Acute Kidney Injury
Conditions
Keywords
hemodialysis, hemodiafiltration, Acute kidney injury, AKI, Renal replacement therapy, Inflammation
Brief 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.
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.
Interventions
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.
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.
DEVICEOnline 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.
Sponsors
Centre hospitalier de l'Université de Montréal (CHUM)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pilot, Randomised, Open-label, Parallel Groups (co-intervention, 1:1:1) of three interventions: conventional HD, pre-dilution HDF and post-dilution HDF
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adherence to follow-up (feasibility) | 90 days | If it was possible to obtain end-of-study outcomes in ≥90% of participants |
| Participant accrual (feasibility) | 90 days | If the average monthly enrolment is 4 or more participants per months |
| Protocol adherence (feasibility) | 90 days | If ≥85% of overall dialysis sessions are administered per-protocol according to the allocated modality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dialysis dependence | 90 days | Defined as the receipt of dialysis at day 90 |
| Length of hospitalisation stay | 90 days | (days) |
| Number of patients with hemodynamic instability during dialysis treatment (first week) | 7 days | (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 |
| Number of dialysis session complicated by Circuit/filter clotting | 90 days | (proportion) |
| Total number of days on dialysis | 90 days | (in patients with renal recovery) |
| Mortality | 30 days | (overall mortality) |
| End-of-study eGFR | 90 days | (mL/min/1.73m2) |
Other
| Measure | Time frame | Description |
|---|---|---|
| (Exploratory) Inflammatory serum biomarkers modulation | Day 0 and Day 7 | (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) |
| (Exploratory) Phenotype of circulation monocytes | Day 0 and Day 7 | 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) |
| (Exploratory) Phenotype of circulation neutrophils | Day 0 and Day 7 | 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) |
Countries
Canada, Ireland
Outcome results
None listed