Continuous Hemodialysis With an Enhanced Middle Molecule Clearance Membrane

Study Overview
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Brief Summary
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This study aims to demonstrate equivalence in terms of molecule removal between continuous hemodialysis using an enhanced middle molecule clearance membrane(Ultraflux EMiC2) and continuous hemofiltration using a standard membrane (Ultraflux AV1000S) in ICU patients requiring continuous renal replacement therapy.

Detailed Description
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In sepsis, the removal of middle molecular weight molecules such as cytokines (also called blood purification), has shown a great interest in intensive care during the last decades. Indeed, these cytokines are involved in the development of the multi-organ failure syndrome when patients are in septic shock. There is some evidence to suggest that extracorporeal therapies (hemofiltration-hemodialysis)are interesting tools to modulate the inflammatory response and to restore the immune homeostasis. However, hemodialysis using conventional membranes does not allow the removal of middle molecules. Conversely, high-volume hemofiltration is an appropriate therapy but it has a lot of drawbacks due to the high ultrafiltration rates (removal of beneficial small molecules, technical and economical issues due to the use of large amounts of fluid replacement). Finally, high cut-off hemofiltration has been reported to be associated with significant albumin loss. Therefore, continuous enhanced middle molecule clearance hemodialysis could be an interesting alternative, making possible the removal of these middle molecules without significant albumin loss and with some theoretical advantages (reduced cost due to the possibility to produce the dialysate from a water circuit, decreased nursing workload). The aim of this study is to assess the clearances of different kind of molecules (small, middle and large) when continuous enhanced middle molecule clearance hemodialysis is applied to septic patients.

Official Title
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Evaluation of Continuous Hemodialysis With an Enhanced Middle Molecule Clearance Membrane in Intensive Care

Conditions
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Septic Shock

Intervention / Treatment
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* Device: Dialyzer Ultraflux EMiC2
* Device: Dialyzer Ultraflux AV1000S


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged over 18 years. ICU patients with septic shock and AKI requiring continuous renal replacement. Patient able to agree to be enrolled in the study with informed consent. If the patient can not provide consent, only the consent of family members will be sought if they are present and, to default, the opinion of trustworthy person under article L.1111-6 of the French Health Code. If there is no family present, or trustworthy person designated, the subject will not be included in the study. Exclusion Criteria: Pregnancy or lactation. Participation in another research protocol. People particularly vulnerable as defined in Articles L.1121-5, L.1121-6, L.1121-7, L.1121-8 et L.1122-1-2 of the French Health Code.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dialyzer Ultraflux EMiC2<br>Dialyzer Ultraflux EMiC2 used in Continuous Hemodialysis | Device: Dialyzer Ultraflux EMiC2<br>* Dialysate flow rate = 40 ml/kg/h The treatment duration may be variable depending on modifications in patient health status, but will not exceed 3 sessions of 48 hours each.<br>|
| Active Comparator: Dialyzer Ultraflux AV1000S<br>Dialyzer Ultraflux AV1000S used in continuous Hemofiltration | Device: Dialyzer Ultraflux AV1000S<br>* Ultrafiltration flow rate = 40 ml/kg/h The blood flow rate will be adjusted to obtain a filtration fraction of 20%. Reinjection = 100% postdilution. The treatment duration may be variable depending on modifications in patient health status, but will not exceed 3 sessions of 48 hours each.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance of Urea |  | At 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 
| Clearance of creatinine |  | At 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 
| Clearance of total protein |  | At 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 
| Clearance of albumin |  | At 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 
| Clearance of Beta 2-microglobulin |  | At 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 
| Free light chains kappa of Immunoglobulins |  | At 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean arterial pressure |  | Before connecting Patient and at 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 
| vasopressor requirement |  | Before connecting Patient and at 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 
| PaO2 / FiO2 |  | Before connecting Patient and at 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 
| Heart rate |  | Before connecting Patient and at 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 
| Lactate level |  | Before connecting Patient and at 15 minutes, 60 minutes, 4 hours, 12 hours, 24 hours and 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intensive Care Unit, continuous hemodialysis, continuous hemofiltration, High Cut-off membrane, Enhanced middle molecule clearance membrane, Septic shock, Acute kidney injury, Blood purification, Renal replacement therapy