Acute Kidney Failure, Chronic Kidney Failure
Conditions
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).
Interventions
DEVICETheranova 400 Dialyzer
Dialysis performed in HD mode.
DEVICEFX 800 Dialyzer
Dialysis performed in HDF mode.
Sponsors
Baxter Healthcare Corporation
Vantive Health LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction Ratio (RR) of Lambda Free Light Chains (λ FLC) | Assessed at the mid-week treatment day dialysis session | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis. The RR was calculated using the following formula: \[(Cpre-Cpost)/Cpre\], where Cpre and Cpost were the arterial plasma concentrations of λ FLC measured pre- and post- the mid-week dialysis session, respectively |
| Reduction Ratio of Beta-2 Microglobulin (β2-MG) | Assessed at the mid-week treatment day dialysis session | One mid-week treatment day dialysis session, pre-dialysis and post-dialysis. The RR was calculated using the following formula: \[(Cpre-Cpost)/Cpre\], where Cpre and Cpost were the arterial plasma β2-MG concentrations measured pre- and post- the mid-week dialysis session, respectively. |
Countries
China
Participant flow
Recruitment details
Patients were recruited across 11 investigational sites in China, between June 2022 and July 2023.
Pre-assignment details
Of the 323 patients enrolled, 274 patients met the study entry criteria and were randomized for treatment.
Participants by arm
| Arm | Count |
|---|---|
| Theranova 400 Dialyzer 1 week, 1 mid-week HD therapy session.
Theranova 400 Dialyzer: Dialysis performed in HD mode. | 138 |
| FX 800 Dialyzer 1 week, 1 mid-week HDF therapy session.
FX 800 Dialyzer: Dialysis performed in HDF mode. | 136 |
| Total | 274 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Theranova 400 Dialyzer | FX 800 Dialyzer | Total |
|---|---|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 11.99 | 53.0 years STANDARD_DEVIATION 11.43 | 52.6 years STANDARD_DEVIATION 11.7 |
| BMI | 23.02 kg/m^2 STANDARD_DEVIATION 3.17 | 23.20 kg/m^2 STANDARD_DEVIATION 3.19 | 23.11 kg/m^2 STANDARD_DEVIATION 3.17 |
| Child-bearing potential No | 29 Participants | 23 Participants | 52 Participants |
| Child-bearing potential Yes | 15 Participants | 12 Participants | 27 Participants |
| Dialysis Vintage | 7.17 years STANDARD_DEVIATION 4.86 | 6.28 years STANDARD_DEVIATION 4.45 | 6.73 years STANDARD_DEVIATION 4.67 |
| Dry Weight | 62.47 kg STANDARD_DEVIATION 10.39 | 63.97 kg STANDARD_DEVIATION 10.97 | 63.22 kg STANDARD_DEVIATION 10.69 |
| Height | 167.86 cm STANDARD_DEVIATION 7.28 | 168.92 cm STANDARD_DEVIATION 7.58 | 168.39 cm STANDARD_DEVIATION 7.44 |
| Race/Ethnicity, Customized Ethnicity Chinese | 138 Participants | 135 Participants | 273 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 44 Participants | 35 Participants | 79 Participants |
| Sex: Female, Male Male | 94 Participants | 101 Participants | 195 Participants |
| Weight | 65.00 kg STANDARD_DEVIATION 10.62 | 66.39 kg STANDARD_DEVIATION 11.15 | 65.69 kg STANDARD_DEVIATION 10.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 139 | 0 / 135 |
| other Total, other adverse events | 0 / 139 | 0 / 135 |
| serious Total, serious adverse events | 1 / 139 | 0 / 135 |
Outcome results
Primary
Reduction Ratio of Beta-2 Microglobulin (β2-MG)
One mid-week treatment day dialysis session, pre-dialysis and post-dialysis. The RR was calculated using the following formula: \[(Cpre-Cpost)/Cpre\], where Cpre and Cpost were the arterial plasma β2-MG concentrations measured pre- and post- the mid-week dialysis session, respectively.
Time frame: Assessed at the mid-week treatment day dialysis session
Population: The per-protocol set (PPS) was a subset of patients who were randomized to the respective treatment at the mid-week treatment day dialysis session and did not have any major protocol deviations that could affect the assessment of the primary endpoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Theranova 400 Dialyzer | Reduction Ratio of Beta-2 Microglobulin (β2-MG) | 77.03 Reduction Ratio (%) |
| FX 800 Dialyzer | Reduction Ratio of Beta-2 Microglobulin (β2-MG) | 78.22 Reduction Ratio (%) |
Comparison: Non-inferiority of the Theranova 400 Dialyzer compared to the FX 800 Dialyzer in regard to the β2-MG RR at the mid-week treatment day dialysis session was assessed.p-value: <0.000195% CI: [-2.54, 0.16]t-test, 2 sided
Primary
Reduction Ratio (RR) of Lambda Free Light Chains (λ FLC)
One mid-week treatment day dialysis session, pre-dialysis and post-dialysis. The RR was calculated using the following formula: \[(Cpre-Cpost)/Cpre\], where Cpre and Cpost were the arterial plasma concentrations of λ FLC measured pre- and post- the mid-week dialysis session, respectively
Time frame: Assessed at the mid-week treatment day dialysis session
Population: The per-protocol set (PPS) is a subset of patients who were randomized to the respective treatment at the mid-week treatment day dialysis session and did not have any major protocol deviations that could affect the assessment of the primary endpoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Theranova 400 Dialyzer | Reduction Ratio (RR) of Lambda Free Light Chains (λ FLC) | 36.02 Reduction Ratio (%) |
| FX 800 Dialyzer | Reduction Ratio (RR) of Lambda Free Light Chains (λ FLC) | 19.03 Reduction Ratio (%) |
Comparison: Non-inferiority of the Theranova 400 Dialyzer compared to the FX 800 Dialyzer in regard to the λ FLC RR at the mid-week treatment day dialysis session was assessed.p-value: <0.000195% CI: [14.84, 19.15]t-test, 2 sided