Clinical trial NCT04106310: Theranova vs High-flux HD Comparison
Official title: The Comparison of Expanded Dialysis With Theranova Dialyzer With Conventional High-flux Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Renal Failure on Dialysis
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Baxter Healthcare Corporation
First posted: 2019-09-27
Enrollment: 60
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: 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)

Eligibility criteria: 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

Primary outcomes:
measure: lean tissue index
timeFrame: 12 months
measure: Body Mass Index
timeFrame: 12 months
Secondary outcomes:
measure: asymmetrical dimethylarginine
timeFrame: 12 months
measure: fibroblast growth factor 23
timeFrame: 12 months
measure: Klotho
timeFrame: 12 months
measure: Kt/V urea
timeFrame: 12 months
measure: beta-2 microglobulin
timeFrame: 12 months
measure: Pentraxin-3
timeFrame: 12 months
measure: soluble endothelial protein C receptor
timeFrame: 12 months
measure: soluble thrombomodulin
timeFrame: 12 months
measure: hemoglobulin
timeFrame: 12 months
measure: high-sensitive C reactive protein
timeFrame: 12 months
measure: interleukin 6
timeFrame: 12 months
measure: tumor necrosis factor alpha
timeFrame: 12 months
measure: albumin
timeFrame: 12 months
measure: Leptin
timeFrame: 12 months
measure: adiponectin
timeFrame: 12 months
measure: phosphate
timeFrame: 12 months
measure: low-density lipoprotein
timeFrame: 12 months
measure: high-density lipoprotein
timeFrame: 12 months
measure: triglyceride
timeFrame: 12 months
measure: Malnutrition-Inflammation Score
timeFrame: 12 months
measure: Subjective Global Assesment questionnaire
timeFrame: 12 months
measure: fat tissue index
timeFrame: 12 months
measure: admission rate due to cardiovascular events
timeFrame: 12 months
measure: admission rate due to infection
timeFrame: 12 months
measure: mortality rate
timeFrame: 12 months
measure: 5-D itch scale
timeFrame: 12 months
measure: Numeric rating scale for itchiness
timeFrame: 12 months
measure: The Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score
timeFrame: 12 months
measure: Visual analogue scale for appetite
timeFrame: 12 months
measure: Postdialysis recovery time
timeFrame: 12 months
measure: Self-reported sleep quality
timeFrame: 12 months
measure: Hong Kong Montreal Cognitive Assessment
timeFrame: 12 months
measure: KDQOLSFTMv1.3 questionnaire
timeFrame: 12 months
measure: DNA methylation analysis of TRPV1 gene
timeFrame: 12 months
measure: DNA methylation analysis of LY96 gene
timeFrame: 12 months
measure: DNA methylation analysis of IFNGR1 gene
timeFrame: 12 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Division of Nephrology, Department of Medicine, Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Tung Wah Hospital
Study officials:
affiliation: The University of Hong Kong
name: Maggie Ming Yee Mok, MBBS, MRCP
role: PRINCIPAL_INVESTIGATOR
References: