Theranova vs High-flux HD Comparison

End Stage Renal Failure on Dialysis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04106310
• Other study ID #: Version 1 13th Aug 2019
• Status: Completed
• Phase: N/A
• Start date: November 1, 2019
• Est. completion date: June 30, 2021

Study information

• Verified date: September 2021
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End Stage Renal Failure on Dialysis
• Kidney Failure, Chronic

Intervention

Device:
• High-flux dialyzer
a dialyzer meeting the definition of high-flux
• Theranova dialyzer
a middle cut-off dialyzer

Locations

Country	Name	City	State
Hong Kong	Division of Nephrology, Department of Medicine, Queen Mary Hospital	Hong Kong
Hong Kong	Tung Wah Hospital	Hong Kong

Sponsors (2)

Lead Sponsor	Collaborator
The University of Hong Kong	Baxter Healthcare Corporation

Country where clinical trial is conducted

Hong Kong, 

Outcome

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