Online Hemodiafiltration vs Conventional Hemodialysis for Acute Kidney Injury

(HDFAKI Trial)

Recruiting at 1 trial location

Overseen By William Beaubien-Souligny, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Immunosuppressants

Disqualifiers: Pregnancy, Chronic dialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests treatments for people with severe kidney problems in the ICU. It compares two types of hemodiafiltration (a kidney treatment that filters the blood) with regular hemodialysis to determine which method better reduces inflammation and improves kidney recovery. Participants suitable for this trial have severe kidney injury and are already receiving kidney treatment in the ICU. As an unphased trial, it offers patients the chance to contribute to important research that could enhance future kidney treatments.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on active immunosuppressive therapy, you are excluded from participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that online hemodiafiltration, a type of blood filtering treatment, is likely safe for patients. Studies tested two methods: post-dilution and pre-dilution hemodiafiltration. Post-dilution hemodiafiltration has been linked to a lower risk of death in patients needing kidney treatment, indicating it is well-tolerated. Similarly, pre-dilution hemodiafiltration has demonstrated better survival rates compared to regular hemodialysis, suggesting it is also safe.

While these results are promising, this treatment is not yet commonly used for sudden kidney problems, so more research is needed to understand its safety fully. Overall, current evidence suggests these treatments are generally safe for people who need kidney support. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about exploring different hemodiafiltration techniques for treating acute kidney injury because these methods could enhance the efficiency of dialysis. Unlike conventional hemodialysis, which primarily filters toxins from the blood, post-dilution and pre-dilution hemodiafiltration might improve toxin removal by using a combination of diffusion and convection processes. This could potentially lead to better outcomes for patients by more effectively clearing larger molecules from the blood. Additionally, these techniques aim to optimize fluid balance, which is a crucial factor in managing acute kidney injury and improving patient recovery.

What evidence suggests that this trial's treatments could be effective for acute kidney injury?

This trial will compare different dialysis methods for acute kidney injury. Research has shown that high-efficiency post-dilution online hemodiafiltration (HDF), one of the treatments in this trial, might lower the risk of death from any cause in people with kidney problems. This treatment cleans the blood using both convection and diffusion. Another treatment option in this trial, pre-dilution HDF, has studies suggesting it could improve survival rates compared to regular dialysis. Some research indicates it might help kidneys recover and reduce death rates in patients with acute kidney injury (AKI). Although specific data for AKI is limited, HDF appears promising in improving patient outcomes compared to standard hemodialysis, which is also being tested in this trial. ^{1 3 4 6 7}

Who Is on the Research Team?

Jean-Maxime Cote, MD, MSc

Principal Investigator

CHUM

Are You a Good Fit for This Trial?

This trial is for adults over 18 in the ICU with severe acute kidney injury needing renal replacement therapy, not on chronic dialysis or immunosuppressive drugs, and not pregnant. They must be able to consent and not involved in other dialysis studies.

Inclusion Criteria

I am currently in the intensive care unit.

I need dialysis for acute kidney injury as decided by my doctor.

I have severe kidney injury.

Exclusion Criteria

You are already taking part in another study about dialysis treatments.

Subjects or relatives/next-of-kin unable to provide written informed consent

I am not pregnant, breastfeeding, or planning to become pregnant during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either post-dilution or pre-dilution hemodiafiltration, or conventional hemodialysis, 3 to 4 times per week for a minimum of 4 hours per session

4 weeks

3-4 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of inflammatory biomarkers and renal recovery

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Conventional Hemodialysis
• Online Post-dilution Hemodiafiltration
• Online Pre-dilution Hemodiafiltration

Trial Overview The study tests if Online Hemodiafiltration (pre-dilution or post-dilution) can reduce inflammation and improve kidney recovery compared to Conventional Hemodialysis in ICU patients with acute kidney injury.

How Is the Trial Designed?

Group I: Pre-dilution Hemodiafiltration Experimental Treatment 1 Intervention

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).

Group II: Post-dilution Hemodiafiltration Experimental Treatment 1 Intervention

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).

Group III: Conventional Hemodialysis Active Control 1 Intervention

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).

Conventional Hemodialysis is already approved in United States, European Union for the following indications:

Approved in United States as Conventional Hemodialysis for:

• End-stage kidney disease
• Chronic kidney disease progressing to dialysis-dependent kidney disease

Approved in European Union as Conventional Hemodialysis for:

• End-stage kidney disease
• Chronic kidney disease progressing to dialysis-dependent kidney disease

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Published Research Related to This Trial

High volume post-dilution hemodiafiltration may lead to lower death rates compared to conventional hemodialysis, as suggested by post-hoc analyses of previous trials.

The study aims to determine whether the benefits of high volume hemodiafiltration are due to the convection volume achieved or the duration of dialysis required to reach these high volumes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High volume online post-dilution hemodiafiltration: how relevant is it in chronic kidney disease? Castro, MCM.[2022]

A study involving 10,000 patients (5,000 pairs) found that predilution on-line hemodiafiltration is associated with improved overall survival compared to conventional hemodialysis, with a hazard ratio of 0.83 for all-cause mortality.

Patients receiving higher substitution volumes (≥40.0 L per session) during predilution on-line hemodiafiltration showed even better survival rates, suggesting that optimizing substitution volume may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predilution online hemodiafiltration is associated with improved survival compared with hemodialysis. Kikuchi, K., Hamano, T., Wada, A., et al.[2020]

A pilot study involving 51 patients assessed the feasibility and safety of incremental-start hemodialysis (HD), showing high adherence rates (96%) to the treatment schedule and successful enrollment in a randomized study.

Patients in the incremental HD group experienced less decline in urine volume and solute clearance compared to those receiving conventional thrice-weekly HD, suggesting potential benefits of this approach, although further research with larger trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-Weekly Hemodialysis With Adjuvant Pharmacotherapy and Transition to Thrice-Weekly Hemodialysis: A Pilot Study. Murea, M., Patel, A., Highland, BR., et al.[2023]

The HOLLANT study is a multicenter trial involving 40 dialysis patients, designed to investigate whether high-volume online hemodiafiltration (HV-HDF) reduces the incidence of intradialytic hypotension (IDH), which may contribute to better overall and cardiovascular survival compared to standard hemodialysis.

The study will assess various outcomes, including blood pressure changes, heart function, organ damage, and patient-reported symptoms, to understand the mechanisms behind the potential benefits of HV-HDF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of various dialysis modalities on intradialytic hemodynamics, tissue injury and patient discomfort in chronic dialysis patients: design of a randomized cross-over study (HOLLANT). Rootjes, PA., Nubé, MJ., de Roij van Zuijdewijn, CLM., et al.[2022]

Postdilution online hemodiafiltration (HDF) has been clinically established as beneficial, leading to a significant increase in its use in Japan, where it accounted for 10% of the dialysis population by the end of 2013.

In Japan, predilution online HDF is predominantly used (90.8% of cases) due to lower blood flow rates, which allows for reduced albumin loss and less membrane fouling, although there is currently insufficient evidence to support its clinical advantages over conventional hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Expectation of Online Hemodiafiltration: A Japanese Perspective. Akizawa, T., Koiwa, F.[2015]

A new simple mid-dilution OL-HDF technique was tested on 12 stable end-stage renal disease patients, showing high efficiency in clearing uremic toxins while minimizing protein loss.

This method combines the benefits of both pre- and post-dilution modes of hemodiafiltration, potentially reducing morbidity and mortality in hemodialysis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A simple efficient technique of 'mid-dilution' on-line hemodiafiltration. Susantitaphong, P., Tiranathanagul, K., Hanvivatvong, O., et al.[2016]

Online hemodiafiltration (OL-HDF) is associated with a reduced risk of mortality compared to standard hemodialysis, making it a recommended first-line treatment for hemodialysis patients.

To maximize the benefits of OL-HDF, it is advised to achieve a convective volume greater than 23 liters per session, using the highest possible blood flow and infusion rates, although there is no evidence to support normalizing the convective dose to body size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is There an 'Optimal Dose' of Hemodiafiltration? Maduell, F.[2015]

Predilution on-line hemodiafiltration (OL-HDF) is preferred in Japan for its ability to increase substitution volume at lower blood flow rates and effectively remove larger low-molecular-weight proteins, potentially improving patient outcomes.

Recent studies indicate that predilution OL-HDF may offer significant survival benefits, particularly in reducing all-cause and cardiovascular mortality, while also maintaining hemodynamic stability compared to postdilution methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for the Clinical Advantages of Predilution On-Line Hemodiafiltration. Masakane, I., Kikuchi, K., Kawanishi, H.[2018]

Citations

1. journals.lww.com journals.lww.com/sjkd/fulltext/2022/33050/intermittent_online_postdilution_hemodiafiltration.8.aspx

Intermittent Online Postdilution Hemodiafiltration versus... In this study, we compared intermittent online postdilution HDF with the standard high-flux (HF) intermittent HD in non-critically ill patients with community- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04525092

Online Hemodiafiltration vs Conventional Hemodialysis in ... 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37955459/

Intermittent Online Postdilution Hemodiafiltration versus ... Several studies have used predilution hemodiafiltration (HDF) in critically ill AKI patients with mixed results. In this study, we compared ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2304820

Effect of Hemodiafiltration or Hemodialysis on Mortality in ... High-efficiency postdilution online hemodiafiltration reduces all-cause mortality in hemodialysis patients. J Am Soc Nephrol 2013;24:487-497. Crossref.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12295283/

Why High-Volume Post-Dilution Hemodiafiltration Should Be ... According to the United States Renal Data System 2024 Annual Data Report, the all-cause mortality rate among HD patients in 2022 was 145.6 per 1000 person-years ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9751768/

Online Hemodiafiltration Compared to Conventional ... We aimed to determine whether the use of HDF in acute kidney injury (AKI) is associated with lower mortality and improved kidney recovery up to 90 days after ...

7. mdpi.com mdpi.com/2077-0383/14/14/4860

Why High-Volume Post-Dilution Hemodiafiltration Should ... According to the United States Renal Data System 2024 Annual Data Report, the all-cause mortality rate among HD patients in 2022 was 145.6 per 1000 person-years ...