Randomized Cross-Over Comparison of Medium Cut-Off and High-Flux Hemodialysis Membranes

Official title

Randomized Cross-Over Evaluation of Medium Cut-Off and High-Flux Hemodialysis Membranes on Inflammation and Cardiovascular Function in Maintenance Hemodialysis Patients

Overview

Patients receiving maintenance hemodialysis are at increased risk of cardiovascular disease, chronic inflammation, endothelial dysfunction, and impaired quality of life. Medium cut-Off (MCO) hemodialysis membranes have been developed to enhance the removal of middle-molecular-weight uremic toxins compared with conventional high-flux membranes, which may improve inflammatory status and cardiovascular health. The aim of this study is to compare the effects of MCO and high-flux hemodialysis membranes on inflammatory biomarkers and cardiovascular function in adult patients receiving maintenance hemodialysis. The primary outcomes are changes in serum interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1) levels. Secondary outcomes include arterial stiffness assessed by pulse wave velocity (PWV), body composition assessed by Body Composition Monitor (BCM), handgrip strength, and patient-reported outcomes including quality of life, pruritus, and pain scores. This is a prospective, randomized, open-label, two-sequence, two-period crossover study conducted at Gazi University Faculty of Medicine. Thirty adult hemodialysis patients will be randomized to one of two treatment sequences. Participants in Sequence A will receive MCO dialysis membranes for the first 3 months followed by high-flux membranes for the next 3 months. Participants in Sequence B will receive high-flux membranes for the first 3 months followed by MCO membranes for the next 3 months. Blood samples and clinical assessments will be performed at baseline, month 3, and month 6. The study is expected to provide evidence regarding the effects of different dialysis membrane technologies on inflammation and cardiovascular health and may contribute to optimizing membrane selection in routine hemodialysis practice.

Detailed description

Cardiovascular disease remains the leading cause of morbidity and mortality in patients receiving maintenance hemodialysis. Chronic inflammation, endothelial dysfunction, vascular stiffness, and the accumulation of middle-molecular-weight uremic toxins are considered important contributors to adverse cardiovascular outcomes in this population. Conventional high-flux hemodialysis membranes provide effective small-solute clearance but have limited capacity for removing larger middle molecules involved in inflammation and vascular injury.

Medium cut-off (MCO) membranes have been developed to enhance the clearance of larger middle molecules while maintaining albumin retention within acceptable limits. Previous studies have suggested that MCO membranes may improve inflammatory profiles and patient-centered outcomes; however, data regarding their effects on endothelial dysfunction, arterial stiffness, body composition, and patient-reported outcomes remain limited.

This study is designed as a prospective, randomized, open-label, two-sequence, two-period crossover clinical investigation comparing MCO and high-flux hemodialysis membranes in maintenance hemodialysis patients. Participants will be randomized in a 1:1 ratio to one of two treatment sequences. Sequence A will receive MCO membranes during Period 1 (Months 0-3) followed by high-flux membranes during Period 2 (Months 3-6). Sequence B will receive high-flux membranes during Period 1 followed by MCO membranes during Period 2. This crossover design allows each participant to serve as his or her own control, thereby reducing inter-individual variability.

Study assessments will be performed at baseline, Month 3, and Month 6. In addition to routine laboratory testing performed during standard hemodialysis follow-up, blood samples will be obtained at baseline, Month 3, and Month 6 for the measurement of serum interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1). Cardiovascular assessment will include pulse wave velocity (PWV) measurement. Nutritional and body composition status will be evaluated using Body Composition Monitor (BCM) parameters, including overhydration, ECW/TBW ratio, intracellular water, lean tissue index, body cell mass, and phase angle. Functional status will be assessed by handgrip strength measurement. Patient-reported outcomes will be evaluated using the Kidney Disease Quality of Life-36 (KDQOL-36), UP-Dial pruritus questionnaire, and Short-Form McGill Pain Questionnaire (SF-MPQ).

The primary objective is to compare the effects of MCO and high-flux membranes on IL-6 and VCAM-1 levels. Secondary objectives include evaluation of arterial stiffness, body composition, physical function, and patient-reported outcomes. The findings may provide clinically relevant evidence regarding membrane selection strategies in routine hemodialysis practice.

Interventions

• Device Medium Cut-Off Hemodialysis Membrane
  Medium cut-off (MCO) hemodialysis membrane used as part of routine maintenance hemodialysis treatment. MCO membranes are designed to enhance the clearance of larger middle-molecular-weight uremic toxins while maintaining clinically acceptable albumin retention. Participants assigned to MCO treatment periods will receive thrice-weekly hemodialysis according to standard clinical practice. In this study, MCO treatment will be delivered using the ELISIO™ MCO series (Nipro).
• Device High-Flux Hemodialysis Membrane
  High-flux hemodialysis membrane used as part of routine maintenance hemodialysis treatment. High-flux membranes represent the current standard dialysis technology and provide effective clearance of small solutes and selected middle molecules. Participants assigned to high-flux treatment periods will receive thrice-weekly hemodialysis according to standard clinical practice. In this study, high-flux treatment will be delivered using the ELISIO™ HF series (Nipro).

Primary outcome measures

• Change in Serum Interleukin-6 (IL-6) [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]

Secondary outcome measures (10)

• Change in Pulse Wave Velocity (PWV) [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in Handgrip Strength [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in Kidney Disease Quality of Life-36 (KDQOL-36) Score [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in UP-Dial Pruritus Score [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in Short-Form McGill Pain Questionnaire (SF-MPQ) Score [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in Overhydration (OH) [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in Extracellular Water to Total Body Water Ratio (ECW/TBW) [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in Intracellular Water (ICW) [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in Lean Tissue Index (LTI) [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]
• Change in Body Cell Mass (BCM) [Time frame: At baseline (July 2026), Month 3 (October 2026), and Month 6 (January 2027)]

Eligibility criteria

Inclusion criteria

• Age 18 to 80 years.
• Receiving maintenance hemodialysis for at least 6 months.
• Clinically stable and receiving thrice-weekly hemodialysis.
• Able to comply with study procedures, questionnaires, and scheduled assessments.
• Able and willing to provide written informed consent.

Exclusion criteria

• Acute infection at screening or enrollment.
• Major surgery within the previous 3 months.
• Active malignancy requiring ongoing treatment.
• Terminal illness with limited life expectancy.
• Physical or cognitive impairment preventing completion of study procedures or questionnaires.
• Inability or unwillingness to provide written informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

Turkey (Türkiye) · 1 center

• Gazi University Faculty of Medicine, Department of Nephrology, Hemodialysis Unit — Ankara

Publications

• Yang J, Ke G, Liao Y, Guo Y, Gao X. Efficacy of medium cut-off dialyzers and comparison with high-flux dialyzers in patients on maintenance hemodialysis: A systematic review and meta-analysis. Ther Apher Dial. 2022 Aug;26(4):756-768. doi: 10.1111/1744-9987.13755. Epub 2021 Dec 4. PMID 34773675
• Zickler D, Schindler R, Willy K, Martus P, Pawlak M, Storr M, Hulko M, Boehler T, Glomb MA, Liehr K, Henning C, Templin M, Trojanowicz B, Ulrich C, Werner K, Fiedler R, Girndt M. Medium Cut-Off (MCO) Membranes Reduce Inflammation in Chronic Dialysis Patients-A Randomized Controlled Clinical Trial. PLoS One. 2017 Jan 13;12(1):e0169024. doi: 10.1371/journal.pone.0169024. eCollection 2017. PMID 28085888
• Kirsch AH, Lyko R, Nilsson LG, Beck W, Amdahl M, Lechner P, Schneider A, Wanner C, Rosenkranz AR, Krieter DH. Performance of hemodialysis with novel medium cut-off dialyzers. Nephrol Dial Transplant. 2017 Jan 1;32(1):165-172. doi: 10.1093/ndt/gfw310. PMID 27587605

Identifiers

NCT: NCT07679763 · GAZI-HD-MCO-HF-2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗