Cardiovascular Risk Comparison Between Expanded Hemodialysis Using Theranova and On-line Hemodiafiltration

Study Overview
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Brief Summary
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Theranova is a novel medium cut-off (MCO) dialyzer. Previous studies identified that theranova dialyzer had superior performance on middle molecule removal to conventional hemodialysis (HD) and hemodiafiltration (HDF). The present study addresses to compare clinical outcomes including cardiovascular endpoint between HD with theranova dialyzer and HDF.

Detailed Description
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While conventional hemodialysis (HD) modality effectively removes small-sized molecules, performance with middle-sized and protein-bound molecules is not well established. With increasing perception on importance of middle molecule removal, on-line hemodiafiltration (HDF) is getting more attention from healthcare professionals. However, HDF has not been widely used in Korea due to its technical burden and limited public funding issue. Novel medium cut-off (MCO) dialyzer, Theranova, is available in Korea, which showed superior performance on middle molecule removal to conventional HD and HDF from the previous study. This new dialyzer can be a good alternative option replacing conventional HD or even HDF with its benefits. However, current data available on the MCP dialyzer has certain limitations such as small sample size, no Asian subject included, limited types of biomarkers, and no clinical outcomes (particularly cardiovascular diseases) included. With this respect, performance comparison of MCO dialyzer with HDF in terms of clinical outcomes, including cardiovascular endpoint would fill the exiting data gap, which is absolutely important to make a clinical decision on dialysis modality.

Official Title
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Cardiovascular Risk Comparison Between Expanded Hemodialysis Using Theranova and On-line Hemodiafiltration - Exploratory, Multicenter, Randomized Clinical Trial

Conditions
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Kidney Failure, Chronic, Renal Dialysis

Intervention / Treatment
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* Device: Theranova
* Device: Online hemodiafiltration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old and older Hemodialysis more than 3 months because of end-stage renal disease Consent to the study protocol Exclusion Criteria: Already receiving online hemodiafiltration before study enrollment Dialysis schedule other than three times per week (e.g., once per week) Receiving concurrent peritoneal dialysis Having a plan to receive kidney transplantation within 1 year Having multiple myeloma or monoclonal gammopathy Having advanced or active malignancy Having a plan to be pregnant or being pregnant / breast-feeding or not having a plan to use contraception Participating in other clinical trials

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Exploratory, Multicenter, Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>Extended HD with MCO dialyzer | Device: Theranova<br>* Extended HD with theranova<br>|
| Active Comparator: Control group<br>Online hemodiafiltration | Device: Online hemodiafiltration<br>* Online hemodiafiltration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiovascular surrogate marker | Brachial-ankle pulse wave velocity (m/s) | 0, 6, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cardiac surrogate marker #1 | CT coronary calcium scoring (score) | 0, 6, 12 months | 
| Change in cardiac surrogate marker #2 | Echocardiography: ejection fraction (%); E/e' ratio (cm/s per cm/s); LVMI (g/m2). | 0, 6, 12 months | 
| Change in cardiovascular biomarkers #1 | Plasma levels of BNP (pg/ml) | 0, 6, 12 months | 
| Change in cardiovascular biomarkers #2 | Plasma levels of NT-proBNP (pg/ml) | 0, 6, 12 months | 
| Change in cardiovascular biomarkers #3 | Plasma levels of hsCRP (mg/dl) | 0, 6, 12 months | 
| Change in cardiovascular biomarkers #4 | Plasma levels of troponin-I (ng/ml) | 0, 6, 12 months | 
| Change in cardiovascular biomarkers #5 | Plasma levels of troponin-T (ng/ml) | 0, 6, 12 months | 
| Change in cardiovascular biomarkers #6 | Plasma levels of IL-6 (pg/ml) | 0, 6, 12 months | 
| Patient-reported outcomes #1 | Dialysis symptom index (score) | 0, 6, 12 months | 
| Patient-reported outcomes #2 | Degree of fatigue after dialysis (scale from 0 to 10) | 0, 6, 12 months | 
| Patient-reported outcomes #3 | Post-dialysis recovery time (within minutes, when arriving home, at bed time, next morning, by next dialysis) | 0, 6, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodiafiltration, End-stage renal disease, Medium cut-off dialyzer, Cardiovascular, Pulse wave velocity