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Peritoneal Ultrafiltration in Cardio Renal Syndrome. (PURE)

Primary Purpose

Congestive Heart Failure

Status
Not yet recruiting
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
PolyCore (Polydextrin, L-Carnitine, D-xylitol)
Medical therapy including loop diuretic (furosemide) daily dose up to 2.5 mg/kg/day,
Sponsored by
Iperboreal Pharma Srl
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congestive Heart Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ospedale Ss. Annunziata
  • ASST FBF Sacco
  • Ospedale Monaldi

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

PolyCore PUF

Control

Arm Description

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.

Outcomes

Primary Outcome Measures

Composite 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.

Secondary Outcome Measures

6 min Walking distance
Change from the baseline
Quality of life tested with Minnesota Living with Heart Failure Questionnaire
Change from the baseline
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
Worsening of renal function
Estimated Glomerular Filtration Rate (eGFR) ≤20 ml/min
Cumulative daily dosage of loop diuretic
Change over the 6 months of study treatment,
Use of hospital resources
The number of days spent in-hospital because of HF exacerbation during the 6 months of study treatment
New York Heart Association (NYHA) class
Change from baseline
Number of patients requiring hospitalization
Hospitalization for infusional therapy with loop diuretic
Number of patients increasing of ≥50% the initial daily dose of loop diuretic
Change from baseline
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.

Full Information

First Posted
June 20, 2019
Last Updated
September 18, 2023
Sponsor
Iperboreal Pharma Srl
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1. Study Identification

Unique Protocol Identification Number
NCT03994874
Brief Title
Peritoneal Ultrafiltration in Cardio Renal Syndrome.
Acronym
PURE
Official Title
Peritoneal Ultrafiltration in Cardio Renal Syndrome to Prevent Heart Failure Exacerbation.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
November 2025 (Anticipated)
Study Completion Date
March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Iperboreal Pharma Srl

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congestive Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
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.
Allocation
Randomized
Enrollment
84 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PolyCore PUF
Arm Type
Experimental
Arm Description
PolyCore peritoneal ultrafiltration (PUF) (over the top of patient's prescribed heart failure medications), for 6 months.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Patients in the control arm (receiving no PUF therapy) will remain on their prescribed heart failure medications.
Intervention Type
Drug
Intervention Name(s)
PolyCore (Polydextrin, L-Carnitine, D-xylitol)
Other Intervention Name(s)
PolyCore peritoneal dialysis solution
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Medical therapy including loop diuretic (furosemide) daily dose up to 2.5 mg/kg/day,
Other Intervention Name(s)
Guidelines directed medical therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Composite end-point of mortality and worsening patient's condition
Description
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 6 months
Secondary Outcome Measure Information:
Title
6 min Walking distance
Description
Change from the baseline
Time Frame
At 3 and 6 months
Title
Quality of life tested with Minnesota Living with Heart Failure Questionnaire
Description
Change from the baseline
Time Frame
At 3 and 6 months
Title
Number of patients with decrease of NT pro-BNP (N-terminal pro brain natriuretic peptide)
Description
The number of patients with a decrease in NT pro-BNP level of ≥25% from baseline
Time Frame
At 3 and 6 months
Title
Worsening of renal function
Description
Estimated Glomerular Filtration Rate (eGFR) ≤20 ml/min
Time Frame
Up to 6 months
Title
Cumulative daily dosage of loop diuretic
Description
Change over the 6 months of study treatment,
Time Frame
6 months
Title
Use of hospital resources
Description
The number of days spent in-hospital because of HF exacerbation during the 6 months of study treatment
Time Frame
6 months
Title
New York Heart Association (NYHA) class
Description
Change from baseline
Time Frame
At 1, 3 and 6 months
Title
Number of patients requiring hospitalization
Description
Hospitalization for infusional therapy with loop diuretic
Time Frame
6 months
Title
Number of patients increasing of ≥50% the initial daily dose of loop diuretic
Description
Change from baseline
Time Frame
6 months
Title
Adverse Events
Description
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
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Arduino Arduini, MD
Phone
+41 79 7878312
Email
a.arduini@corequest.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edoardo Gronda, MD
Organizational Affiliation
Policlinico Milano - on behalf of Cardio Renal and Metabolism Working Group of the ANMCO
Official's Role
Study Director
Facility Information:
Facility Name
Ospedale Ss. Annunziata
City
Chieti
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mario Bonomini, MD
Facility Name
ASST FBF Sacco
City
Milano
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maurizio Gallieni, MD
Facility Name
Ospedale Monaldi
City
Napoli
Country
Italy
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giuseppe Pacileo, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Peritoneal Ultrafiltration in Cardio Renal Syndrome.

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