MoDal: Comparison of MCO HD on Markers of Vascular Health Compared With On-Line Haemodiafiltration

Sponsor

Manchester University NHS Foundation Trust (Other)

Overall Status

Completed

CT.gov ID

NCT03510520

Collaborator

Manchester Metropolitan University (Other), Baxter Healthcare Corporation (Industry)

Enrollment

Location

Arms

7.8

Actual Duration (Months)

8.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease Cardiovascular Diseases Inflammation	Device: Medium Cut-Off Haemodialysis Device: On-Line Haemodiafiltration	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a single-centre, pilot, open-label, interventional, randomised controlled study.This is a single-centre, pilot, open-label, interventional, randomised controlled study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomised Study Investigating the Effect of Medium Cut-Off Haemodialysis On Markers of Vascular Health Compared With On-Line HDF

Actual Study Start Date :

Sep 14, 2018

Actual Primary Completion Date :

May 9, 2019

Actual Study Completion Date :

May 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Medium Cut-Off Haemodialysis (Theranova) Participants will receive medium cut-off haemodialysis treatment for 6 months in total (3 times per week treatment).	Device: Medium Cut-Off Haemodialysis Treatment with medium cut-off haemodialysis using the Theranova dialysis membrane 3 times per week for 6 months
Active Comparator: On-Line Haemodiafiltration Participant will remain on their usual on-line haemodiafiltration (HDF) treatment for the 6 month study duration (3 times per week treatment).	Device: On-Line Haemodiafiltration Treatment with on-line haemodiafiltration (HDF) 3 times per week for 6 months (Conventional treatment)

Arm

Intervention/Treatment

Experimental: Medium Cut-Off Haemodialysis (Theranova)

Participants will receive medium cut-off haemodialysis treatment for 6 months in total (3 times per week treatment).

Device: Medium Cut-Off Haemodialysis

Treatment with medium cut-off haemodialysis using the Theranova dialysis membrane 3 times per week for 6 months

Active Comparator: On-Line Haemodiafiltration

Participant will remain on their usual on-line haemodiafiltration (HDF) treatment for the 6 month study duration (3 times per week treatment).

Device: On-Line Haemodiafiltration

Treatment with on-line haemodiafiltration (HDF) 3 times per week for 6 months (Conventional treatment)

Outcome Measures

Primary Outcome Measures

Change in endothelial function (composite of endothelial microvesicle levels, pro-inflammatory & pro-coagulant markers) [6 months]
Change in vascular endothelial marker score (derived from multiple biomarkers)

Secondary Outcome Measures

Change in pulse wave velocity [6 months]
Change in pulse wave velocity as measured by non-invasive pulse wave analysis device
Change in pre-dialysis serum albumin [3 & 6 months]
Change in pre-dialysis serum albumin
Change in pre-dialysis CRP [3 & 6 months]
Change in pre-dialysis CRP
Change in components of pre-dialysis "middle molecule" panel [3 & 6 months]
Change in components of pre-dialysis "middle molecule" panel (this includes beta 2 microglobulin, serum free light chains, leptin, beta trace protein and prolactin)
Change in components of cytokine panel [3 & 6 months]
Change in components of cytokine panel (including IL-6, TNFa, ICAM & VEGF)
Change in numbers blood pressure medications [6 months]
Change in numbers blood pressure medications
Change in number of phosphate binder medications [6 months]
Change in number of phosphate binder medications
Change in Advanced Glycation End Products (AGE) [6 months]
Change in Advanced Glycation End Products (AGE)
Change in inter-dialytic urine volume [6 months]
Change in inter-dialytic urine volume
Change in IPOS-Renal (Integrated Palliative Care Outcome Score) [3 & 6 months]
Change in IPOS-Renal (Integrated Palliative Care Outcome Score)
Change in self-sported dialysis recovery time [3 & 6 months]
Change in self-sported dialysis recovery time
Change in Chalder fatigue scale [3 & 6 months]
Change in Chalder fatigue scale (score range 0 to 33, high score indicating high levels of fatigue)
Hospitalisation episodes [6 months]
Number of hospitalisation episodes during 6 months study period
All-cause mortality [6 months]
All-cause mortality
Cardiovascular mortality [6 months]
Cardiovascular mortality
Change in augmentation pressure (AP) [6 months]
Change in segmentation pressure as measured by non-invasive pulse wave analysis device
Change in heart-rate adjusted augmentation index (AI) [6 months]
Change in heart-rate adjusted augmentation index (AI) as measured by non-invasive pulse wave analysis device

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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