ESRD (End-Stage Renal Disease), Maintenance Hemodialysis
Conditions
Keywords
Hemoadsorption, Protein-Bound Uremic Toxins, Indoxyl Sulfate, p-Cresyl Sulfate, Cardiovascular Events, Quality of Life
Brief summary
Patients on maintenance hemodialysis (MHD) face a high risk of cardiovascular mortality and reduced quality of life. Conventional high-flux hemodialysis (HD) is the standard of care but has limited efficacy in clearing middle-molecular and protein-bound uremic toxins (PBUTs). The accumulation of these toxins is associated with adverse long-term outcomes. This study evaluates the efficacy and safety of the pHA130 hemoadsorption cartridge, which utilizes a modified resin for enhanced PBUT adsorption, when combined with hemodialysis (HAHD). This is a prospective, open-label, multi-center, randomized controlled trial involving 100 MHD patients. Participants will be randomized 1:1 to either the HAHD group (receiving one HAHD session using the pHA130 cartridge and two standard HD sessions weekly) or the Control group (receiving three standard HD sessions weekly). The primary objective is to assess the reduction in serum indoxyl sulfate (IS) and p-cresol sulfate (PCS) levels from baseline to 12 months. Secondary objectives include evaluating changes in quality of life (KDQoL-SF, MMSE), the progression of coronary artery calcification (CAC), the incidence of major adverse cardiovascular events (MACEs), all-cause mortality, and safety profiles. This trial aims to determine if integrating long-term HAHD therapy can optimize blood purification strategies for the MHD population.
Detailed description
Patients with chronic kidney disease (CKD), particularly those on maintenance hemodialysis (MHD), face a high burden of cardiovascular disease and significantly impaired health-related quality of life. Traditional hemodialysis (HD) and hemodiafiltration (HDF) are effective at clearing small water-soluble molecules, but their efficacy in removing protein-bound uremic toxins (PBUTs)-such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS)-is notably limited. The accumulation of PBUTs is strongly associated with vascular calcification, increased cardiovascular mortality, and severe symptoms like uremic pruritus. Hemoadsorption combined with hemodialysis (HAHD) has emerged as a promising strategy to address this gap. The novel pHA130 hemoadsorption cartridge features a modified resin with micro-controlled positive charges, enhancing its targeted adsorption capacity for PBUTs through electrostatic, hydrophobic, and molecular sieving mechanisms. In vitro studies have shown IS and PCS clearance rates exceeding 90%. The PHOENIX trial is a prospective, open-label, multicenter, randomized controlled trial designed to evaluate the long-term clinical efficacy and safety of the pHA130 cartridge in MHD patients. Following a 4-week run-in period, eligible participants will be randomized 1:1 into two arms: Experimental Group (HAHD): Receives high-flux HD twice a week and HAHD once a week. During HAHD, the pHA130 cartridge is placed in series before the high-flux dialyzer. Control Group (HD): Receives conventional high-flux HD three times a week. The primary endpoint is the percentage reduction in serum IS and PCS concentrations from baseline to 12 months. Secondary endpoints include changes in health-related quality of life (assessed by KDQoL-SF) and cognitive function (assessed by MMSE), progression of coronary artery calcification (CAC) measured by Agatston score, incidence of major adverse cardiovascular events (MACEs), all-cause mortality, and safety metrics. The results of this study aim to provide robust evidence for optimizing blood purification strategies and improving long-term outcomes for patients with end-stage renal disease.
Interventions
DEVICEpHA130 Hemoadsorption Cartridge
Following a 4-week run-in period,patients receive High-flux hemodialysis (HD) twice a week and combined HAHD once a week. During the HAHD session, the pHA130 hemoadsorption cartridge is placed in series with a high-flux dialyzer. Each treatment session lasts for 4 hours.
DEVICEHigh-flux Hemodialyzer
Patients receive conventional high-flux hemodialysis (HD) three times a week. Each treatment session lasts for 4 hours.
Sponsors
China-Japan Friendship Hospital
Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years. * On maintenance hemodialysis for \> 3 months. * Receiving hemodialysis 3 times per week, 4 hours per session. * Standard Kt/V ≥ 1.2. * Voluntarily participates and provides written informed consent.
Exclusion criteria
* Known allergy to the dialyzer or hemoperfusion device. * Platelet count \< 60×10⁹/L. * Serum albumin \< 30 g/L. * 24-hour urine output \> 200 ml. * Inability to achieve a blood flow rate ≥ 200 ml/min. * Coagulation disorders, severe bleeding tendency, or active bleeding. * Pre-dialysis systolic blood pressure \< 90 mmHg or diastolic blood pressure \< 60 mmHg. * Active malignancy. * Active infection, or severe, critical illness of cardiac, pulmonary, hepatic, or nervous systems. * Planned living-donor kidney transplant within the next 6 months. * Current participation in another interventional clinical study, or participation within the past 3 months in an interventional study that may interfere with the present study (e.g., fecal microbiota transplantation); or use of intestinal microecological regulators such as probiotics. * History of unstable angina, myocardial infarction, malignant arrhythmia, cardiac or peripheral vascular surgery, or cerebrovascular accident within the past 8 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction Ratio from baseline in Serum Indoxyl Sulfate (IS) and p-Cresol Sulfate (PCS) Concentration | Baseline, 3, 6, 9, 12 Months | Percentage reduction in serum IS and PCS concentration from baseline after 12 months of treatment, measured by High-Performance Liquid Chromatography (HPLC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Health-Related Quality of Life (HRQoL) | Baseline, 3, 6, 9, 12 Months | Health-Related Quality of Life (HRQoL) is assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF). The KDQOL-SF scores range from a minimum of 0 to a maximum of 100. A higher score indicates a better health-related quality of life. |
| Change from baseline in Cognitive Function | Baseline, 3, 6, 9, 12 Months | Cognitive function is assessed using the Mini-Mental State Examination (MMSE). The MMSE total score ranges from a minimum of 0 to a maximum of 30. A lower score indicates more severe cognitive impairment (i.e., a higher score reflects better cognitive function). |
| Progression of Coronary Artery Calcification (CAC) | Baseline, 6, 12 Months | Coronary Artery Calcification (CAC) progression is assessed by measuring the change in the Agatston score using Computed Tomography (CT) scans. The Agatston score has a minimum value of 0, with no defined maximum upper limit. A higher score indicates a greater burden of coronary artery calcification and a higher cardiovascular risk. |
| All-Cause Mortality | Up to 12 Months | Number of deaths from any cause during the study period. |
| Incidence of Major Adverse Cardiovascular Events (MACEs) | Up to 12 Months | MACEs are defined as a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. |
| Incidence of Adverse Events | Baseline, 3, 6, 9, 12 Months | Safety will be evaluated by monitoring and recording the incidence, severity, and relationship to the intervention of any adverse events (AEs) or serious adverse events (SAEs) throughout the study period. |
Countries
China
Contacts
CONTACTJian Lu, PhD
CONTACTShimin Jiang, PhD
PRINCIPAL_INVESTIGATORWenge Li, MD
China-Japan Friendship Hospital
Outcome results
None listed