Continuous Veno-venous Hemodialysis and Continuous Veno-venous Hemodiafiltration on Urea Reduction Rate in Intensive Care Patient

Official title

Comparison of the Effectiveness of Continuous Veno-venous Hemodialysis and Continuous Veno-venous Hemodiafiltration on Urea Reduction Rate in Intensive Care Patients With Acute Renal Injury : a Monocentric Controled Randomized Non Inferiority Open Labeled Study

Overview

In patients requiring renal replacement therapy (RRT) in the intensive care unit (ICU), continuous techniques are predominantly using due to better hemodynamic tolerance. The most employed techniques in ICU are continuous venovenous hemodiafiltration (CVVHDF) and continuous venovenous hemodialysis (CVVHD). To our knowledge, there are no prospective studies comparing the efficiency of these two techniques with the same dose of dialysis (and the same filter). In the CompEER study, we aim to compare the efficiency of CVVHD and CVVHDF on urea reduction rate in intensive care patients with acute kidney injury. The research hypothesis is that CVVHD citrate technique is as effective as CVVHDF heparin technique for urea reduction and provides prolonged and stable clearance, facilitating antibiotic management during RRT.

Detailed description

Acute Kidney Injury (AKI) is found in more than 50% of intensive care unit (ICU) patients, with 30% classified as AKI Network (AKIN) stage 3. Approximately 23% of AKI patients undergo RRT, predominantly utilizing continuous techniques due to better hemodynamic tolerance in unstable patients. Common continuous RRT techniques include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF).

The two most employed techniques in ICU are CVVHDF and CVVHD. However, the choice often depends on institutional practices rather than scientific evidence. Limited studies comparing these techniques at equivalent doses exist, and French recommendations allow intensivists discretion based on availability and team experience. A small, randomized study comparing different exchange rates found higher urea reduction in CVVHDF but lacked statistical significance. Current practices in ICU involve using CVVHDF with systemic anticoagulation or CVVHD with regional citrate anticoagulation based on practitioner preferences.

Despite potential benefits of CVVHD with citrate, such as extended filter lifespan and stable dialysis dose, the impact on concomitant treatments, especially antibiotics, needs consideration.

The study aims to demonstrate the non-inferiority of citrate-based continuous hemodialysis (CVVHD) compared to heparin-based continuous hemodiafiltration (CVVHDF) in terms of urea reduction rate at 24 hours in AKI patients requiring renal replacement therapy.

The hypothesis is that CVVHD citrate is as effective as CVVHDF heparin, providing prolonged and stable clearance, facilitating antibiotic management during RRT.

Interventions

• Other CVVHD Dialysis parameters
  Patients will receive a CVVHD dialysis with a dose of 25ml/kg/h dialysate (100% dialysate), with Fresenius Medical Care multiFiltrate PRO kit and Ultraflux AV1000S filter (polysuflone 1.8m²).Regional anticoagulation with citrate
• Other CVVHDF Dialysis parameters
  Patients will receive a CVVHDF dialysis with a dose of 25ml/kg/h dialysate (50% ultrafiltration, 50% dialysate), with Fresenius Medical Care multiFiltrate PRO kit and Ultraflux AV1000S filter (polysuflone 1.8m²). Systemic anticoagulation with heparine

Primary outcome measures

• urea reduction rate (URR) [Time frame: 24 hours]

Secondary outcome measures (11)

• Creatinine clearance at H24 [Time frame: 24 hours]
• Urea clearance at H24 [Time frame: 24 hours]
• Urea clearance at H48 [Time frame: 48 hours]
• ICU Mortality [Time frame: End of ICU Stay]
• Mortality at Day 28 [Time frame: Day 28]
• Organ failure-free days at Day 28 [Time frame: Day 28]
• Hypokalemia at Day 28 [Time frame: Day 28]
• Hypophosphatemia at Day 28 [Time frame: Day 28]
• Hypomagnesemia at Day 28 [Time frame: Day 28]
• Hyperkalemia at Day 28 [Time frame: Day 28]
• Medical Cost [Time frame: 24 hours]

Eligibility criteria

Inclusion criteria

• Adult patients hospitalized in ICU
• Undergo RRT session because of AKI stage 3
• At least one among criteria: pH < 7,20 / Blood urea > 30mM / Fluid overload uncontrolled by with PaCO₂ < 35 mmHg or mixed acidosis with PaCO₂ < 50 mmHg.

• Oliguria lasting 72 hours or longer
• Patients undergoing their first session of extracorporeal blood purification, initiated less than 12 hours prior to randomization
• Patient having given free and informed consent, and having signed the consent form or patient included in an emergency situation
• Patient affiliated with Social Security.

Exclusion criteria

• End-stage chronic kidney disease on dialysis
• Intoxication with a dialyzable toxin (lithium
• Criteria for emergency dialysis initiation: hyperkaliemia >6,5mM with electrocardiographic signs
• Medical contraindication to regional citrate: severe liver failure
• Medical contraindication to anticoagulation or heparin anticoagulation: heparin induced thrombopenia or uncontrolled bleeding
• Pregnant women, parturient or breast-feeding patient

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• CHU de Nimes — Nîmes

Publications

• Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Au PMID 26162677
• Joannes-Boyau O, Honore PM, Perez P, Bagshaw SM, Grand H, Canivet JL, Dewitte A, Flamens C, Pujol W, Grandoulier AS, Fleureau C, Jacobs R, Broux C, Floch H, Branchard O, Franck S, Roze H, Collin V, Boer W, Calderon J, Gauche B, Spapen HD, Janvier G, Ouattara A. High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre random PMID 23740278
• Vinsonneau C, Allain-Launay E, Blayau C, Darmon M, Ducheyron D, Gaillot T, Honore PM, Javouhey E, Krummel T, Lahoche A, Letacon S, Legrand M, Monchi M, Ridel C, Robert R, Schortgen F, Souweine B, Vaillant P, Velly L, Osman D, Van Vong L. Renal replacement therapy in adult and pediatric intensive care : Recommendations by an expert panel from the French Intensive Care Society (SRLF) with the French PMID 26714808
• Guilhaumou R, Benaboud S, Bennis Y, Dahyot-Fizelier C, Dailly E, Gandia P, Goutelle S, Lefeuvre S, Mongardon N, Roger C, Scala-Bertola J, Lemaitre F, Garnier M. Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics (Societe Francaise de Pharmacologie et Therapeutique-SFPT) and the French Society of PMID 30925922
• Zarbock A, Kullmar M, Kindgen-Milles D, Wempe C, Gerss J, Brandenburger T, Dimski T, Tyczynski B, Jahn M, Mulling N, Mehrlander M, Rosenberger P, Marx G, Simon TP, Jaschinski U, Deetjen P, Putensen C, Schewe JC, Kluge S, Jarczak D, Slowinski T, Bodenstein M, Meybohm P, Wirtz S, Moerer O, Kortgen A, Simon P, Bagshaw SM, Kellum JA, Meersch M; RICH Investigators and the Sepnet Trial Group. Effect of PMID 33095849

Identifiers

NCT: NCT06369064 · 2023A02707-38

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗