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Peritoneal Ultrafiltration in Cardio Renal Syndrome. (PURE)

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ClinicalTrials.gov Identifier: NCT03994874
Recruitment Status : Not yet recruiting
First Posted : June 21, 2019
Last Update Posted : June 21, 2019
Sponsor:
Information provided by (Responsible Party):
CoreQuest, Switzerland

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).

Condition or disease Intervention/treatment Phase
Congestive Heart Failure Drug: PolyCore (Polydextrin, L-Carnitine, D-xylitol) Drug: Medical therapy including loop diuretic (furosemide) daily dose up to 2.5 mg/kg/day, Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
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.
Primary Purpose: Treatment
Official Title: Peritoneal Ultrafiltration in Cardio Renal Syndrome to Prevent Heart Failure Exacerbation.
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: PolyCore PUF
PolyCore peritoneal ultrafiltration (PUF) (over the top of patient's prescribed heart failure medications), for 6 months.
Drug: PolyCore (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.
Other Name: PolyCore peritoneal dialysis solution

Active Comparator: Control
Patients in the control arm (receiving no PUF therapy) will remain on their prescribed heart failure medications.
Drug: Medical therapy including loop diuretic (furosemide) daily dose up to 2.5 mg/kg/day,
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.
Other Name: Guidelines directed medical therapy




Primary Outcome Measures :
  1. Composite end-point of mortality and worsening patient's condition [ Time Frame: Up to 6 months ]
    • 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 :
  1. 6 min Walking distance [ Time Frame: At 3 and 6 months ]
    Change from the baseline

  2. Quality of life tested with Minnesota Living with Heart Failure Questionnaire [ Time Frame: At 3 and 6 months ]
    Change from the baseline

  3. Number of patients with decrease of NT pro-BNP (N-terminal pro brain natriuretic peptide) [ Time Frame: At 3 and 6 months ]
    The number of patients with a decrease in NT pro-BNP level of ≥25% from baseline

  4. Worsening of renal function [ Time Frame: Up to 6 months ]
    Estimated Glomerular Filtration Rate (eGFR) ≤20 ml/min

  5. Cumulative daily dosage of loop diuretic [ Time Frame: 6 months ]
    Change over the 6 months of study treatment,

  6. Use of hospital resources [ Time Frame: 6 months ]
    The number of days spent in-hospital because of HF exacerbation during the 6 months of study treatment

  7. New York Heart Association (NYHA) class [ Time Frame: At 1, 3 and 6 months ]
    Change from baseline

  8. Number of patients requiring hospitalization [ Time Frame: 6 months ]
    Hospitalization for infusional therapy with loop diuretic

  9. Number of patients increasing of ≥50% the initial daily dose of loop diuretic [ Time Frame: 6 months ]
    Change from baseline

  10. Adverse Events [ Time Frame: 6 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03994874


Contacts
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Contact: Arduino Arduini, MD +41 79 7878312 a.arduini@corequest.ch

Sponsors and Collaborators
CoreQuest, Switzerland
Investigators
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Study Director: Edoardo Gronda, MD Policlinico Milano

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Responsible Party: CoreQuest, Switzerland
ClinicalTrials.gov Identifier: NCT03994874     History of Changes
Other Study ID Numbers: CQ012019
First Posted: June 21, 2019    Key Record Dates
Last Update Posted: June 21, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardio-Renal Syndrome
Cardiovascular Diseases
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Furosemide
Diuretics
Sodium Potassium Chloride Symporter Inhibitors
Natriuretic Agents
Physiological Effects of Drugs
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action