Clinical trial NCT03257410: Theranova 400 Dialyzer In End Stage Renal Disease (ESRD) Patients
Official title: A Multi-Center, Prospective, Randomized, Controlled, Open-label, Parallel Study to Evaluate the Safety and Efficacy of the Theranova 400 Dialyzer In End Stage Renal Disease (ESRD) Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Renal Disease
Lead sponsor: Vantive Health LLC
Sponsor class: INDUSTRY
Collaborators: name: Baxter Healthcare Corporation
First posted: 2017-08-22
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study evaluates the efficacy and safety of the Theranova 400 dialyzer compared with Elisio-17 H dialyzer in end stage renal disease patients receiving hemodialysis treatment. Efficacy will be determined by the removal of middle molecules (with different molecular size) from the blood compartment. Safety will be evaluated by maintaining pre-dialysis serum albumin levels and other safety events including laboratory tests and adverse events.

Patients will undergo 3 dialysis sessions per week, for 24 weeks.


Eligibility criteria: Inclusion Criteria:

* ESRD patients age 22 and older, or between ages 18 and 21 with a weight ≥ 40kg.
* Clinically stable as judged by the treating physician and as demonstrated by stable medical history for 30 days prior to enrollment, physical examination, and laboratory testing.
* Hemodialysis therapy with high-flux dialyzers for at least 3 months immediately prior to study enrollment and expected to survive for the next 12 months.
* Expected to maintain an acceptable urea clearance (Kt/V) with a dialyzer of an approximate surface area of 1.7 m2.
* Currently being dialyzed at an in-center setting, on a schedule of 3 times per week.
* Able to give informed consent after an explanation of the proposed study, and who are willing to comply with the study requirements for therapy during the entire study treatment period.
* Have a stable functioning vascular access (arteriovenous fistula, graft, or dual lumen tunneled catheter); stable access will be confirmed by observed Kt/V \>= 1.2 for past 2 measurements, and/or achievement of within 15% the prescribed blood flow rate over 3 treatments prior to study entry.

Exclusion Criteria:

* Are female and pregnant, lactating, or planning to become pregnant during the study period. Note: Female subjects of childbearing potential, defined as a woman \<55 years old who has not had a partial or full hysterectomy or oophorectomy, must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test at screening. Subjects of childbearing potential must use a medically acceptable means of contraception during their participation in the study.
* Have chronic liver disease.
* Have a known paraprotein-associated disease.
* Have known bleeding disorders (e.g., gastrointestinal bleed, colonic polyps, small bowel angiodysplasia, and active peptic ulcers).
* Have had a major bleeding episode (i.e. soft tissue bleeding, blood in stool, prolonged nose bleeds, joint damage, retinal bleeding, extensive mucosal bleeding, exsanguination, cerebral hemorrhage) ≤ 12 weeks prior to randomization.
* Have had a blood (red blood cell) transfusion ≤ 12 weeks prior to randomization.
* Have had an acute infection ≤ 4 weeks prior to randomization.
* Have active cancer, except for basal cell or squamous cell skin cancer.
* Have a known serum κ/λ FLC ratio that is less than 0.37, or greater than 3.1.b
* Have a known monoclonal gammopathy (monoclonal gammopathy of uncertain significance, smoldering \[asymptomatic\] multiple myeloma, symptomatic multiple myeloma, plasmacytomas, or plasma cell leukemia).
* Have a known polyclonal gammopathy (connective tissue disease, liver disease, chronic infection, lymphoproliferative disorder, or other hematologic condition).
* Have a positive serology test for human immunodeficiency virus or hepatitis infection.
* Have a significant psychiatric disorder or mental disability.
* Are scheduled for planned interventions requiring hospitalization \> 1 week.
* Are scheduled for living-donor transplantation within the study period + 3 months, plan to change to PD therapy within the next 9 months, plan to change to a home hemodialysis treatment, or plan to relocate to an area where no study center is located.
* Are currently participating in another interventional clinical study or has participated in another interventional clinical study in the past 3 months.
* Have a history of non-compliance with HD as assessed by an investigator.
* Have had a major cardiovascular or cerebrovascular event within 3 months of study entry.
* Have a history with consistent evidence of intradialytic hypotension.
* Have uncontrolled (systolic BP \> 180 mmHg) hypertension.
* Have had adverse reactions to dialyzer materials.

Primary outcomes:
measure: Reduction Ratio of Lambda Immunoglobulin FLC at Week 24
timeFrame: Week 24
measure: Pre-dialysis Serum Level of Albumin at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Reduction Ratio of Lambda Immunoglobulin FLC at Week 4 and Week 24
timeFrame: Week 4 and Week 24
measure: Reduction Ratio of Complement Factor D
timeFrame: Week 4 and 24
measure: Reduction Ratio of κ FLC
timeFrame: Week 4 and 24
measure: Reduction Ratio of Interleukin 6
timeFrame: Week 4 and 24
measure: Reduction Ratio of Tumor Necrosis Factor Alpha
timeFrame: Week 4 and 24
measure: Reduction Ratio of β2-microglobulin
timeFrame: Week 4 and 24
measure: Change From Baseline in Pre-dialysis β2-microglobulin at Week 24
timeFrame: Baseline, Week 24
measure: Kt/Vurea
timeFrame: Week 4, 8, 12, 16, 20, 24
measure: Change From Baseline in Pre-dialysis Serum Albumin by Visit
timeFrame: Baseline, Week 4, 8, 12, 16, 20, 24
measure: Change From Baseline in Pre-dialysis Factor VII by Visit
timeFrame: Baseline, Week 12, Week 24
measure: Change From Baseline in Pre-dialysis Protein C by Visit
timeFrame: Baseline, Week 12, Week 24
measure: Change From Baseline in Pre-dialysis Vitamin A by Visit
timeFrame: Baseline, Week 4, Week 24
measure: nPNA (nPCR)
timeFrame: Week 4, 8, 12, 16, 20, 24
measure: Change From Baseline in Pre-dialysis Factor II by Visit
timeFrame: Baseline, Week 12, Week 24
measure: Change From Baseline in Sodium (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline and Week 24
measure: Change From Baseline in Potassium (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline and Week 24
measure: Change From Baseline in Calcium (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Phosphate (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Chloride (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Bicarbonate (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Glucose (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Prothrombin Time (Sec) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Prothrombin Intl. Normalized Ratio at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Activated Partial Thromboplastin Time (Sec) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Hematocrit (L/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Hemoglobin (g/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin (pg) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Erythrocyte Mean Corpuscular HGB Concentration (g/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Erythrocyte Mean Corpuscular Volume (fL) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Platelets at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Erythrocytes at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Leukocytes at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Basophils (%) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Eosinophils (%) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Lymphocytes (%) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Monocytes (%) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Neutrophils (%) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Pre-Dialysis Blood Urea Nitrogen (mmol Urea/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Post-Dialysis Blood Urea Nitrogen (mmol Urea/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in BUN Reduction Ratio at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Creatinine (μmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Kt/Vurea by Visit
timeFrame: Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
measure: Change From Baseline in Vitamin A (μmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Cholesterol (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in HDL Cholesterol (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in LDL Cholesterol (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Triglycerides (mmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Alkaline Phosphatase (U/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Alanine Aminotransferase (U/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Aspartate Aminotransferase (U/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Direct Bilirubin (μmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Bilirubin (μmol/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Gamma Glutamyl Transferase (U/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Protein (g/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Globulin (g/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in High-sensitivity C-reactive Protein (mg/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Prothrombin Activity (%) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Albumin (g/dL) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Factor XIV Activity (%) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Tumor Necrosis Factor (pg/mL) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Factor VII Activity (%) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Lambda Light Chain, Free (mg/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Interleukin 6 (pg/mL) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Complement Factor D (mcg/mL) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Kappa Light Chain, Free (mg/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Beta-2 Microglobulin (mg/L) at End of Study (up to Week 24)
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Corona
country: United States
facility: DaVita Corona
state: California
city: Riverside
country: United States
facility: DaVita Riverside
state: California
city: Bloomfield
country: United States
facility: DaVita Inc, Greater Hartford Nephrology
state: Connecticut
city: Middlebury
country: United States
facility: DaVita Inc., Waterbury Dialysis
state: Connecticut
city: Albany
country: United States
facility: Dialysis Center, Inc. Albany
state: Georgia
city: Boston
country: United States
facility: Dialysis Center, Inc. Boston
state: Massachusetts
city: Belton
country: United States
facility: Dialysis Center, Inc. Kidney Associates of Kansas City
state: Missouri
city: Lincoln
country: United States
facility: Dialysis Center of Lincoln
state: Nebraska
city: Las Vegas
country: United States
facility: DaVita Five Star Dialysis Center
state: Nevada
city: Las Vegas
country: United States
facility: DaVita Inc., South Las Vegas Dialysis
state: Nevada
city: North Brunswick
country: United States
facility: Dialysis Center, Inc. North Brunswick
state: New Jersey
city: Bronx
country: United States
facility: DaVita Inc., Bronx Dialysis Center
state: New York
city: Philadelphia
country: United States
facility: Dialysis Center, Inc. Philidelphia
state: Pennsylvania
city: Knoxville
country: United States
facility: Dialysis Center, Inc. Holston River Clinic
state: Tennessee
city: El Paso
country: United States
facility: DaVita Inc., Transmountain Dialysis
state: Texas
city: Houston
country: United States
facility: DaVita Inc., Medical Center Dialysis
state: Texas
city: Lewisville
country: United States
facility: DaVita Renal Center of Lewisville
state: Texas
city: San Antonio
country: United States
facility: DaVita Inc., Northwest Medical Center Dialysis
state: Texas
city: San Antonio
country: United States
facility: DaVita Floyd Curl Dialysis
state: Texas
city: Chesapeake
country: United States
facility: DaVita Inc., Norfolk Dialysis
state: Virginia
Study officials:
References:
citation: Weiner DE, Falzon L, Skoufos L, Bernardo A, Beck W, Xiao M, Tran H. Efficacy and Safety of Expanded Hemodialysis with the Theranova 400 Dialyzer: A Randomized Controlled Trial. Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1310-1319. doi: 10.2215/CJN.01210120. Epub 2020 Aug 25.