Efficacy and Safety of XyloCore Peritoneal Dialysis Solution.

End Stage Renal Disease Clinical Trial

— ELIXIR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03994471
• Other study ID #: IP-001-18
• Secondary ID: 2019-004183-21
• Status: Recruiting
• Phase: Phase 3
• Start date: December 14, 2022
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Iperboreal Pharma Srl
• Contact: Arduino Arduini, MD
• Phone: +39.333.6409595
• Email: a.arduini[@]iperboreal.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (?-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.

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic

Intervention

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
• 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.

Locations

Country	Name	City	State
Denmark	Aalborg University	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Zealand University Hospital	Roskilde
Germany	Dialysis Center DaVita	Düsseldorf
Italy	Ospedale Madonna del Soccorso	Ascoli Piceno
Italy	Ospedale Santa Maria Annunziata	Bagno A Ripoli
Italy	Azienda Universitaria Ospedaliera di Bari	Bari
Italy	ASST Spedali Civili di Brescia	Brescia
Italy	Ospedale SS. Annunziata	Chieti
Italy	IRCCS Policlinico San Martino	Genova
Italy	Ospedale Civile San Salvatore	L'Aquila
Italy	ASST Fatebenefratelli-Sacco -Ospedale Luigi Sacco	Milano
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria di Modena	Modena
Italy	AOU Università degli studi della Campania	Napoli
Italy	Università della Campania L.Vanvitelli	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Ospedale AUSL "Guglielmo da Saliceto"	Piacenza
Italy	Ospedale S.Eugenio	Roma
Italy	Ospedale C. e G. Mazzoni	San Benedetto Del Tronto
Italy	Azienda Ospedaliera Terni	Terni
Italy	Ospedale San Giovanni Bosco	Torino
Italy	Azienda Ospedaliera Universitaria Integrata di Verona	Verona
Spain	University Hospital A Coruña Fundación Profesor Novoa Santos	A Coruña
Spain	Hospital U. Germans Trias i Pujol	Badalona
Spain	Fundaciòn Puigvert	Barcelona
Spain	Hospital Universitario Josep Trueta	Girona
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Central De Asturias	Oviedo
Sweden	Halland County Hospital of Halmstad	Halmstad
Sweden	Karolinska University Hospital	Stockholm
United Kingdom	Heartlands Hospital	Birmingham
United Kingdom	St Luke's Hospital	Bradford
United Kingdom	University Hospitals Sussex	Brighton
United Kingdom	Kent and Canterbury Hospital	Canterbury
United Kingdom	Hammersmith Hospital	London
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Sheffield Kidney Institute	Sheffield
United Kingdom	University Hospitals of North Midlands	Stoke-on-Trent

Sponsors (1)

Lead Sponsor	Collaborator
Iperboreal Pharma Srl

Countries where clinical trial is conducted

Denmark,  Germany,  Italy,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Changes in HbA1c (glycated haemoglobin)	Change from baseline value	6 months
Secondary	Insulin	Changes from the baseline value	6 months
Secondary	LDL cholesterol	Changes from the baseline value	6 months
Secondary	HDL cholesterol	Change from the baseline value	6 months
Secondary	Serum triglycerides	Change from the baseline value	6 months
Secondary	Total cholesterol	Changes from the baseline	6 months
Secondary	Hemoglobin	Changes from the baseline value	6 months
Secondary	EPO requirements	Change from the baseline	6 months
Secondary	Fatigue measured through a validated instrument	Changes from the baseline	6 months
Secondary	Peritoneal ultrafiltration	Changes from baseline	6 months
Secondary	Diuresis (or 24 hours urinary volume)	Changes from baseline	6 months
Secondary	Residual renal function	Changes from baseline - measured as the arithmetic mean of urinary urea and creatinine clearance	6 months
Secondary	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