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

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Inflammation; End Stage Renal Disease
• Intervention / Treatment: Device: Medium Cut-Off Haemodialysis; Device: On-Line Haemodiafiltration

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 Type: Interventional
• Enrollment (Actual): 63
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Lancashire
    • Manchester, Lancashire, United Kingdom, M13 9WL
      • Manchester NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in endothelial function (composite of endothelial microvesicle levels, pro-inflammatory & pro-coagulant markers)	Change in vascular endothelial marker score (derived from multiple biomarkers)	6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Manchester University NHS Foundation Trust
• Collaborators: Baxter Healthcare Corporation; Manchester Metropolitan University
• Investigators: Principal Investigator: Sandip Mitra, MBBS, Manchester University NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2018
• Primary Completion (Actual): May 9, 2019
• Study Completion (Actual): May 9, 2019

Study Registration Dates

• First Submitted: April 12, 2018
• First Submitted That Met QC Criteria: April 26, 2018
• First Posted (Actual): April 27, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Pulse Wave Velocity; Hemodialysis; Haemodialysis; Haemodiafiltration; Hemodiafiltration; Dialysis membrane; Endothelial Microvesicles
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Cardiovascular Diseases; Inflammation; Kidney Failure, Chronic
• Other Study ID Numbers: R04863

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: This is yet to be determined

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No