Theranova Randomized, Controlled, Trial (RCT) in China

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

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).

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Failure; Chronic Kidney Failure
• Intervention / Treatment: Device: Theranova 400 Dialyzer; Device: FX 800 Dialyzer

• Study Type: Interventional
• Enrollment (Anticipated): 272
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100034
    • Recruiting
    • Baxter Investigational SIte
  • Beijing, China, 100013
    • Recruiting
    • Baxter Investigational SIte
  • Dalian, China, 116001
    • Recruiting
    • Baxter Investigational SIte
  • Dalian, China, 116011
    • Recruiting
    • Baxter Investigational SIte
    • Contact: Baxter I Site
  • Hangzhou, China, 310014
    • Recruiting
    • Baxter Investigational SIte
  • Nanjing, China, 210002
    • Recruiting
    • Baxter Investigational SIte
  • Shanghai, China, 200011
    • Recruiting
    • Baxter Investigational SIte
  • Shanghai, China, 200127
    • Recruiting
    • Baxter Investigational SIte
  • Shenzhen, China, 518020
    • Recruiting
    • Baxter Investigational SIte
  • Suzhou, China, 215006
    • Recruiting
    • Baxter Investigational SIte

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:

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.

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: Theranova 400 Dialyzer; 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; Dialysis performed in HD mode.; Other Names: Hollow fiber dialyzers with medium cut-off membrane
Active Comparator: FX 800 Dialyzer; 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; Dialysis performed in HDF mode.; Other Names: Hollow fiber hemodialysis filter

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Baxter Healthcare Corporation

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: BXU561424

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sharing of Clinical Trial Data: Baxter is committed to sharing clinical trial data with external medical experts and scientific researchers in the interest of advancing public health. As such, Baxter will supply anonymized Individual Patient Datasets (IPD) and supporting documents (synopsis of clinical study reports, protocol and SAP's)
• IPD Sharing Time Frame: Upon approval of a legitimate research request.
• IPD Sharing Access Criteria: Research requests will be reviewed by qualified medical and scientific experts within the company. If Baxter agrees to the release of clinical data for research purposes, the requestor will be required to sign a data sharing agreement (DSA) in order to ensure protection of patient confidentiality and any intellectual property rights of Baxter prior to the release of any data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

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