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CompletedNCT03288922Updated Jan 25, 2018

Protein-bound Toxin Removal Between Limited Blood Flow Super High-flux Online HDF and High-Efficiency Online HDF

An interventional study of Limited BF OL-HDF with SHF and High-efficiency OL-HDF in End-stage Renal Disease and Hemodialysis, sponsored by Chulalongkorn University. Completed at 1 site in Thailand. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-01-25.

Sponsored by Chulalongkorn University · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
10
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

High-efficiency post-dilution online hemodiafiltration (OL-HDF) using high-flux dialyzer and requiring high blood flow rate (BF ≥400 mL/min) has been reported to enhance protein-bound toxin and middle molecular toxin removal and improve patient survival. Unfortunately, the majority of patients could not reach that high BF because of vascular access issue. This randomized crossover study was conducted to compare these uremic toxin removals between the new modality (limited BF OL-HDF with super high-flux dialyzer) and the control (high-efficiency OL-HDF). The OL-HDF patients were randomized to undergo either new modality or control for 2 weeks before crossover to the other modality for another 2 weeks.

Read the detailed description

Elevated protein-bound toxins including p-cresol (pCS) and indoxyl sulfate (IDS) as well as middle-molecular toxins such as beta2-microglobulin (B2M) which could not be removed by hemodialysis (HD) are obviously correlated with high mortality. High-efficiency post-dilution online hemodiafiltration (OL-HDF) using high-flux dialyzer and requiring high blood flow rate (BF ≥400 mL/min) has been reported to enhance pCS, IDS, and B2M removal and improve patient survival. Unfortunately, the majority of patients could not reach that high BF because of vascular access issue. We innovated the OL-HDF modality for this limited BF situation by integrating the novel super high-flux membrane dialyzer (SHF; PES-17Dα, Nipro Corporation, Japan) into pre-dilution OL-HDF. This randomized crossover study was conducted to compare the uremic toxin removals between the new modality (limited BF OL-HDF with SHF) and the control (high-efficiency OL-HDF). The OL-HDF patients were randomized to undergo either new modality or control for 2 weeks before crossover to the other modality for another 2 weeks. Removals of pCS and IDS as well as small and middle molecule toxins were compared. The pCS and IDS were measured by high performance liquid chromatography. The dialysate albumin loss and patient safety were also monitored.

02

Conditions studied

  • End-stage Renal Disease
  • Hemodialysis

Keywords

  • Online Hemodiafiltration
  • Super high-flux dialyzer
  • Protein-bound uremic toxin
  • P-cresol
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • End-stage renal disease patients treated with thrice-a-week OL-HDF for at least 6 months
  • Residual urine \< 100 mL/day

Exclusion criteria

Exclusion Criteria:

  • Active cardiovascular disease
  • Active malignancy
  • Pregnancy
  • Breast-feeding
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
10 participants (actual)

Study arms

  • Experimental
    Limited BF OL-HDF with SHF

    Limited blood flow pre-dilution online hemodiafiltration using super high-flux dialyzer which had larger pore size than standard high-flux dialyzer was assigned as the new intervention to compare the efficacy of protein-bound toxin removals with the control period.

    Procedure: Limited BF OL-HDF with SHF

  • Active comparator
    High-efficiency OL-HDF

    High-efficiency post-dilution online hemodiafiltration using standard high-flux dialyzer was assigned as the control period.

    Procedure: High-efficiency OL-HDF

Interventions

  • ProcedureLimited BF OL-HDF with SHF

    The new modality "Limited BF OL-HDF with SHF" were performed using Fresenius 5008 hemodiafiltration machine. The prescribed blood flow rate was 300 ml/min and the total dialysis fluid flow rate was 800 ml/min which included pre-filter substitution rate of 150 ml/min. The super high-flux dialyzer was PES-17Dα from Nipro Corporation, Japan which contains 1.7 m2 hollow fiber polyethersulfone membrane (ultrafiltration coefficient 80 ml/h/mmHg; urea clearance 267 ml/min, Qb 300 ml/min and Qd 500ml/min). The patients were received this treatment thrice-a-week for 2 week before entering the wash-out period and crossover to another arm.

  • ProcedureHigh-efficiency OL-HDF

    The controlled modality "High-efficiency OL-HDF" were performed using Fresenius 5008 hemodiafiltration machine. The prescribed blood flow rate was 400 ml/min and the total dialysis fluid flow rate was 800 ml/min which included post-filter substitution rate of 100 ml/min. The standard high-flux dialyzer that was used was HF80s from Fresenius Medical Care, Germany contains 1.8 m2 hollow fiber polysulfone membrane (ultrafiltration coefficient 55 ml/h/mmHg; urea clearance 248 ml/min, Qb 300ml/min and Qd 500 ml/min). The patients were received this treatment thrice-a-week for 2 week before entering the wash-out period and crossover to another arm.

05

What researchers measure

Primary outcomes

  1. pCS percentage of reduction ratio

    Blood samples were taken from patients before and at the end of 4-hour in the first dialysis session of each modality. pCS levels were measured by high-performance liquid chromatography (HPLC). The percentage of reduction ratio were calculated from the before and ending samples.

    Time frame: At time 0-hour and 4-hour of the study online hemodiafiltration session

Secondary outcomes

  1. IDS percentage of reduction ratio

    Blood samples were taken from patients before and at the end of 4-hour in the first session of each modality. IDS levels were measured by high-performance liquid chromatography (HPLC). The percentage of reduction ratio were calculated from the before and ending samples.

    Time frame: At time 0-hour and 4-hour of the study online hemodiafiltration session

  2. Beta2-microglobulin percentage of reduction ratio

    Blood samples were taken from patients before and at the end of 4-hour in the first dialysis session of each modality. The percentage of reduction ratio were calculated from the before and ending samples.

    Time frame: At time 0-hour and 4-hour of the study online hemodiafiltration session

  3. Albumin loss in spent dialysate

    Continuous sampling of spent effluent dialysate and ultrafiltrate were carried out with a collection pump inserted into the effluent outlet line via a special connector for total albumin loss determination.

    Time frame: During 4 hours of online hemodiafiltration session

06

Study locations

1 site
  • Chulalongkorn Hospital
    Bangkok, 10330, Thailand
07

Registry details

Key details

Study ID
NCT03288922
Lead sponsor
Chulalongkorn University
Responsible party
Khajohn Tiranathanagul (Associate Professor, Chulalongkorn University) — Principal investigator
First posted
Sep 20, 2017
Start date
Oct 2016
Primary completion
Oct 2017
Completion
Jan 2018
Last update
Jan 25, 2018

Study contacts

Khajohn Tiranathanagul, MD
principal investigator · Chulalongkorn University
Wanjak Pongsittisak
principal investigator · Chulalongkorn University

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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