Exploratory Study to Explore the Safety and Efficacy of the HDx Therapy Using Theranova 500 Dialyzer in Comparison to Hemodiafiltration

An Open-label, Prospective, Randomized, Parallel-Group, Exploratory Study to Explore the Safety and Efficacy of the HDx Therapy Using Theranova 500 Dialyzer in Comparison to Hemodiafiltration

Today it is well established that middle molecules comprise several compounds that are not effectively removed by high-flux dialyzers, and effective clearance of large middle molecules in the process of dialysis depends on the dialyzer membrane having large enough pore sizes, larger than the conventional high-flux dialyzers. Studies have found associations between levels of large middle molecule uremic toxins and immune dysfunction and inflammation, as well as adverse outcomes. This indicates that dialysis membranes having larger pores, enabling an expanded HD (HDx) with more effective removal of large middle molecules, can have a positive impact on the inflammatory state. While data is starting to appear on the long-term use of the HDx therapy, little is still known on how large middle molecules and inflammation markers are affected over time.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Device: Theranova 500 medium cut-off dialyzer; Device: Hemodiafiltration

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Murcia, Spain
    • RTS Murcia VII, RTS Servicios de Diálisis S.L.U.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ESRD patients age between 18 - 80 years
• Clinically stable as judged by the treating physician for 30 days prior to enrollment, as demonstrated by pertinent patient medical history, physical examination, and laboratory testing
• Hemodialysis therapy with HDF for at least 3 months immediately prior to study enrollment

Exclusion Criteria:

• No informed consent provided
• Significant psychiatric disorder, mental disability, or other condition that may interfere with the patient's ability to provide informed consent
• Pregnant, breastfeeding, or planning to become pregnant
• Unstable vascular access associated with risk of low and variable extracorporeal blood flow rate (QB)
• Chronic liver disease, known paraprotein-associated disease, known bleeding disorders (e.g., gastrointestinal bleed, colonic polyps, small bowel angiodysplasia and active peptic ulcers)
• Major bleeding episode (i.e. soft tissue bleeding, blood in stool, joint damage, retinal bleeding, extensive mucosal bleeding, exsanguination, cerebral hemorrhage) ≤ 12 weeks prior to enrollment
• Blood (red blood cell) transfusion ≤ 12 weeks prior to enrollment
• Clinical signs of acute infection ≤ 4 weeks prior to enrollment
• Active cancer, except for basal cell or squamous cell skin cancer
• Positive serology test for human immunodeficiency virus or hepatitis infection
• Scheduled for planned interventions requiring hospitalization > 1 week
• Scheduled for living-donor transplantation within the study period
• Currently participating in another interventional clinical study or has participated in another interventional clinical study in the past 3 months that may interfere with this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Expanded Hemodialysis (HDx) Therapy; Patients will undergo 3 dialysis sessions per week with Theranova 500 for up to 24 weeks.	Device: Theranova 500 medium cut-off dialyzer; The patients randomized in this group using the Theranova 500 medium cut-off dialyzer, and blood flow rate and treatment duration will be maintained stable during the observation period. However, other prescriptions will vary based on the Principal Investigator's (PI's) judgment. If other dialyzers need to be temporarily used during the study period it shall be recorded which alternative dialyzers are used and for how long the study patient is on a different dialyzer. However, prior to Week 12 laboratory assessment it is recommended that the patient undergoes three dialysis sessions on the designated treatment mode.
Active Comparator: Hemodiafiltration (HDF) Therapy; Patients will undergo 3 dialysis sessions per week with on-line HDF for up to 24 weeks.	Device: Hemodiafiltration; The patients randomized in this group using the on-line high-flux HDF dialyzer, in post dilution mode, will continue to receive treatments according to their current treatment prescriptions for the duration of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction ratios of lambda immunoglobulin free light chains (λ-FLC)	Week 12
Reduction ratios of kappa immunoglobulin free light chains (k-FLC)	Week 12
Reduction ratios of chitinase-3-like protein 1 (YKL-40)	Week 12
Reduction ratios of fibroblast growth factor 23 (FGF-23)	Week 12
Reduction ratios of serum beta-2 microglobulin (β2M)	Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in mid-week pre-dialysis serum levels of λ-FLC, κ-FLC, YKL-40, FGF-23, ß2M	Week 12 and 24
Change from baseline in mid-week pre-dialysis serum levels of pentraxin-3 (PTX-3), high sensitivity C-reactive protein (hs-CRP), interleukin (IL-6), and interleukin-10 (IL-10)	Week 12 and 24
Percent change from pre- to post-dialysis in mid-week serum levels of hs-CRP	Week 12
Percent change from pre- to post-dialysis in mid-week serum levels of PTX-3	Week 12
Percent change from pre- to post-dialysis in mid-week serum levels of IL-6	Week 12
Percent change from pre- to post-dialysis in mid-week serum levels of IL-10	Week 12
Change from baseline in mid-week pre-dialysis serum level of fibrinogen	Week 12 and 24
Change from baseline in mid-week pre-dialysis serum level of albumin	Week 12 and 24
Single pool Kt/Vurea	Week 24
Serum phosphorous	Week 24
Kidney Disease Quality of Life 36 (KDQOL-36)	Baseline, Week 12, Week 24
Dialysis Symptom Index (DSI)	Baseline, Week 12, Week 24
Serum ferritin	Baseline, Week 12, Week 24
Transferrin Saturation (TSAT)	Baseline, Week 12, Week 24
24-hour urine output on monthly basis	Month 1, Month 2, Month 3, Month 4, Month 5, Month 6
Erythropoiesis stimulating agent (ESA) responsiveness	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Hemoglobin levels	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
ESA dosage by type, administration frequency, and route	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Intravenous iron dosage	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Number of adverse events of hospitalization, cardiovascular events, and infective episodes	Week 1 through Week 24
Total patient death	Week 1 through Week 24

Collaborators and Investigators

• Sponsor: Baxter Healthcare Corporation
• Investigators: Study Director: Baxter Clinical Trials, Baxter Healthcare

Publications and helpful links

General Publications

• Hadad-Arrascue F, Nilsson LG, Rivera AS, Bernardo AA, Cabezuelo Romero JB. Expanded hemodialysis as effective alternative to on-line hemodiafiltration: A randomized mid-term clinical trial. Ther Apher Dial. 2022 Feb;26(1):37-44. doi: 10.1111/1744-9987.13700. Epub 2021 Jun 29.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2018
• Primary Completion (Actual): October 4, 2018
• Study Completion (Actual): October 4, 2018

Study Registration Dates

• First Submitted: April 9, 2018
• First Submitted That Met QC Criteria: April 13, 2018
• First Posted (Actual): April 17, 2018

Study Record Updates

• Last Update Posted (Actual): February 23, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: BXU012191

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No