Clinical trial NCT05309291: Theranova Randomized, Controlled, Trial (RCT) in China
Official title: A Randomized, Open-label, Controlled, Parallel, Multicenter Study in Kidney Failure Patients on Hemodialysis Comparing the Theranova Dialyzer to Hemodiafiltration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Failure
Acute Kidney Failure
Lead sponsor: Vantive Health LLC
Sponsor class: INDUSTRY
Collaborators: name: Baxter Healthcare Corporation
First posted: 2022-04-04
Enrollment: 323
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Traditional hemodialysis (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 can indirectly lead to the death of patients. Studies have shown that, compared to conventional high-flux HD (HF-HD), hemodiafiltration (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 HD mode (hereinafter referred to as Theranova 400) compared to HDF, using FX 800 in HDF mode (hereinafter referred to as FX 800).


Eligibility criteria: Inclusion Criteria:

1. Patients aged ≥18 years old and ≤80 years old, regardless of gender;
2. Patients who are able to sign informed consent form (ICF) after an explanation of the proposed study;
3. Patients who receive in-center HD treatment at a site that routinely implements high flux dialysis and HDF;
4. Patients who have been stable receiving in-center HD/HDF for \>3 months prior to study enrollment;
5. 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;
6. 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;
7. 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;
8. Patients with a minimum total convective volume (including ultrafiltration (UF)) of 16 L post-dilution for the most recent HDF treatment;
9. 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:

1. Patients who have acute kidney injury with the chance for recovery;
2. Pregnant and lactating women;
3. 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;
4. Patients with known hemodynamic instability, anemia (hemoglobin \<90 g/L), and/or patients with hemoglobin \>130g/L for coagulation risk;
5. Patients with active or ongoing infection as per investigator's judgement (e.g C-reactive protein \[CRP\] level more than 5 folds of normal);
6. Patients who are severely malnourished or with significant disease that interferes with liver synthetic function ( e.g. with serum albumin \<30 g/L);
7. 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;
8. Patients with positive serology tests for human immunodeficiency virus (HIV), Syphilis;
9. Patients receiving immunosuppressive treatment or with autoimmune disease;
10. 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;
11. 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;
12. 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;
13. Patients with a history of severe mental disorders who are unable to provide consent or comply with study procedures as assessed by the investigator;
14. Patients who are currently participating in or have previously participated in other interventional clinical studies during the past 30 days;
15. Patients with any comorbidity possibly conflicting with the study as judged by the investigator.

Primary outcomes:
measure: Reduction Ratio (RR) of Lambda Free Light Chains (λ FLC)
timeFrame: Assessed at the mid-week treatment day dialysis session
measure: Reduction Ratio of Beta-2 Microglobulin (β2-MG)
timeFrame: Assessed at the mid-week treatment day dialysis session
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Investigational Site
city: Beijing
country: China
facility: Investigational Site
city: Dalian
country: China
facility: Investigational Site
city: Dalian
country: China
facility: Investigational Site
city: Hangzhou
country: China
facility: Investigational Site
city: Nanjing
country: China
facility: Investigational Site
city: Shanghai
country: China
facility: Investigational Site
city: Shanghai
country: China
facility: Investigational Site
city: Shenzhen
country: China
facility: Investigational Site
city: Suzhou
country: China
facility: Investigational Site
Study officials:
References: