Clinical trial NCT06552546: Pharmacokinetics of Single- and Double-dose Icodextrin
Official title: Pharmacokinetics of Single- and Double-dose Icodextrin in Patients on Peritoneal Dialysis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Peritoneal Dialysis
Keywords: Icodextrin
Pharmacokinetics
Peritoneal dialysis
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2024-08-14
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Peak concentration (Cmax)
timeFrame: SICO: 0, 4, 8, 10, 12,16, 20, 24, 48, 72 hour, and day 7 and 14; DICO: 0, 4, 8, 12,16, 18, 20, 24, 28, 32, 56, 80 hour and day 7 and 14
measure: Peak time (Tmax)
timeFrame: SICO: 0, 4, 8, 10, 12,16, 20, 24, 48, 72 hour, and day 7 and 14; DICO: 0, 4, 8, 12,16, 18, 20, 24, 28, 32, 56, 80 hour and day 7 and 14
measure: Area under the concentration-time curve（AUC）
timeFrame: 14 days
measure: Elimination half life（t1/2）
timeFrame: 14 days
measure: Clearance(CL)
timeFrame: 14 days
Secondary outcomes:
measure: Adverse Events
timeFrame: 14 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Jie Dong, Professor
role: PRINCIPAL_INVESTIGATOR
References: