Ultrafiltration Efficacy of a PD Solution Containing Icodextrin-Xylitol-Carnitine

Ultrafiltration Efficacy of a PD Solution Containing Icodextrin-Xylitol-Carnitine Compared to Icodextrin Alone, an Exploratory Study.

Randomized, cross-over, controlled, open label study. The aim of this study is to demonstrate that glucose may completely be replaced by a combination of xylitol and carnitine in the bimodal PD solution for long dwell exchange.

Study Overview

• Status: Withdrawn
• Conditions: End Stage Renal Disease (ESRD)
• Intervention / Treatment: Drug: Icodextrin, xylitol and carnitine solution for peritoneal dialysis; Drug: EXTRANEAL 7.5G/100Ml Peritoneal Dialysis Solution

Detailed Description

The use of a solution icodextrin, xylitol and carnitine (IXC) as the osmotic agent in dialysate for the long dwell exchange provides sustained ultrafiltration (UF) through colloid osmosis, allowing a consistent reduction in extracellular fluid volume without the expected fall in urine output. The other major advantage of IXC is the reduced exposure and absorption of glucose as the main osmotic agent in PD therapy. The aim of this study is to demonstrate that glucose may completely be replaced by a combination of xylitol and carnitine in the bimodal IXC-based PD solution. Compared to glucose, indeed, carnitine and xylitol are extremely stable naturally occurring compounds, even at temperatures higher than those used to steam-sterilize infusional product. As a consequence, xylitol and carnitine may represent better alternatives than glucose as an osmotic ingredient both from the manufacturing and biocompatibility standpoints. Moreover, xylitol and carnitine have an excellent safety profile and possess distinct systemic actions, which are more favorable than glucose.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years
• Diagnosis of ESRD and have been on Continuous Ambulatory Peritoneal Dialysis (CAPD) or Automated Peritoneal Dialysis (APD) for at least 3 months
• A stable clinical condition during the two weeks immediately prior to randomization
• Blood hemoglobin concentration above 8,5 g/100ml
• Has not experienced peritonitis episodes in the last 3 months
• Treated with Extraneal for at least 1 month
• Peritoneal Equilibration Test (PET) performed in the last three months
• Has understood and signed the Informed Consent Form.

Exclusion Criteria:

• History of drug or alcohol abuse in the six months prior to entering the protocol
• Acute infectious condition
• History of severe congestive heart failure and clinically significant arrhythmia
• Malignancy within the past 5 years, including lymphoproliferative disorders
• A medical condition that, in the judgment of the Investigator, would jeopardize the patient's safety following exposure to study drug
• A clinically relevant under-hydration as judged by the treating physician
• History of L-Carnitine therapy or use in the month before entering the study
• Received any investigational drug in the 3 months before entering the study
• Pregnancy, lactation, fertility age without protection against pregnancy by adequate contraceptive measures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IXC Peritoneal dialysis solution; IXC (Icodextrin, Xylitol and L-Carnitine) Peritoneal dialysis solution	Drug: Icodextrin, xylitol and carnitine solution for peritoneal dialysis; Patients will receive a long dwell exchange for three days.; Other Names: IXC
Active Comparator: Icodextrin; Extraneal® (7.5% Icodextrin) Peritoneal dialysis solution	Drug: EXTRANEAL 7.5G/100Ml Peritoneal Dialysis Solution; Patients will receive a long dwell exchange for three days.; Other Names: icodextrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net-ultrafiltration	Net Ultrafiltration at 10 hours (duration of long dwell), in mL, is defined as the difference between the weight of drained volume and weight of the effluent (fill volume).	Changes from baseline value at the end of each product administration period (3 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sodium removal	Net sodium removal will be calculated as the difference between the total amount of sodium drained at end of long dwell (10 hours) and its measure value in the dialysate at time 0 before the initial infusion. Sodium will determined by the hospital laboratory.	Calculated every day for 3 days during each product administration period.
Carnitine plasmatic level	Carnitine plasmatic level is assessed by chemical analysis of patient's plasma samples.	Every day for 3 days during each product administration and during the wash-out period
Xylitol plasmatic level	Xylitol plasmatic leve is assessed by chemical analysis of patient's plasma samples.	Every day for 3 days during each product administration and during the wash-out period.
Xylitol absorption	Xilitol absorption is determined by calculating the difference (in grams) between the amount of xylitol (measured by lab analysis) in plasma and the amount of xylitol in the patient's dialysis solution administered.	Every day for 3 days during each product administration
Adverse Events		Through study completion, an average of 21 days.

Collaborators and Investigators

• Sponsor: Iperboreal Pharma Srl
• Investigators: Principal Investigator: Mario Bonomini, MD, Institute of Nephrology, University of Chieti, Italy

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2019
• Primary Completion (Estimated): December 1, 2022
• Study Completion (Estimated): April 1, 2023

Study Registration Dates

• First Submitted: September 2, 2019
• First Submitted That Met QC Criteria: September 10, 2019
• First Posted (Actual): September 11, 2019

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: March 1, 2022

More Information

Terms related to this study

• 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; Pharmaceutical Solutions; Dialysis Solutions; Icodextrin
• Other Study ID Numbers: IP-001-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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