Efficacy and Safety of XyloCore Peritoneal Dialysis Solution.

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

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.

Patients should be enrolled if they are receiving 1, 2 or 3 diurnal exchanges of one of the following PD solutions (standard treatment): 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 (1.5%, 2.3%, 4.25% glucose) - and - one bag of Extraneal (7.5% Icodextrin) for the long-dwell exchange. Patients will be centrally randomized to the investigational product (XyloCore) or the glucose-only PD solution active comparator. Patients randomized to the control group will continue with their prescription of standard treatment with 1, 2 to 3 daily (short-dwell) exchanges of Physioneal, Fixioneal, Dianeal, Balance, Bicavera, Bicanova or Equibalance PD solution. Patients randomized to XyloCore will receive XyloCore Low, Medium or High Strength according to the osmotic strength (glucose concentration) of their prerandomization prescribed PD solution. All patients will keep being prescribed Extraneal (7.5% Icodextrin) for the nocturnal (long-dwell) exchange. The osmotic strength and number of diurnal short dwell exchanges may be modified by the investigator as clinically required. PD prescriptions in both treatment arms should be tailored to reach the minimum target of a total Kt/V of > 1.7 per week throughout the study. A stratified randomization scheme will be employed to ensure balanced allocation across the two treatment groups of patients with diabetes and of patients treated with only 1 diurnal exchange. Randomization will be performed centrally via a web-based system according to a computer-generated randomization list. The study is open-label with blinded evaluator (primary endpoint), without blinding of patients or clinical staff.

INCLUSION CRITERIA:

1. Age ≥18 years
2. Diagnosed with ESRD and treated with CAPD in the last 3 months
3. In stable clinical condition during the 3 months before screening as demonstrated by the absence of non-elective hospitalization and major cardiovascular events
4. Have not experienced peritonitis episodes in the last 3 months
5. In treatment with prescribed Extraneal (nocturnal exchange bag solution) for at least 1 month
6. In treatment with 1, 2 or 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)
7. Kt/V urea measurement > 1.7 per week at Baseline Visit
8. Followed/treated by the participating clinical Center/Investigator in the last three months
9. Understanding the nature of the study and providing their informed consent to participation.

EXCLUSION CRITERIA:

1. History of drug or alcohol abuse in the six months prior to entering the protocol
2. In treatment with androgens
3. Clinically significant abnormal liver function test (ɣ-GT > 4 times the upper normal limit)
4. Acute infectious conditions (i.e.: pulmonary infection, acute hepatitis, high or low urinary tract infections, renal parenchymal infection, pericarditis, etc)
5. Expected patient's survival shorter than the trial duration
6. History of L-Carnitine therapy or use in the month prior to entering the protocol
7. Have used any investigational drug in the 3 months prior to entering the protocol
8. Female patients who are pregnant or breast-feeding.
9. Female patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception
10. Patients affected by Primary Hyperoxaluria as per known medical therapy
11. Patients with serum levels of uric acid > 7.2 mg/dl (male and postmenopausal women) or > 6.0 mg/dl (premenopausal women)
12. Patients with a major cardiovascular event in the last 3 months
13. Patients with advanced cardiac failure (NYHA 4)
14. Hypersensitivity to any of the constituents of the study IMPs.
15. Any contraindication to the prescribed Peritoneal Dialysis solutions (for long-dwell and short-dwell exchange) as per each product SmPC.
16. Participants with medical history of oxalate or lactate abnormalities considered clinically significant by the investigator.
17. 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.