Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis

Mario Bonomini; Simon Davies; Werner  Kleophas; Mark Lambie; Gianpaolo Reboldi; Lorenzo De Liberato; José Carolino Divino-Filho; Olof Heimburger; Alberto Ortiz; Johan Povlsen; Massimo Lacobelli; Tommaso Prosdocimi; Arduino Arduini

doi:10.1177/08968608241274106

Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis

Mario Bonomini, Simon Davies, Werner Kleophas, Mark Lambie, Gianpaolo Reboldi, Lorenzo De Liberato, José Carolino Divino-Filho, Olof Heimburger, Alberto Ortiz, Johan Povlsen, Massimo Lacobelli, Tommaso Prosdocimi, Arduino Arduini

Institut for Klinisk Medicin - Nyresygdomme

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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Abstract

Peritoneal dialysis adoption and technique survival is affected by limitations related to peritoneal membrane longevity and metabolic alterations. Indeed, almost all peritoneal dialysis fluids exploit glucose as an osmotic agent that rapidly diffuses across the peritoneal membrane, potentially resulting in metabolic abnormalities such as hyperglycemia, hyperinsulinemia, obesity, and hyperlipidemia. Moreover, glucose-degradation products generated during heat sterilization, other than glucose itself, induce significant morphological and functional changes in the peritoneum leading to ultrafiltration failure. The partial substitution of glucose with osmotic agents characterized by a better local and systemic biocompatibility has been suggested as a potential strategy to innovate peritoneal dialysis fluids. The approach aims to minimize glucose-associated toxicity, preserving the peritoneal membrane welfare and counteracting common comorbidities. In this work, we report the clinical trial design of ELIXIR, a phase III randomized, controlled, blinded outcome assessment study comparing Xylocore^®, an innovative formulation based on Xylitol and l-carnitine, to standard glucose-based regimens, in end-stage kidney disease patients treated with continuous ambulatory peritoneal dialysis; 170 patients will be randomized (1:1) to receive XyloCore^® or to continue their pre-randomization peritoneal dialysis (PD) therapy with glucose-only PD solutions, for 6 months. The primary study's objective is to demonstrate the noninferiority of XyloCore^® in terms of Kt/V urea, for which a clinically acceptable noninferiority margin of −0.25 has been determined, assuming that all patients will be treated aiming to a minimum target of 1.7 and an optimal target of 2.0.

Originalsprog	Engelsk
Tidsskrift	Peritoneal Dialysis International
Antal sider	9
ISSN	0896-8608
DOI	https://doi.org/10.1177/08968608241274106
Status	E-pub ahead of print - 2024

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10.1177/08968608241274106

2024 ELIXIR rationale

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Bonomini, M., Davies, S., Kleophas, W., Lambie, M., Reboldi, G., De Liberato, L., Divino-Filho, J. C., Heimburger, O., Ortiz, A., Povlsen, J., Lacobelli, M., Prosdocimi, T., & Arduini, A. (2024). Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis. Peritoneal Dialysis International. Advance online publication. https://doi.org/10.1177/08968608241274106

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title = "Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis",

abstract = "Peritoneal dialysis adoption and technique survival is affected by limitations related to peritoneal membrane longevity and metabolic alterations. Indeed, almost all peritoneal dialysis fluids exploit glucose as an osmotic agent that rapidly diffuses across the peritoneal membrane, potentially resulting in metabolic abnormalities such as hyperglycemia, hyperinsulinemia, obesity, and hyperlipidemia. Moreover, glucose-degradation products generated during heat sterilization, other than glucose itself, induce significant morphological and functional changes in the peritoneum leading to ultrafiltration failure. The partial substitution of glucose with osmotic agents characterized by a better local and systemic biocompatibility has been suggested as a potential strategy to innovate peritoneal dialysis fluids. The approach aims to minimize glucose-associated toxicity, preserving the peritoneal membrane welfare and counteracting common comorbidities. In this work, we report the clinical trial design of ELIXIR, a phase III randomized, controlled, blinded outcome assessment study comparing Xylocore{\textregistered}, an innovative formulation based on Xylitol and l-carnitine, to standard glucose-based regimens, in end-stage kidney disease patients treated with continuous ambulatory peritoneal dialysis; 170 patients will be randomized (1:1) to receive XyloCore{\textregistered} or to continue their pre-randomization peritoneal dialysis (PD) therapy with glucose-only PD solutions, for 6 months. The primary study's objective is to demonstrate the noninferiority of XyloCore{\textregistered} in terms of Kt/V urea, for which a clinically acceptable noninferiority margin of −0.25 has been determined, assuming that all patients will be treated aiming to a minimum target of 1.7 and an optimal target of 2.0.",

keywords = "End-stage kidney disease, dialysis, glucose-sparing, kidney failure-solution, l-carnitine, peritoneal dialysis, xylitol",

author = "Mario Bonomini and Simon Davies and Werner Kleophas and Mark Lambie and Gianpaolo Reboldi and {De Liberato}, Lorenzo and Divino-Filho, {Jos{\'e} Carolino} and Olof Heimburger and Alberto Ortiz and Johan Povlsen and Massimo Lacobelli and Tommaso Prosdocimi and Arduino Arduini",

year = "2024",

doi = "10.1177/08968608241274106",

language = "English",

journal = "Peritoneal Dialysis International",

issn = "0896-8608",

publisher = "Multimed, Inc.",

}

Bonomini, M, Davies, S, Kleophas, W, Lambie, M, Reboldi, G, De Liberato, L, Divino-Filho, JC, Heimburger, O, Ortiz, A, Povlsen, J, Lacobelli, M, Prosdocimi, T & Arduini, A 2024, 'Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis', Peritoneal Dialysis International. https://doi.org/10.1177/08968608241274106

Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis. / Bonomini, Mario; Davies, Simon; Kleophas, Werner et al.
I: Peritoneal Dialysis International, 2024.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis

AU - Bonomini, Mario

AU - Davies, Simon

AU - Kleophas, Werner

AU - Lambie, Mark

AU - Reboldi, Gianpaolo

AU - De Liberato, Lorenzo

AU - Divino-Filho, José Carolino

AU - Heimburger, Olof

AU - Ortiz, Alberto

AU - Povlsen, Johan

AU - Lacobelli, Massimo

AU - Prosdocimi, Tommaso

AU - Arduini, Arduino

PY - 2024

Y1 - 2024

N2 - Peritoneal dialysis adoption and technique survival is affected by limitations related to peritoneal membrane longevity and metabolic alterations. Indeed, almost all peritoneal dialysis fluids exploit glucose as an osmotic agent that rapidly diffuses across the peritoneal membrane, potentially resulting in metabolic abnormalities such as hyperglycemia, hyperinsulinemia, obesity, and hyperlipidemia. Moreover, glucose-degradation products generated during heat sterilization, other than glucose itself, induce significant morphological and functional changes in the peritoneum leading to ultrafiltration failure. The partial substitution of glucose with osmotic agents characterized by a better local and systemic biocompatibility has been suggested as a potential strategy to innovate peritoneal dialysis fluids. The approach aims to minimize glucose-associated toxicity, preserving the peritoneal membrane welfare and counteracting common comorbidities. In this work, we report the clinical trial design of ELIXIR, a phase III randomized, controlled, blinded outcome assessment study comparing Xylocore®, an innovative formulation based on Xylitol and l-carnitine, to standard glucose-based regimens, in end-stage kidney disease patients treated with continuous ambulatory peritoneal dialysis; 170 patients will be randomized (1:1) to receive XyloCore® or to continue their pre-randomization peritoneal dialysis (PD) therapy with glucose-only PD solutions, for 6 months. The primary study's objective is to demonstrate the noninferiority of XyloCore® in terms of Kt/V urea, for which a clinically acceptable noninferiority margin of −0.25 has been determined, assuming that all patients will be treated aiming to a minimum target of 1.7 and an optimal target of 2.0.

AB - Peritoneal dialysis adoption and technique survival is affected by limitations related to peritoneal membrane longevity and metabolic alterations. Indeed, almost all peritoneal dialysis fluids exploit glucose as an osmotic agent that rapidly diffuses across the peritoneal membrane, potentially resulting in metabolic abnormalities such as hyperglycemia, hyperinsulinemia, obesity, and hyperlipidemia. Moreover, glucose-degradation products generated during heat sterilization, other than glucose itself, induce significant morphological and functional changes in the peritoneum leading to ultrafiltration failure. The partial substitution of glucose with osmotic agents characterized by a better local and systemic biocompatibility has been suggested as a potential strategy to innovate peritoneal dialysis fluids. The approach aims to minimize glucose-associated toxicity, preserving the peritoneal membrane welfare and counteracting common comorbidities. In this work, we report the clinical trial design of ELIXIR, a phase III randomized, controlled, blinded outcome assessment study comparing Xylocore®, an innovative formulation based on Xylitol and l-carnitine, to standard glucose-based regimens, in end-stage kidney disease patients treated with continuous ambulatory peritoneal dialysis; 170 patients will be randomized (1:1) to receive XyloCore® or to continue their pre-randomization peritoneal dialysis (PD) therapy with glucose-only PD solutions, for 6 months. The primary study's objective is to demonstrate the noninferiority of XyloCore® in terms of Kt/V urea, for which a clinically acceptable noninferiority margin of −0.25 has been determined, assuming that all patients will be treated aiming to a minimum target of 1.7 and an optimal target of 2.0.

KW - End-stage kidney disease

KW - dialysis

KW - glucose-sparing

KW - kidney failure-solution

KW - l-carnitine

KW - peritoneal dialysis

KW - xylitol

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U2 - 10.1177/08968608241274106

DO - 10.1177/08968608241274106

M3 - Journal article

SN - 0896-8608

JO - Peritoneal Dialysis International

JF - Peritoneal Dialysis International

ER -

Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis

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