Online Hemodiafiltration vs Conventional Hemodialysis in Acute Kidney Injury (HDFAKI)

Evaluation of the Impact of Online Hemodiafiltration vs Conventional Hemodialysis in Acute Kidney Injury on Inflammatory and Clinical Outcomes

Only limited data exist on the benefit of online hemodiafiltration in patient with Acute kidney injury. The objective of this pilot RCT is to assess the feasibility of a large multicentre RCT to determine whether, in patients with AKI requiring acute renal replacement therapy, does exposure to Online Hemodiafiltration reduce the inflammatory status and improve renal recovery compared to conventional intermittent hemodialysis at the ICU.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Device: Conventional Hemodialysis; Device: Online Pre-dilution Hemodiafiltration; Device: Online Post-dilution Hemodiafiltration

Detailed Description

Despite sparse data on the advantages of hemodiafiltration over conventional hemodialysis for intermittent dialysis, there is limited data comparing these modalities in AKI from various aetiologies in critically ill patients. As RCTs involving renal replacement therapy at the ICU are exceptionally challenging to complete, thus a rigorous RCT based on appropriate sample size and relevant clinical outcomes is crucial. The objective of this pilot RCT is to assess the feasibility of a larger multicentre RCT to determine whether, in patients with AKI requiring acute renal replacement therapy, does exposure to Post-dilution Hemodiafiltration or Pre-dilution Hemodiafiltration reduce the inflammatory status and improve renal recovery compared to conventional intermittent hemodialysis at the ICU. As post-dilution HDF has never been adequately evaluated in an ICU context, comparison between pre-dilution and post-dilution HDF is also required to confirm feasibility.

This proof-of-concept pilot trial will focus on three feasibility endpoints. It will be considered successful if the following criteria are achieved :

• Protocol adherence: If ≥85% of overall dialysis sessions are administered per-protocol according to the allocated modality
• Adherence to follow-up: If it was possible to obtain end-of-study outcomes in ≥90% of participants, and
• Participant accrual: If the average monthly enrolment is 4 or more participants per months.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X 0C1
      • Centre de recherche du CHUM
• Ireland
  • Dublin, Ireland
    • Clinical Research Centre University College Dublin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Hospitalised in the ICU
• Acute kidney injury stage 3 (KDIGO-AKI Criteria)
• Requiring RRT for AKI, as judged by the attending clinician (initiation) or conversion from CRRT to intermittent dialysis
• Adult of 18 years or more

Exclusion Criteria:

• Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study.
• Subjects who are participating in another study involving dialysis interventions
• Subjects or relatives/next-of-kin unable to provide written informed consent
• Creatinine clearance (CrCl) < 30 mL/min measured by 24-hour urine collection or eGFR or on chronic dialysis at baseline
• Subjects on active immunosuppressive therapy (>10mg of prednisone, biologic therapies, calcineurin inhibitors, mTOR inhibitors or antimetabolites)
• Subjects with active contraindication to anticoagulation during dialysis session
• Subjects whose RRT is not part of their life goal

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional Hemodialysis; Participants will receive intermittent HD for a minimum of 4hours per session, 3 to 4 times/week, using the 5008 High-Volume HDF Machine from Fresenius Medical Care with High Flux FX1000 Dialyzer (Mode HD).	Device: Conventional Hemodialysis; Using the following parameters: maximum Blood flow rate allowed by vascular access, dialysate rate of 500 mL/min, no convection. The dialysate composition, net ultrafiltration rate and use of anticoagulation will be prescribed according to participant's characteristics.
Experimental: Pre-dilution Hemodiafiltration; Participants will receive intermittent pre-dilution HDF for a minimum of 4hours per session, 3 to 4 times/week, using the 5008 High-Volume HDF Machine from Fresenius Medical Care with High Flux FX1000 Dialyzer (Mode pre-dilution HDF).	Device: Online Pre-dilution Hemodiafiltration; The following parameters: maximum Blood flow rate allowed by vascular access, dialyste rate of 500 mL/min and average convective volume of >44L/session reinjected in pre-dilution mode. The dialysate composition, net ultrafiltration rate and use of anticoagulation will be prescribed according to participant's characteristics.
Experimental: Post-dilution Hemodiafiltration; Participants will receive intermittent post-dilution HDF for a minimum of 4hours per session, 3 to 4 times/week, using the 5008 High-Volume HDF Machine from Fresenius Medical Care with High Flux FX1000 Dialyzer (Mode post-dilution HDF).	Device: Online Post-dilution Hemodiafiltration; The following parameters: maximum Blood flow rate allowed by vascular access, dialyste rate of 500 mL/min and average convective volume of >22L/session reinjected in pre-dilution mode. The dialysate composition and net ultrafiltration rate will be prescribed according to participant's characteristics. Usage of intra-dialysis anticoagulation is mandatory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protocol adherence (feasibility)	If ≥85% of overall dialysis sessions are administered per-protocol according to the allocated modality	90 days
Adherence to follow-up (feasibility)	If it was possible to obtain end-of-study outcomes in ≥90% of participants	90 days
Participant accrual (feasibility)	If the average monthly enrolment is 4 or more participants per months	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	(overall mortality)	30 days
Mortality	(overall mortality)	90 days
End-of-study eGFR	(mL/min/1.73m2)	90 days
Dialysis dependence	Defined as the receipt of dialysis at day 90	90 days
Total number of days on dialysis	(in patients with renal recovery)	90 days
Length of hospitalisation stay	(days)	90 days
Number of patients with hemodynamic instability during dialysis treatment (first week)	(using two definitions): Defined as systolic blood pressure drop <90 mmHg requiring intervention (one of the following: increase of vasopressor, Ultrafiltration cessation/reduction, termination of the dialysis session or fluid bolus); Variations in the vasoactive-inotropic score between pre-dialysis and per-dialysis timepoint	7 days
Number of dialysis session complicated by Circuit/filter clotting	(proportion)	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Exploratory) Inflammatory serum biomarkers modulation	(Percentage of reduction by clearance of the following biomarkers: C-reactive protein, CCL11, CCL26, Fibroblast growth Factor, GM-CSF, ICAM-1, IFN-γ, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-1α, IL-1β, IL 2, IL-4, IL-5, IL-6, IL-7, CXCL8, CXCL10, CCL2, CCL3, CCL4, CCL13, CCL22, Placental growth factor, Serum Amyloid A, CCL17, Tyrosine kinase 2 (Tie)-2, TNF-α, TNF-β, VCAM-1 and VEGF)	Day 0 and Day 7
(Exploratory) Phenotype of circulation neutrophils	Activation phenotype of circulating neutrophils, using variation in the mean fluorescent intensity (MFI) by flux-cytometry, measured at randomisation (Day0) and after first week of treatment (Day7)	Day 0 and Day 7
(Exploratory) Phenotype of circulation monocytes	Activation phenotype of circulating monocytes, using variation in the mean fluorescent intensity (MFI) by flux-cytometry, measured at randomisation (Day0) and after first week of treatment (Day7)	Day 0 and Day 7

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Investigators: Principal Investigator: Jean-Maxime Cote, MD, MSc, CHUM

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): November 30, 2024
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Renal replacement therapy; hemodialysis; Acute kidney injury; hemodiafiltration; AKI
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury; Wounds and Injuries
• Other Study ID Numbers: 20.147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No