Clinical trial NCT03994471: Efficacy and Safety of XyloCore Peritoneal Dialysis Solution.
Official title: A Study to EvaLuate the EffIcacy and Safety of XyloCore, a Glucose SparIng ExpeRimental Solution, for Peritoneal Dialysis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: End Stage Renal Disease
Keywords: peritoneal dialysis
ESRD
Lead sponsor: Iperboreal Pharma Srl
Sponsor class: INDUSTRY
First posted: 2019-06-21
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization will be performed centrally via a web-based system, with stratification according to the presence or absence of diabetes.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Total weekly Kt/Vurea
timeFrame: 24-week
Secondary outcomes:
measure: Changes in HbA1c (glycated haemoglobin)
timeFrame: 6 months
measure: Insulin
timeFrame: 6 months
measure: LDL cholesterol
timeFrame: 6 months
measure: HDL cholesterol
timeFrame: 6 months
measure: Serum triglycerides
timeFrame: 6 months
measure: Total cholesterol
timeFrame: 6 months
measure: Hemoglobin
timeFrame: 6 months
measure: EPO requirements
timeFrame: 6 months
measure: Fatigue measured through a validated instrument
timeFrame: 6 months
measure: Peritoneal ultrafiltration
timeFrame: 6 months
measure: Diuresis (or 24 hours urinary volume)
timeFrame: 6 months
measure: Residual renal function
timeFrame: 6 months
measure: Adverse Events
timeFrame: 6 months
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Roskilde
country: Denmark
facility: Zealand University Hospital
city: Düsseldorf
country: Germany
facility: Dialysis Center DaVita
city: Ascoli Piceno
country: Italy
facility: Ospedale Madonna del Soccorso
city: Bagno A Ripoli
country: Italy
facility: Ospedale Santa Maria Annunziata
city: Bari
country: Italy
facility: Azienda Universitaria Ospedaliera di Bari
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Chieti
country: Italy
facility: Ospedale SS. Annunziata
city: Genova
country: Italy
facility: IRCCS Policlinico San Martino
city: L'Aquila
country: Italy
facility: Ospedale Civile San Salvatore
city: Milano
country: Italy
facility: ASST Fatebenefratelli-Sacco -Ospedale Luigi Sacco
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: Azienda Ospedaliera Universitaria di Modena
city: Napoli
country: Italy
facility: AOU Università degli studi della Campania
city: Napoli
country: Italy
facility: Università della Campania L.Vanvitelli
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Piacenza
country: Italy
facility: Ospedale AUSL "Guglielmo da Saliceto"
city: Roma
country: Italy
facility: Ospedale S.Eugenio
city: San Benedetto Del Tronto
country: Italy
facility: Ospedale C. e G. Mazzoni
city: Terni
country: Italy
facility: Azienda Ospedaliera Terni
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata di Verona
city: A Coruña
country: Spain
facility: University Hospital A Coruña Fundación Profesor Novoa Santos
city: Badalona
country: Spain
facility: Hospital U. Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Fundaciòn Puigvert
city: Girona
country: Spain
facility: Hospital Universitario Josep Trueta
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Oviedo
country: Spain
facility: Hospital Universitario Central De Asturias
city: Halmstad
country: Sweden
facility: Halland County Hospital of Halmstad
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital
city: Bradford
country: United Kingdom
facility: St Luke's Hospital
city: Brighton
country: United Kingdom
facility: University Hospitals Sussex
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Kidney Institute
city: Stoke-on-Trent
country: United Kingdom
facility: University Hospitals of North Midlands
Study officials:
affiliation: Iperboreal Pharma
name: Arduino Arduini, MD
role: STUDY_DIRECTOR
affiliation: DaVita Deutschland AG
name: Werner Kleophas, MD
role: STUDY_CHAIR
References: