Evaluation of Integrated Versus Parallel Connection for Renal Replacement Therapy in ECMO Patients

Study Overview
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Brief Summary
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Extracorporeal membrane oxygenation (ECMO) is an extra-corporeal assistance used in case of respiratory or circulatory failure. In case of circulatory failure, ECMO is in the veno-arterial configuration (VA-ECMO). VA-ECMO patients are at high risk of developing acute kidney injury (AKI) and renal replacement therapy (RRT) may be needed in 50% of ECMO patients. Although the administration of RRT in ECMO patients has major implications, no specific recommendations are currently available. The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) international conference identified the evaluation of RRT in these ECMO patients as a research priority. In 2023, the two main configurations used to administer RRT in ECMO patients are an independent delivery on a separate vascular access (parallel connection) or an integration of the RRT machine directly into the ECMO circuit (integrated connection). The integrated connection may reduce infectious and bleeding complications associated with the use of a second vascular access. However, it can expose the hemofilter and circuit to excessive positive pressures that can trigger pressure alarms in the RRT machine and expose the patient to a theoretical risk of air embolism or hemolysis. Furthermore, there is currently no robust data comparing the hemofilter lifespan with the parallel or with the integrated connection, although the filter lifespan is a crucial parameter to assess the quality of the RRT delivery in the ICU. The investigators recently performed a survey of practices in this context of ECMO patients. The investigators found that both strategies (parallel and integrated connection) are widely used and can be seen as common patient care. The hypothesis tested in this study is the following: when RRT is integrated to the ECMO circuit, the hemofilter lifespan is non inferior to the one when RRT is delivered on a separate vascular access. Only VA-ECMO patients will be enrolled in this trial.

Official Title
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Evaluation of Integrated Versus Parallel Continuous Renal Replacement Therapy Connection in ECMO Patients: a Randomized Controlled Trial

Conditions
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Venoarterial Extracorporeal Membrane Oxygenation, Renal Replacement Therapy, Acute Kidney Injury

Intervention / Treatment
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* Procedure: Parallel connection
* Procedure: Integrated connection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 18 and 75 years of age Patient on VA-ECMO who requires the initiation of continuous RRT during VA-ECMO treatment Patient with a foreseeable length of stay in intensive care greater than 24 hours Exclusion Criteria: Patient who does not have a vascular capital allowing for the insertion of a new dialysis catheter to administer RRT and therefore cannot be randomized to the parallel connection group Pregnant, parturient, or breastfeeding women Patient deprived of liberty by a judicial or administrative decision Patient under psychiatric care Patient subject to a legal protection measure (guardianship, curators) Patient not affiliated to a social security system Patient participating in another interventional research study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VA-ECMO patients with parallel connection<br>Patients undergoing VA ECMO with indication for concomitant RRT, assigned to parallel connection group. | Procedure: Parallel connection<br>* The RRT machine is connected on a separate vascular access (dialysis catheter).<br>|
| Active Comparator: VA-ECMO patients with integrated connection<br>Patients undergoing VA ECMO with indication for concomitant RRT, assigned to integrated connection group. | Procedure: Integrated connection<br>* A connection of the RRT machine with the input and output lines directly on the ECMO circuit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemofilter change rate | To assess whether integrated RRT connection in VA-ECMO patients results in a non-inferior hemofilter change rate compared to the parallel connection. The hemofilter change rate is defined as the number of hemofilter replacements observed during the period between the start and the end of the RRT session, normalized by the duration of the session. | Duration of RRT associated with VA-ECMO up to 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of early hemofilter thromboses | To assess if the integrated RRT connection is associated with a lower proportion of early hemofilter thromboses compared to the parallel connection: number of early hemofilter thromboses normalized by the number of hemofilters used. Early is defined as < 24 hours of use. | Duration of RRT associated with VA-ECMO up to 60 days | 
| Proportion of hemofilter thromboses | To assess if the integrated RRT connection is associated with a lower proportion of hemofilter thromboses compared to the parallel connection: number of hemofilter thromboses normalized by the number of hemofilters used. | Duration of RRT associated with VA-ECMO up to 60 days | 
| Down-time | To compare the integrated RRT connection to the parallel connection in terms of duration of non-purification periods in relation to the total duration RRT. | Duration of RRT associated with VA-ECMO up to 60 days | 
| Renal function according to KDIGO stage | To assess renal function at hospital discharge or at day 60 after admission. | At hospital discharge up to 60 days after admission | 
| Number of infectious complications | To assess whether the integrated RRT connection reduces the number of infectious complications associated with the use of an additional vascular access. The infection will be defined as catheter-related in case of documented bacteraemia with positive blood cultures with differential time to positivity or positive catheter culture with the same microorganism. | Duration of RRT associated with VA-ECMO up to 60 days | 
| Number of bleeding complications | To assess whether the integrated RRT connection reduces bleeding complications associated with the use of an additional vascular access. The occurrence of a bleeding syndrome is defined as a bleeding requiring transfusion with collection of the number of red blood cells transfused or requiring an invasive procedure (surgery, embolization), and defined or not as related to dialysis catheter placement or RRT connection to VA-ECMO. | Duration of RRT associated with VA-ECMO up to 60 days | 
| Proportion of ECMO circuit thromboses | To assess whether the integrated RRT connection does not expose the ECMO circuit to a higher probability of thrombosis The occurrence of thrombosis on the ECMO circuit is defined as a thrombus on any part of the ECMO circuit requiring a change in the circuit or oxygenator, or on the oxygenator resulting in a deleterious effect on oxygenation, or resulting in significant fibrinolysis | Duration of RRT associated with VA-ECMO up to 60 days | 
| Number of hemolysis | To assess whether the integrated RRT connection does not expose to a higher probability of hemolysis. The occurrence of intravascular hemolysis is defined as the occurrence of significant hemolytic anemia. | Duration of RRT associated with VA-ECMO up to 60 days | 
| Number of air embolism | To assess whether the integrated RRT connection does not expose the patient to a higher probability of air embolism. The occurrence of an air embolism is defined as an embolic event with clinical impact of any kind, This occurence is related or not to the use of the dialysis catheter or the connection of the RRT to the VA-ECMO circuit. | Duration of RRT associated with VA-ECMO up to 60 days | 
| Number of days spent in intensive care unit | To assess whether the integrated RRT connection modifies the intensive care unit length of stay | Duration of RRT associated with VA-ECMO up to 60 days | 
| Death | 30-day mortality | At 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VA-ECMO, RRT, connection, integrated, parallel, hemofilter