Pharmacokinetics of Single- and Double-dose Icodextrin

NCT ID: NCT06552546

Last Updated: 2024-08-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-15
• Study Completion Date: 2025-03-30

Brief Summary

The study aims to provide the pharmacokinetics profiles of single- and double-dose icodextrin in patients on peritoneal dialysis (PD). It may expand the available knowledge of the clinical pharmacology of icodextrin following its intraperitoneal administration and fills the gaps in our understanding of the fate of icodextrin and the metabolic consequences of icodextrin and its metabolites.

Detailed Description

Icodextrin is confirmed safe and effective as an alternative osmotic agent by numerous clinical studies. Due to its high molecular weight, icodextrin exerts its effect to enhance ultrafiltration (UF) during long (10~14 hours) dwells through prolonged colloid osmosis across the peritoneal membrane in PD patients. However, the utilization of icodextrin is currently limited to 1 exchange per day in order to avoid plasma accumulation of maltose or other metabolites. Two icodextrin bags per day has been reported to be safely prolong PD technique survival in patients in whom one icodextrin exchange provides insufficient UF. A detailed evaluation of the pharmacokinetics and elimination of icodextrin and metabolites following a single exchange has been reported. However, characterization of the plasma kinetics, metabolism and elimination of double dose icodextrin is not available yet. Therefore, we design the study to provide the pharmacokinetics profile of single- and double-dose icodextrin in patients on peritoneal dialysis. It may expand the available knowledge of the clinical pharmacology of icodextrin following its intraperitoneal administration and fills the gaps in our understanding of the fate of icodextrin and the metabolic consequences of icodextrin and its metabolites.

Eligible participants were admitted to the hosptial ward and used one icodextrin bag (single-dose icodextrin) or two icodextrin bags (double-dose icodextrin) on the first day, depending on their choice. Each icodextrin solution was left in the peritoneal cavity for a 8-hour dwell. The double-dose icodextrin was administered in a sequential way. After the icodextrin exchange(s), the solution was drained from the peritoneal cavity and the patients resumed dialysis using dextrose dialysate with two or three additional manual exchanges performed for the balance of the 24 hours since the icodextrin dwell was initiated. Patients were discharged and requested to return on days 7 and 14. Blood, urine and dialysate samples are collected at the time-points as required. Icodextrin and metabolites were analyzed and the pharmacokinetics profiles of single- and double-dose icodextrin were provided.

Icodextrin was quantified in plasma, urine and dialysate by exhaustive hydrolysis of all glucose polymers to glucose using the enzyme amyloglucosidase. Free glucose (determined prior to hydrolysis) was subtracted from the result of hydrolysis to obtain the icodextrin concentration. Maltose (DP2), maltotriose (DP3), maltotetraose (DP4) were individually quantified in blood, spent dialysate and urine (for patients with urine output) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Conditions

Peritoneal Dialysis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SICO(single-dose icodextrin)

Eligible participants used one icodextrin bag (single-dose icodextrin, SICO) on the first day. Icodextrin solution was left in the peritoneal cavity for a 8-hour dwell. After the icodextrin exchange, the solution was drained from the peritoneal cavity and the patients resumed dialysis using dextrose dialysate with three additional manual exchanges performed for the balance of the 24 hours since the icodextrin dwell was initiated. Patients were discharged and requested to return on days 7 and 14. Blood, urine and dialysate samples are collected at the time-points as required. Icodextrin and metabolites were analyzed and the pharmacokinetics profiles of single-dose icodextrin were provided.

Group Type: EXPERIMENTAL

Icodextrin

Intervention Type: DRUG

Eligible participants were admitted to the hosptial ward and used one icodextrin bag (single-dose icodextrin) or two icodextrin bags (double-dose icodextrin) on the first day, depending on their choice. Each icodextrin solution was left in the peritoneal cavity for a 8-hour dwell. The double-dose icodextrin was administered in a sequential way. After the icodextrin exchange(s), the solution was drained from the peritoneal cavity and the patients resumed dialysis using dextrose dialysate with two or three additional manual exchanges performed for the balance of the 24 hours since the icodextrin dwell was initiated. Patients were discharged and requested to return on days 7 and 14. Blood, urine and dialysate samples are collected at the time-points as required. Icodextrin and metabolites were analyzed and the pharmacokinetics profiles of single- and double-dose icodextrin were provided.

DICO(double-dose icodextrin)

Eligible participants used two icodextrin bags (double-dose icodextrin, DICO) on the first day. Each icodextrin solution was left in the peritoneal cavity for a 8-hour dwell. The double-dose icodextrin was administered in a sequential way. After the icodextrin exchange, the solution was drained from the peritoneal cavity and the patients resumed dialysis using dextrose dialysate with three additional manual exchanges performed for the balance of the 24 hours since the icodextrin dwell was initiated. Patients were discharged and requested to return on days 7 and 14. Blood, urine and dialysate samples are collected at the time-points as required. Icodextrin and metabolites were analyzed and the pharmacokinetics profiles of double-dose icodextrin were provided.

Group Type: EXPERIMENTAL

Icodextrin

Intervention Type: DRUG

Eligible participants were admitted to the hosptial ward and used one icodextrin bag (single-dose icodextrin) or two icodextrin bags (double-dose icodextrin) on the first day, depending on their choice. Each icodextrin solution was left in the peritoneal cavity for a 8-hour dwell. The double-dose icodextrin was administered in a sequential way. After the icodextrin exchange(s), the solution was drained from the peritoneal cavity and the patients resumed dialysis using dextrose dialysate with two or three additional manual exchanges performed for the balance of the 24 hours since the icodextrin dwell was initiated. Patients were discharged and requested to return on days 7 and 14. Blood, urine and dialysate samples are collected at the time-points as required. Icodextrin and metabolites were analyzed and the pharmacokinetics profiles of single- and double-dose icodextrin were provided.

Interventions

Icodextrin

Eligible participants were admitted to the hosptial ward and used one icodextrin bag (single-dose icodextrin) or two icodextrin bags (double-dose icodextrin) on the first day, depending on their choice. Each icodextrin solution was left in the peritoneal cavity for a 8-hour dwell. The double-dose icodextrin was administered in a sequential way. After the icodextrin exchange(s), the solution was drained from the peritoneal cavity and the patients resumed dialysis using dextrose dialysate with two or three additional manual exchanges performed for the balance of the 24 hours since the icodextrin dwell was initiated. Patients were discharged and requested to return on days 7 and 14. Blood, urine and dialysate samples are collected at the time-points as required. Icodextrin and metabolites were analyzed and the pharmacokinetics profiles of single- and double-dose icodextrin were provided.

Intervention Type: DRUG

Other Intervention Names

Extraneal®，Baxter Healthcare (Guangzhou) Co., Ltd.， Guangzhou，China

Eligibility Criteria

Inclusion Criteria

• Patients with end stage renal disease, receiving peritoneal dialysis for > 3 months, and clinically stable.
• Suitable for 4 exchanges of manual peritoneal dialysis on the first study day.

Exclusion Criteria

• History of allergic reaction to icodextrin dialysis solution or corn starch;
• With malignant tumor receiving radiotherapy and/or chemotherapy, active hepatitis or hepatic failure, active autoimmune disease, severe digestive malabsorption or an eating disorder, or HIV/AIDS;
• Acute systemic infection, peritonitis, catheter-related infection, cardiovascular disease, surgery, or trauma in the previous one month;
• A high probability of receiving a kidney transplant or transferring to hemodialysis or drop-out due to socioeconomic causes within 1 months;
• Receiving hybrid dialysis (peritoneal dialysis combined with hemodialysis);
• Pregnant or lactating female;
• Having used icodextrin within previous 30 days；
• Peritoneal catheter dysfunction；
• Not suitable for enrollment assessed by researchers, including those unable followed the study protocol, or enrolled in other intervention studies, or with other reasons considering not suitable for enrollment by researchers.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University First Hospital

OTHER

Sponsor Role: lead

Responsible Party

Dong Jie

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jie Dong, Professor

Role: PRINCIPAL_INVESTIGATOR

Peking University First Hospital

Locations

Peking University First Hospital

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Jie Dong, Professor

Role: CONTACT

jie.dong@bjmu.edu.cn

+86-13911841538

Zhikai Yang, Doctor

Role: CONTACT

seapollar@126.com

+86-13671248465

Other Identifiers

2024-524

Identifier Type: -

Identifier Source: org_study_id