Online Hemodiafiltration vs Conventional Hemodialysis in Acute Kidney Injury

Acute Kidney Injury Clinical Trial

— HDFAKI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04525092
• Other study ID #: 20.147
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2021
• Est. completion date: March 2024

Study information

• Verified date: March 2023
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: Jean Maxime Cote, MD, MSc
• Phone: 514 890 8000
• Email: jean-maxime.cote[@]umontreal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: March 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Wounds and Injuries

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Canada	Centre de recherche du CHUM	Montreal	Quebec
Ireland	Clinical Research Centre University College Dublin	Dublin

Sponsors (1)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)

Countries where clinical trial is conducted

Canada,  Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	(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-?, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-1a, IL-1ß, 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-a, TNF-ß, VCAM-1 and VEGF)	Day 0 and Day 7
Other	(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
Other	(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
Primary	Protocol adherence (feasibility)	If =85% of overall dialysis sessions are administered per-protocol according to the allocated modality	90 days
Primary	Adherence to follow-up (feasibility)	If it was possible to obtain end-of-study outcomes in =90% of participants	90 days
Primary	Participant accrual (feasibility)	If the average monthly enrolment is 4 or more participants per months	90 days
Secondary	Mortality	(overall mortality)	30 days
Secondary	Mortality	(overall mortality)	90 days
Secondary	End-of-study eGFR	(mL/min/1.73m2)	90 days
Secondary	Dialysis dependence	Defined as the receipt of dialysis at day 90	90 days
Secondary	Total number of days on dialysis	(in patients with renal recovery)	90 days
Secondary	Length of hospitalisation stay	(days)	90 days
Secondary	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
Secondary	Number of dialysis session complicated by Circuit/filter clotting	(proportion)	90 days