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

• ClinicalTrials.gov Identifier: NCT03499691
• Recruitment Status: Completed
• First Posted: April 17, 2018
• Last Update Posted: November 9, 2018
• Sponsor: Baxter Healthcare Corporation
• Information provided by (Responsible Party): Baxter Healthcare Corporation

Tracking Information

• First Submitted Date: April 9, 2018
• First Posted Date: April 17, 2018
• Last Update Posted Date: November 9, 2018
• Actual Study Start Date: April 11, 2018
• Actual Primary Completion Date: October 4, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 13, 2018)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 13, 2018)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Exploratory Study to Explore the Safety and Efficacy of the HDx Therapy Using Theranova 500 Dialyzer in Comparison to Hemodiafiltration
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: End Stage Renal Disease

Intervention

• 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.
• 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.

Study Arms

• Experimental: Expanded Hemodialysis (HDx) Therapy
  Patients will undergo 3 dialysis sessions per week with Theranova 500 for up to 24 weeks.
  Intervention: Device: Theranova 500 medium cut-off dialyzer
• Active Comparator: Hemodiafiltration (HDF) Therapy
  Patients will undergo 3 dialysis sessions per week with on-line HDF for up to 24 weeks.
  Intervention: Device: Hemodiafiltration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 25, 2018): 43
• Original Estimated Enrollment (submitted: April 13, 2018): 40
• Actual Study Completion Date: October 4, 2018
• Actual Primary Completion Date: October 4, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT03499691
• Other Study ID Numbers: BXU012191
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Baxter Healthcare Corporation
• Study Sponsor: Baxter Healthcare Corporation
• Collaborators: Not Provided

Investigators

• Study Director: Baxter Clinical Trials; Baxter Healthcare

• PRS Account: Baxter Healthcare Corporation
• Verification Date: November 2018