 months from randomization | The number of days spent in-hospital because of HF exacerbation during the 6 months of study treatment |
Countries
Italy
Contacts
Primary ContactArduino Arduini, MD
Outcome results
None listed