Efficacy of pHA130 Hemoadsorption for 4 Hours (p4H Study)

Peking University People's Hospital34 enrolled

Overview

This is an open-label, randomized, crossover study to evaluate the efficacy of extending the duration of hemoadsorption (HA) combined with hemodialysis (HD) from 2 hours to 4 hours for clearing protein-bound uremic toxins, such as Indoxyl Sulfate (IS), in stable maintenance hemodialysis patients. Patients will be randomized to receive either 2-hour HA or 4-hour HA once a week for 8 weeks, then cross over to the other treatment for another 8 weeks after a 2-week washout period. The primary endpoint is the reduction rate of IS.

Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) have a high burden of uremic toxins, particularly protein-bound uremic toxins (PBUTs), which are poorly cleared by conventional dialysis and are associated with high cardiovascular mortality. hemoadsorption (HA) is an adjunctive blood purification technique effective at removing PBUTs. The standard duration for HA sessions is typically 2-2.5 hours. However, emerging evidence suggests that extending the treatment duration may enhance toxin removal. This study aims to rigorously compare the efficacy and safety of a 4-hour HA session combined with hemodialysis against a standard 2-hour session in clearing key PBUTs like Indoxyl Sulfate (IS) and p-Cresyl Sulfate (PCS). The findings will provide crucial evidence for optimizing HA treatment protocols to improve toxin clearance and potentially patient outcomes in the ESRD population.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

End Stage Renal Disease on Dialysis

Interventions

pHA130 Hemoadsorption + High-Flux HemodialysisDEVICE

A combination blood-purification procedure in which a pHA130 hemoperfusion cartridge is connected in series with a high-flux hemodialyzer. Blood first passes through the HP cartridge to adsorb protein-bound uremic toxins and is then dialyzed. In the 4-hour arm the HP cartridge remains online for the entire 4-hour session; in the 2-hour arm the cartridge is removed after 2 hours and dialysis continues alone for the remaining 2 hours. Blood-flow rates are 250-350 mL/min (4-hour arm) or 200-250 mL/min (2-hour arm).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age between 18 and 75 years, regardless of gender * Stable maintenance hemodialysis for ≥3 months, with a relatively fixed dialysis regimen * Receiving hemodialysis 3 times per week, each session lasting ≥4 hours * Single-pool Kt/V (spKt/V) ≥1.2 within 8 weeks prior to enrollment * Willing and able to sign the informed consent form Exclusion Criteria: * Life expectancy less than 1 year * White blood cell count \< 4 × 10⁹/L and/or platelet count \< 60 × 10⁹/L * Active or chronic gastrointestinal bleeding, or diagnosed coagulation disorders * Active malignant tumor * Active infection * Pregnant or breastfeeding * Participation in another clinical trial within the past month or currently enrolled in one * Deemed unsuitable for the study by the investigator

Outcomes

Primary Outcomes

Reduction Rate of Serum Indoxyl Sulfate (IS)

The reduction rate (RR) of serum Indoxyl Sulfate (IS) after a single HAHD treatment session. The RR is calculated as: RR(%) = (1 - (Post-treatment Concentration / Pre-treatment Concentration)) × 100. Post-treatment concentration will be corrected for hemoconcentration.

Time frame: At Week 1, Week 8, Week 11, and Week 18; blood samples will be collected at 0 hours (before treatment), 2 hours after treatment begins, and 4 hours (end of treatment) during each visit

Secondary Outcomes

Reduction Rate of p-Cresyl Sulfate (PCS)

RR of serum PCS after a single session

Time frame: At Week 1, Week 8, Week 11, and Week 18; blood samples will be collected at 0 hours (before treatment), 2 hours after treatment begins, and 4 hours (end of treatment) during each visit

Change from Baseline in Pre-dialysis IS levels

Change in pre-dialysis serum concentrations of IS from the beginning to the end of each 8-week treatment period

Time frame: Baseline (Week 1) to end of period 1 (Week 8); Baseline of period 2 (Week 11) to end of period 2 (Week 18)

Change from Baseline in Pre-dialysis PCS levels

Change in pre-dialysis serum concentrations of PCS from the beginning to the end of each 8-week treatment period

Time frame: Baseline (Week 1) to end of period 1 (Week 8); Baseline of period 2 (Week 11) to end of period 2 (Week 18)

Clearance of Other Uremic Toxins

Reduction rates and/or clearance of urea, creatinine, β2-microglobulin, C-reactive protein (CRP), and Interleukin-6 (IL-6)

Time frame: Week 1, Week 8, Week 11, Week 18

Number of Participants With Adverse Events, Circuit Coagulation, and Abnormal Changes in Vital Signs or Laboratory Parameters

All adverse events (AEs) reported during the study will be recorded and assessed for severity and relationship to the intervention. Specific safety indicators include the incidence of circuit coagulation, decreases in white blood cell count, platelet count, and hemoglobin levels, as well as changes in vital signs.

Time frame: Throughout the entire study duration (up to 18 weeks)