Theranova vs High-flux HD Comparison

Not Applicable

Completed

• Conditions: End Stage Renal Failure on Dialysis
• Interventions: Device: Theranova dialyzer; Device: High-flux dialyzer

• Registration Number: NCT04106310
• Lead Sponsor: The University of Hong Kong

Brief Summary

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.

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 Timeline

• Study First Submitted: 2019-09-10
• Study First Submitted QC: 2019-09-24
• Study First Posted: 2019-09-27
• Study Start: 2019-11-01
• Primary Completion: 2021-06-30
• Study Completion: 2021-06-30
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-28
• Last Update Posted: 2021-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Theranova	Theranova dialyzer	Patients will be receiving hemodialysis using Theranova dialyzer. The other hemodialysis parameters are kept the same.
High-flux	High-flux dialyzer	Patients will be receiving hemodialysis using a high-flux dialyzer. The other hemodialysis parameters are kept the same

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Tung Wah Hospital; 🇭🇰 Hong Kong, Hong Kong

Division of Nephrology, Department of Medicine, Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong