Theranova vs High-flux HD Comparison

The Comparison of Expanded Dialysis With Theranova Dialyzer With Conventional High-flux Hemodialysis

This research proposal of an investigator-initiated clinical study aims to examine the impact of uremic toxin removal afforded by middle cut-off (MCO) dialysis on clinical parameters and surrogate biomarkers pertinent to nutritional, systemic and vascular complications in dialysis patients. The primary research goal is to evaluate the outcomes indicative of nutritional status (as measured by body mass index, body composition monitoring, albumin, clinical assessments such as subjective global assessment, etc.) and parameters relevant to pathophysiological processes in uremia focusing on inflammation and cardiovascular risks. The secondary research aims are to examine dialysis efficacy between MCO dialysis and conventional hemodialysis (CHD). Specifically, dialysis efficacy will be determined by within and between subject differences in baseline versus short term (6 months) and long term (12 months) effects of MCO dialysis and CHD in:

1. Removal of small molecules (e.g. urea), middle molecules (Beta-2 microglobulin, Phosphate and Creatinine) and protein bound solutes
2. Markers of inflammation, ossification and fibrosis
3. Uremia associated epigenetic modification The investigators hypothesize superiority of nutritional parameters in patients undergoing MCO dialysis compared with patients on CHD. The investigators plan to randomize 60 patients to either MCO dialysis or CHD at two hemodialysis units in Hong Kong.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Failure on Dialysis
• Intervention / Treatment: Device: Theranova dialyzer; Device: High-flux dialyzer

Detailed Description

Accumulation of uremic toxins is associated morbidity and mortality in patients with end-stage renal disease, but the pathogenic mechanisms how they lead to various clinical complications remain elusive. Conventional hemodialysis is effective in removing small molecular solutes (in the range of 50-15,000 Da), but the removal of protein-bound and middle to larger molecular toxins (up to 50,000 Da) remains unsatisfactory even with augmented hemodialysis frequency or duration. The notion that dialysis adequacy is no longer a simple quantitative measure of small molecular removal has led to the clinical application of intensive hemodialysis and the search for novel strategies to reduce uremic toxin burden.

Recently, a new class of membrane with molecular weight cut off (MWCO) close to the molecular weight of albumin was introduced. The focus of this new therapy, known as expanded dialysis using the medium cut off (MCO) dialysis membrane, is to provide the potential for more efficient removal of middle molecules and protein bound uremic toxins without excessive loss of albumin. To date, MCO dialysis has been associated with a reduction in transcription of pro-inflammatory cytokines (i.e. interleukin 6 and tumor necrosis factor-α) and middle molecules especially free lambda light chains.

Protein-energy wasting and cardiovascular diseases are prevalent in chronic kidney disease and is related to inflammation and increased mortality. Despite growing data on the clearance of individual uremic toxins and biochemical parameters, the impact of MCO dialysis on clinical outcomes and mechanistic parameters related to nutrition and inflammation remains to be investigated.

The objective of the study is to compare MCO dialysis with conventional high-flux HD, on nutritional parameters, inflammation and cardiovascular biomarkers and related clinical outcomes.

Since twice-weekly HD is commonly practiced in Hong Kong, this study provides a distinct opportunity to investigate whether MCO dialysis might be particularly advantageous in patients receiving a relatively lower dialysis dose through the removal of a broader spectrum of uremic toxins.

The investigators hypothesize that MCO dialysis with Theranova Dialyzer (HDx) improves parameters related to nutrition and inflammation compared with high-flux HD.

This will be a prospective single-blinded, randomized, controlled trial with stable HD patients randomized at 1:1 ratio to either one of the following - A. to continue with HD using the same high-flux dialyzer as in the previous 6 weeks (high-flux HD arm) B. change to HDx using Theranova Dialyzer (MCO dialysis arm)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Tung Wah Hospital
  • Hong Kong, Hong Kong
    • Division of Nephrology, Department of Medicine, Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients age greater than 18 years old
• end-stage renal failure on two- or three-times per week high-flux HD for more than 90 days
• mean spKt/Vurea >1.2 per session (for 3 dialysis sessions per week) or spKt/Vurea >1.8 per session (for 2 dialysis sessions per week)

Exclusion Criteria:

• active malignancy
• unable to give informed consent or complete questionnaires
• unstable clinical condition defined as significant clinical event requiring hospitalization in the past 90 days
• unreliable vascular access
• unable to achieve HD blood flow >150ml/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Theranova; Patients will be receiving hemodialysis using Theranova dialyzer. The other hemodialysis parameters are kept the same.	Device: Theranova dialyzer; a middle cut-off dialyzer
Active Comparator: High-flux; Patients will be receiving hemodialysis using a high-flux dialyzer. The other hemodialysis parameters are kept the same	Device: High-flux dialyzer; a dialyzer meeting the definition of high-flux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lean tissue index	measured by Body Composition Monitor	12 months
Body Mass Index	measured by weight (in kilograms) divided by the square of heights (in meters)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
asymmetrical dimethylarginine	endogenous inhibitor of nitric oxide synthase, one of the cardiovascular biomarkers	12 months
fibroblast growth factor 23	biomarker for bone turnover	12 months
Klotho	biomarker for atherosclerosis and bone turnover	12 months
Kt/V urea	measurement of clearance of urea by hemodialysis therapy, a marker for adequacy of dialysis	12 months
beta-2 microglobulin	middle size uremic toxin	12 months
Pentraxin-3	middle to large molecular size uremic toxin	12 months
soluble endothelial protein C receptor	a marker for endothelial dysfunction	12 months
soluble thrombomodulin	a marker for endothelial dysfunction	12 months
hemoglobulin	indication of anemia	12 months
high-sensitive C reactive protein	marker for inflammation	12 months
interleukin 6	marker for inflammation	12 months
tumor necrosis factor alpha	marker for inflammation	12 months
albumin	marker for nutritional status	12 months
Leptin	marker for nutritional status and appetite	12 months
adiponectin	nutritional marker	12 months
phosphate	small size uremic waste produce	12 months
low-density lipoprotein	reflects lipid control	12 months
high-density lipoprotein	reflects lipid control	12 months
triglyceride	reflects lipid control	12 months
Malnutrition-Inflammation Score	a measurement scale reflecting nutritional status	12 months
Subjective Global Assesment questionnaire	a measurement scale reflecting nutritional status	12 months
fat tissue index	nutritional marker measured by Body Composition Monitor	12 months
admission rate due to cardiovascular events	number of admisisons due to cardiovascular events during the follow-up period	12 months
admission rate due to infection	number of admissions due to infection during the follow-up period	12 months
mortality rate	number of deaths during the follow-up period	12 months
5-D itch scale	Symptomatology scale to measure itchiness	12 months
Numeric rating scale for itchiness	Symptomatology scale to measure itchiness	12 months
The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score	measurement scale for appetite	12 months
Visual analogue scale for appetite	measurement scale for appetite	12 months
Postdialysis recovery time	number of time required to feel well after receiving a hemodialysis session	12 months
Self-reported sleep quality	scale to rate the quality of sleep	12 months
Hong Kong Montreal Cognitive Assessment	measurement of cognitive function	12 months
KDQOLSFTMv1.3 questionnaire	quality of life assessment	12 months
DNA methylation analysis of TRPV1 gene	epigenetics modification	12 months
DNA methylation analysis of LY96 gene	epigenetics modificaiton	12 months
DNA methylation analysis of IFNGR1 gene	epigenetics modifications	12 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: Baxter Healthcare Corporation
• Investigators: Principal Investigator: Maggie Ming Yee Mok, MBBS, MRCP, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: September 10, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 27, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: Version 1 13th Aug 2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No