Theranova Randomized, Controlled, Trial (RCT) in China

Study Overview
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Brief Summary
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Traditional HD therapy is very effective in clearing urea and smaller middle molecules, but is limited in clearing larger middle molecules. These accumulated large middle-molecular-weight uremic toxins may cause and aggravate inflammation, atherosclerosis and calcification, which indirectly lead to the death of patients. Studies have shown that, compared to conventional high-flux HD (HF-HD), HDF that combines diffusion and convection can reduce the all-cause mortality. Compared to the conventional HF-HD, HDF can more effectively clear larger molecular toxins in one session, which may be related to the better clearance effect of HDF on middle-molecular-weight toxins Theranova's innovative Medium Cut-Off® membranes has high permeability and selectivity to uremic toxins (clearance of a molecular weight of up to 45 kDa) and can retain essential proteins, to maintain patient's albumin level during the HD treatment[9]. Its unique membrane and high cut-off characteristics expand the clearance range beyond those of flux membrane dialyzers. Theranova 400 can be widely used in most blood purification centers under conventional HD equipment and treatment modes, with the effect similar to HDF This study is to demonstrate non-inferiority of the Theranova 400 Dialyzer in hemodialysis (HD) mode (hereinafter referred to as Theranova 400) compared to hemodiafiltration (HDF), using FX 800 in HDF mode (hereinafter referred to as FX 800).

Official Title
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A Randomized, Controlled, Open-label, Parallel, Multicenter Study in Kidney Failure Patients on Hemodialysis Comparing the Theranova Dialyzer to Hemodiafiltration

Conditions
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Chronic Kidney Failure, Acute Kidney Failure

Intervention / Treatment
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* Device: Theranova 400 Dialyzer
* Device: FX 800 Dialyzer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥18 years old and ≤80 years old, regardless of gender; Patients who are able to sign informed consent form (ICF) after an explanation of the proposed study; Patients who receive in-center HD treatment at a site that routinely implements high flux dialysis and HDF; Patients who have been stable receiving in-center HD/HDF for >3 months prior to study enrollment; Patients with kidney failure receiving maintained HD treatment with a history of thrice weekly HD, and at least 1 HDF session within 1 month prior to the study shall be judged by the investigator; Patients who have an adequate arteriovenous (AV) fistula or graft, or dual-lumen tunneled catheter capable of providing a blood flow rate (QB) of at least 250 mL/min; Patients have no changes in dialysis prescription (dialyzer, time, dialysis fluid flow rate (QD), QB, sufficient dialysis anticoagulation, and stable prescribed doses) over last 6 treatments as judged by the investigator. The dialysis treatment time should be 3.5 to 4.5 hours per session with minimum QB of 250 mL/min and QD of 500 mL/min; Patients with a minimum total convective volume (including ultrafiltration (UF)) of 16 L post-dilution for the most recent HDF treatment; Patients who have Kt/Vurea > 1.2 for the last 2 measurements, with the most recent Kt/Vurea measurement taken within 4 weeks before or during study screening. Exclusion Criteria: Patients who have acute kidney injury with the chance for recovery; Pregnant and lactating women; Patients diagnosed with a New York Heart Association (NYHA) Class IV congestive heart failure, or acute coronary syndrome, and/or who have suffered a myocardial infarction within 3 months prior to the start of the study; Patients with known hemodynamic instability, anemia (hemoglobin <90 g/L), and/or patients with hemoglobin >130g/L for coagulation risk; Patients with active or ongoing infection as per investigator's judgement (e.g C-reactive protein [CRP] level more than 5 folds of normal); Patients who are severely malnourished or with significant disease that interferes with liver synthetic function ( e.g. with serum albumin <30 g/L); Patients with positive serology tests for Hepatitis B surface antigen, Hepatitis C total antibody, and advanced liver, or pulmonary disease as judged by the investigator; Patients with positive serology tests for human immunodeficiency virus (HIV), Syphilis; Patients receiving immunosuppressive treatment or with autoimmune disease; Patients with a history of solid tumors requiring anti-cancer therapy in the past or next 6 months, or with a life expectancy of <1 year, or patients with history of hematology neoplasm; Patients who are pre-scheduled for a living donor kidney transplant within the next 1 year, who plan a change to peritoneal dialysis (PD) within the next 1 year, or who require single-needle dialysis therapy; Patients who have had an allergic response to polyarylethersulfone (PAES) or polysulfone (PS) membrane or have history of poor tolerance to dialyzers with synthetic membranes; Patients with a history of severe mental disorders who are unable to provide consent or comply with study procedures as assessed by the investigator; Patients who are currently participating in or have previously participated in other interventional clinical studies during the past 30 days; Patients with any comorbidity possibly conflicting with the study as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Theranova 400 Dialyzer<br>1 week, 1 session in mid-week HD therapy. Pre dialysis blood samples taken from fistula needle or central venous catheter. Post dialysis blood samples taken from arterial sampling port of bloodline | Device: Theranova 400 Dialyzer<br>* Dialysis performed in HD mode.<br>* Other names: Hollow fiber dialyzers with medium cut-off membrane;|
| Active Comparator: FX 800 Dialyzer<br>1 week, 1 session in mid-week HDF therapy. Pre dialysis blood samples taken from fistula needle or central venous catheter. Post dialysis blood samples taken from arterial sampling port of bloodline | Device: FX 800 Dialyzer<br>* Dialysis performed in HDF mode.<br>* Other names: Hollow fiber hemodialysis filter;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction ratio of lambda free light chains (λ FLC) | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis | Up to 1 week | 
| Reduction ratio of beta-2 microglobulin (β2-MG) | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis | Up to 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Kt/V urea | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis | Up to 1 week | 
| Urea Reduction Ratio (URR) | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis | Up to 1 week | 
| Reduction ratio of α1 microglobulin (α1-MG) | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis | Up to 1 week | 
| Reduction ratio of Chitinase-3-like protein (YKL-40) | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis | Up to 1 week | 
| Reduction ratio of complement factor D (CFD) | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis | Up to 1 week | 
| Reduction ratio of myoglobin | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis | Up to 1 week | 
| Reduction ratio of kappa free light chains (κ FLC) | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis | Up to 1 week |