Efficacy and Safety of XyloCore Peritoneal Dialysis Solution. (ELIXIR)

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.

Study Overview

• Status: Recruiting
• Conditions: End Stage Renal Disease
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Arduino Arduini, MD; Phone Number: +39.333.6409595; Email: a.arduini@iperboreal.com

Study Locations

• Denmark
  • Aarhus, Denmark
    • Recruiting
    • Aarhus University Hospital
    • Contact: Johan Povlsen, MD
  • Herlev, Denmark
    • Not yet recruiting
    • Herlev Og Gentofte Hospital
    • Contact: Rizwan Ahmed Butt, MD
  • Kolding, Denmark
    • Not yet recruiting
    • Kolding Medicinske Sygedomme
    • Contact: Marie Kjaergaard, MD
  • Roskilde, Denmark
    • Recruiting
    • Zealand University Hospital
    • Contact: Kirstine Møller Gliese, MD
• Germany
  • Düsseldorf, Germany
    • Recruiting
    • Dialysis Center DaVita
    • Contact: Thilo Krueger, MD
• Italy
  • Ascoli Piceno, Italy
    • Recruiting
    • Ospedale Madonna del Soccorso
    • Contact: Matthias Zeiler, MD
  • Bari, Italy
    • Not yet recruiting
    • Azienda Universitaria Ospedaliera di Bari
    • Contact: Loreto Gesualdo, MD
  • Chieti, Italy
    • Recruiting
    • Ospedale Ss. Annunziata
    • Contact: Mario Bonomini, MD; Email: mario.bonomini@unich.it
  • Colleferro, Italy
    • Recruiting
    • Ospedale Leopoldo Parodi Delfino
    • Contact: Luca Di Lullo, MD
  • Foggia, Italy
    • Recruiting
    • A.O.U. Ospedali Riuniti di Foggia
    • Contact: Giovanni Stallonee, MD
  • Milano, Italy
    • Recruiting
    • ASST Fatebenefratelli-Sacco -Ospedale Luigi Sacco
    • Contact: Maurizio Gallieni, MD
  • Modena, Italy
    • Not yet recruiting
    • Azienda ospedaliera universitaria di Modena
    • Contact: Gabriele Donati, MD
  • Napoli, Italy
    • Not yet recruiting
    • Università della Campania L.Vanvitelli
    • Contact: Silvio Borrelli, MD
  • Napoli, Italy
    • Recruiting
    • AOU Università degli studi della Campania
    • Contact: Francesco Trepiccione, MD
  • Piacenza, Italy
    • Recruiting
    • Ospedale AUSL "Guglielmo da Saliceto"
    • Contact: Roberto Scarpioni, MD
  • Roma, Italy
    • Recruiting
    • Policlinico Umberto I
    • Contact: Sandro Mazzaferro, MD
  • Roma, Italy
    • Not yet recruiting
    • Policlinico Gemelli
    • Contact: Giuseppe Grandaliano, MD
  • Roma, Italy
    • Not yet recruiting
    • Ospedale S.Eugenio
    • Contact: Roberto Palumbo, MD
  • San Benedetto Del Tronto, Italy
    • Recruiting
    • Ospedale C. e G. Mazzoni
    • Contact: Matthias Zailer, MD
  • Terni, Italy
    • Recruiting
    • Azienda Ospedaliera Terni
    • Contact: Luigi Vecchi, MD
  • Verona, Italy
    • Recruiting
    • Azienda Ospedaliera Universitaria Integrata Di Verona
    • Contact: Giovanni Gambaro, MD
  • Vicenza, Italy
    • Not yet recruiting
    • Ospedale San Bortolo
    • Contact: Monica Zanella, MD
• Spain
  • A Coruña, Spain
    • Not yet recruiting
    • University Hospital A Coruña Fundación Profesor Novoa Santos
    • Contact: Miguel Perez Fontan, MD
  • Badalona, Spain
    • Not yet recruiting
    • Hospital U. Germans Trias i Pujol
    • Contact: Marie Troya Saborido, MD
  • Barcelona, Spain
    • Recruiting
    • Fundacion Puigvert
    • Contact: Maria Alba Herreros, MD
  • Girona, Spain
    • Not yet recruiting
    • Hospital Universitario Josep Trueta
    • Contact: Claudia Castillo Devia
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario La Paz
    • Contact: Maria Bajo, MD
  • Madrid, Spain
    • Not yet recruiting
    • Fundacion jimenez diaz
    • Contact: Catalina Cleary, MD
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Ramon y Cajal
    • Contact: Haridian Sosa Barrios, MD
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Doce de Octubre
    • Contact: Paula Caro Espada, MD
  • Oviedo, Spain
    • Recruiting
    • Hospital Universitario Central de Asturias
    • Contact: Marie Rodriguez Suarez, MD
• Sweden
  • Halmstad, Sweden
    • Recruiting
    • Halland County Hospital of Halmstad
    • Contact: Karl Bjurström, MD
  • Stockholm, Sweden
    • Recruiting
    • Karolinska University Hospital
    • Contact: Olof Heimbürger, MD
• United Kingdom
  • Birmingham, United Kingdom
    • Recruiting
    • Heartlands Hospital
    • Contact: Jyoti Baharani, MD
  • Bradford, United Kingdom
    • Recruiting
    • St Luke's Hospital
    • Contact: Ahsan Syed, MD
  • Canterbury, United Kingdom
    • Recruiting
    • Kent and Canterbury Hospital
    • Contact: Nilesh Kumar Shah, MD
  • London, United Kingdom
    • Recruiting
    • Hammersmith Hospital
    • Contact: Richard Corbett, MD
  • Oxford, United Kingdom
    • Recruiting
    • Churchill Hospital
    • Contact: Udaya Udayaraj, MD
  • Reading, United Kingdom
    • Recruiting
    • Royal Berkshire Hospital
    • Contact: Oliver Flossmann, MD
  • Sheffield, United Kingdom
    • Recruiting
    • Sheffield Kidney Institute
    • Contact: Martin Wilkie, MD
  • Stoke-on-Trent, United Kingdom
    • Not yet recruiting
    • University Hospitals of North Midlands
    • Contact: Mark Lambie, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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)
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XyloCore peritoneal dialysis solution; 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; 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; Other Names: XyloCore 0.7 or 1.5 or 2.0
Active Comparator: Glucose peritoneal dialysis solution; 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; 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.; Other Names: Physioneal 40 or 35, Fixioneal 40 or 35, Dianeal, Balance, Bicavera, Bicanova, Equibalance

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Iperboreal Pharma Srl
• Investigators: Study Director: Arduino Arduini, MD, Iperboreal Pharma; Study Chair: Werner Kleophas, MD, DaVita Deutschland AG

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: ESRD; peritoneal dialysis
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: IP-001-18; 2019-004183-21 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No