Clinical trial NCT03510520: Comparison of MCO HD on Markers of Vascular Health Compared With On-Line Haemodiafiltration
Official title: A Randomised Study Investigating the Effect of Medium Cut-Off Haemodialysis On Markers of Vascular Health Compared With On-Line HDF
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Renal Disease
Cardiovascular Diseases
Inflammation
Keywords: Hemodialysis
Haemodialysis
Hemodiafiltration
Haemodiafiltration
Dialysis membrane
Endothelial Microvesicles
Pulse Wave Velocity
Lead sponsor: Manchester University NHS Foundation Trust
Sponsor class: OTHER_GOV
Collaborators: name: Manchester Metropolitan University
name: Baxter Healthcare Corporation
First posted: 2018-04-27
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a single-centre, pilot, open-label, interventional, randomised controlled study.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate haemodialysis treatment using a medium cut-off dialysis membrane (Theranova) compared with on-line haemodiafiltration treatment with respect to markers of endothelial health (plasma endothelial microvesicle levels, pro-inflammatory and pro-coagulant markers).

This study will also compare the 2 treatment modalities with respect to several other outcome measures including patient-reported outcome measures, haemodynamic parameters and advanced glycation end-products.

Detailed description: To date, methods of improving outcomes for haemodialysis patients have focused on improving small molecule clearance (urea); however, the benefits do not appear to be linear and increasing Kt/V above 1.3 shows no benefit. Current dialysis therapies are unable to provide effective clearance of larger "middle molecules" (between 20kDa and 60kDa) and retention of these molecules may be linked to poor outcomes in haemodialysis patients.

Medium cut-off (MCO) dialysis membranes have been recently developed to address this area of unmet need and provide an enhanced clearance of some larger middle molecules when compared with high flux haemodialysis (HFHD) and even high volume haemodiafiltration (HDF). The clinical benefit of this therapy is yet to be defined.

The aim of this study is to investigate the effect of HDx therapy (expanded haemodialysis therapy through the use of a MCO haemodialysis membrane- Theranova) on vascular endothelial and inflammatory biomarkers compared with high volume HDF therapy. Through the use of endothelial microvesicles (EMV) as a marker of vascular endothelial health, which strongly correlate with cardiovascular outcomes in end-stage real disease (ESRD) patients, this pilot study will take the first steps into exploring whether HDx treatment provides clinical benefits in addition to its simplicity of implementation. Additionally, other important parameters, such as dialysis recovery time, patient-reported outcome measures and volume management will also be explored and compared with high volume HDF.

Eligibility criteria: Inclusion Criteria:

* Established on in-centre haemodiafiltration (HDF) for greater than 12 weeks with a minimum of 3 treatment sessions per week
* Ability to consent

Exclusion Criteria:

* Planned live donor renal transplant within 6 months (with confirmed date)
* Planned switch in renal replacement modality (ie. to peritoneal dialysis or home haemodialysis)
* Clinician predicted prognosis \< 6 months

Primary outcomes:
measure: Change in endothelial function (composite of endothelial microvesicle levels, pro-inflammatory & pro-coagulant markers)
timeFrame: 6 months
Secondary outcomes:
measure: Change in pulse wave velocity
timeFrame: 6 months
measure: Change in pre-dialysis serum albumin
timeFrame: 3 & 6 months
measure: Change in pre-dialysis CRP
timeFrame: 3 & 6 months
measure: Change in components of pre-dialysis "middle molecule" panel
timeFrame: 3 & 6 months
measure: Change in components of cytokine panel
timeFrame: 3 & 6 months
measure: Change in numbers blood pressure medications
timeFrame: 6 months
measure: Change in number of phosphate binder medications
timeFrame: 6 months
measure: Change in Advanced Glycation End Products (AGE)
timeFrame: 6 months
measure: Change in inter-dialytic urine volume
timeFrame: 6 months
measure: Change in IPOS-Renal (Integrated Palliative Care Outcome Score)
timeFrame: 3 & 6 months
measure: Change in self-sported dialysis recovery time
timeFrame: 3 & 6 months
measure: Change in Chalder fatigue scale
timeFrame: 3 & 6 months
measure: Hospitalisation episodes
timeFrame: 6 months
measure: All-cause mortality
timeFrame: 6 months
measure: Cardiovascular mortality
timeFrame: 6 months
measure: Change in augmentation pressure (AP)
timeFrame: 6 months
measure: Change in heart-rate adjusted augmentation index (AI)
timeFrame: 6 months
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Manchester NHS Foundation Trust
state: Lancashire
Study officials:
affiliation: Manchester University NHS Foundation Trust
name: Sandip Mitra, MBBS
role: PRINCIPAL_INVESTIGATOR
References: