Efficacy and Safety of XyloCore Peritoneal Dialysis Solution.

Study Overview
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Brief Summary
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Randomized, controlled, parallel groups, open-label, blinded end-point assessment, multicenter study, comparing the effects of a low glucose peritoneal dialysis solution, XyloCore, to glucose solutions (Physioneal, Fixioneal, Dianeal, Balance, Bicavera, Bicanova or Equibalance) only regimen, in patients with End-Stage Renal Disease (ESRD) receiving Continuous Ambulatory Peritoneal Dialysis (CAPD), over a 6-month study period.

Detailed Description
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Patients should be enrolled if they are receiving 2 or 3 diurnal (short dwell) exchange bag solution of Physioneal 35 or 40 (including Clear-Flex bag), Fixioneal 35 or 40, Dianeal or Dianeal Low Calcium (1.36%, 2.27% or 3.86% glucose), or Balance, Bicavera, Bicanova or Equibalance (1.25%, 2.3%, 4.5% glucose) and Extraneal (7.5% Icodextrin) for the long-dwell exchange. Patients will be centrally randomized to receive the investigational product (XyloCore) or the active control (Physioneal, Fixioneal, Dianeal, Balance, Bicavera, Bicanova or Equibalance). A stratified randomization scheme will be employed to ensure a balanced allocation of patients with diabetes across the two treatment groups. Patients randomized to XyloCore will receive 2 to 3 bags of XyloCore (Low, Medium or High Strenght) with an osmotic strength comparable to their pre-randomization prescription of the glucose peritoneal dialysis solution. Patients randomized to the control group will continue the 2 to 3 daily (short-dwell) exchanges of Physioneal, Fixioneal, Dianeal, Balance, Bicavera, Bicanova or Equibalance. All patients will receive Extraneal (7.5% Icodextrin) for nocturnal (long-dwell) exchange. The osmotic strength and number of diurnally short dwells exchanges should be modified by the investigator as clinically required. PD prescriptions in both treatment arms are tailored to reach a minimum target of total Kt/V of 1.7 per week throughout the study. The study will be single-blinded (outcomes assessor), without blinding of patients or clinical staff.

Official Title
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A Study to EvaLuate the EffIcacy and Safety of XyloCore, a Glucose SparIng ExpeRimental Solution, for Peritoneal Dialysis

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: XyloCore Low Strenght, XyloCore Medium Strenght, XyloCore High Strenght
* Drug: 1.36%, 1.5%, 2.27%, 2.5%, 3.86%, 2.25% Glucose PD Solution


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Age ≥18 years Diagnosed with ESRD and treated with CAPD in the last 3 months In stable clinical condition during the 3 months before screening as demonstrated by the absence of non-elective hospitalization and major cardiovascular events Have not experienced peritonitis episodes in the last 3 months In treatment with prescribed Extraneal (nocturnal exchange bag solution) for at least 1 month In treatment with 2 to 3 diurnal exchange bag solution of prescribed Phisioneal (including Clear-Flex bag), Fixioneal, Dianeal or Dianeal Low Calcium (1.36%, 2.27% or 3.86% glucose), or Balance, Bicavera, Bicanova or Equibalance (1.25%, 2.3%, 4.5% glucose) Kt/V urea measurement > 1.7 per week at Baseline Visit Followed/treated by the participating clinical Center/Investigator in the last three months Understanding the nature of the study and providing their informed consent to participation. EXCLUSION CRITERIA: History of drug or alcohol abuse in the six months prior to entering the protocol In treatment with androgens Clinically significant abnormal liver function test (ɣ-GT > 4 times the upper normal limit) Acute infectious conditions (i.e.: pulmonary infection, acute hepatitis, high or low urinary tract infections, renal parenchymal infection, pericarditis, etc) Expected patient's survival shorter than the trial duration History of L-Carnitine therapy or use in the month prior to entering the protocol Have used any investigational drug in the 3 months prior to entering the protocol Female patients who are pregnant or breast-feeding. Female patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception Patients affected by Primary Hyperoxaluria as per known medical therapy Patients with serum levels of uric acid > 7.2 mg/dl (male and postmenopausal women) or > 6.0 mg/dl (premenopausal women) Patients with a major cardiovascular event in the last 3 months Patients with advanced cardiac failure (NYHA 4) Hypersensitivity to any of the constituents of the study IMPs. Any contraindication to the prescribed Peritoneal Dialysis solutions (for long-dwell and short-dwell exchange) as per each product SmPC. Participants with medical history of oxalate or lactate abnormalities considered clinically significant by the investigator. History or evidence of any other medical, neurological or psychological condition that would expose the subject to an undue risk of a significant AE or interfere with study assessments during the course of the trial as determined by the clinical judgment of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization will be performed centrally via a web-based system, with stratification according to the presence or absence of diabetes.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XyloCore peritoneal dialysis solution<br>Patients will receive 2 to 3 daily (short-dwell) exchanges with XyloCore of an osmotic strength comparable to their pre-randomization prescription of glucose peritoneal dialysis solution (XyloCore Low, Medium and High Strenght have an osmotic strength comparable to Physioneal, Fixioneal or Dianeal 1.36%, 2.27%, 3.86% glucose, respectively, and Balance, Bicavera, Bicanova or Equibalance with 1.5%, 2.5%, 4.25% glucose, respectively). All patients will receive Extraneal (7.5% Icodextrin) for nocturnal (long-dwell) exchange. | Drug: XyloCore Low Strenght, XyloCore Medium Strenght, XyloCore High Strenght<br>* XyloCore Low Strenght: 0.7% Xylitol, 0.5% Glucose, and 0.02% L-carnitine - or - XyloCore Medium Strenght: 1.5% Xylitol, 0.5% Glucose, and 0.02% L-carnitine - or - XyloCore High Strenght: 2.0% Xylitol, 1.5% Glucose, and 0.02% L-carnitine<br>* Other names: XyloCore 0.7 or 1.5 or 2.0;|
| Active Comparator: Glucose peritoneal dialysis solution<br>Patients randomized to glucose solution will continue the 2 to 3 daily (short-dwell) exchanges of Physioneal 40 or 35, Fixioneal 40 or 35 or Dianeal (1.36%, 2.27%, 3.86% glucose), Balance, Bicavera, Bicanova or Equibalance (1.5%, 2.5%, 4.25% glucose) with the same osmotic strength of their pre-randomization prescription. All patients will receive Extraneal (7.5% Icodextrin) for nocturnal (long-dwell) exchange. | Drug: 1.36%, 1.5%, 2.27%, 2.5%, 3.86%, 2.25% Glucose PD Solution<br>* Physioneal 35 or 40 (including Clear-Flex bag), Fixioneal 35 or 40, Dianeal or Dianeal Low Calcium have 1.36%, 2.27% or 3.86% glucose; Balance, Bicavera, Bicanova or Equibalance have 1.25%, 2.3%, 4.5% glucose.<br>* Other names: Physioneal 40 or 35, Fixioneal 40 or 35, Dianeal, Balance, Bicavera, Bicanova, Equibalance;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total weekly Kt/Vurea | To measure solutes and calculate peritoneal and renal Kt/V (summing up to total Kt/V), dialysate outflow and urine covering 24 hours will be collected, the volumes will be determined, and a blood sample will be taken | 24-week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in HbA1c (glycated haemoglobin) | Change from baseline value | 6 months | 
| Insulin | Changes from the baseline value | 6 months | 
| LDL cholesterol | Changes from the baseline value | 6 months | 
| HDL cholesterol | Change from the baseline value | 6 months | 
| Serum triglycerides | Change from the baseline value | 6 months | 
| Total cholesterol | Changes from the baseline | 6 months | 
| Hemoglobin | Changes from the baseline value | 6 months | 
| EPO requirements | Change from the baseline | 6 months | 
| Fatigue measured through a validated instrument | Changes from the baseline | 6 months | 
| Peritoneal ultrafiltration | Changes from baseline | 6 months | 
| Diuresis (or 24 hours urinary volume) | Changes from baseline | 6 months | 
| Residual renal function | Changes from baseline - measured as the arithmetic mean of urinary urea and creatinine clearance | 6 months | 
| Adverse Events | Information about all adverse events, whether volunteered by the patient, discovered by investigator questioning, or detected through physical examination, laboratory test or other means, will be collected, recorded and followed as appropriate. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peritoneal dialysis, ESRD