Early Deresuscitation Strategy Driven by Tissue Perfusion in Renal Replacement Therapy in Patients With Acute Renal Failure

Study Overview
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Brief Summary
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In Intensive Care Unit (ICU) patients with acute kidney injury (AKI) and treated with renal replacement therapy (RRT) often present a fluid overload which is associated with morbidity (mechanical ventilation duration increase, kidney recovery decrease) and mortality. Patients' prognostic could be improved by correcting the fluid overload with net ultrafiltration (UFnet) however it may lead to harmful iatrogenic hypovolemia responsible of deleterious ischemic lesions. In usual practice, UF net prescription are variable and there are different international recommendations. Some observational studies suggest that using a UFnet between 1 et 1.75 mL/kg/h in fluid overloaded patient decrease mortality. Fluid overload increases morbidity and mortality, particularly in RRT. Studies without RRT argue for an efficacy of management by decreasing the fluid overload .Cohort studies suggest to use a moderate UFnet instead of a low UFnet. Some data from studies on early versus late RRT that relate the fluid balance or correct the fluid overload during the early strategy argue for a beneficial effect of an early deresuscitation strategy Consequently, the impact of a moderate UFnet (to decrease the fluid overload) compared to a low UFnet (to stabilize the fluid overload) in a randomized interventional study could be assessed. The study hypothesis is that : an early fluid overload deresuscitation protocol with a high UFnet (2 ml/kg/h) targeting both the negativation of cumulated fluid balance to reach a dry weight and the maintenance of tissue perfusion. Compared to fluid overload deresuscitation protocol with a low UFnet (between 0 and 1 ml/kg/h) to reach a stabilization of cumulated fluid balance without monitoring the tissue perfusion. could improve overall, renal, hemodynamic and respiratory prognosis in fluid overloaded patients with renal replacement therapy in ICU

Official Title
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Early Deresuscitation Strategy Driven by Tissue Perfusion in Renal Replacement Therapy in Patients With Acute Renal Failure in Intensive Care Unit. A Randomized Study

Conditions
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Acute Kidney Injury, Fluid Overload

Intervention / Treatment
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* Procedure: Fluid balance negativation
* Procedure: Body weight Stabilization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute kidney injury treated by continuous renal replacement therapy in ICU less than 7 days, At least 1 organ failure during ICU in addition to AKI (mechanical ventilation or vasopressors administration>12 hours), Cumulative UF net less than 1000ml before inclusion, Norepinephrine < 0,5 µg/kg/min, Absence of hypoperfusion signs, Fluid overload defined as follows : fluid overload > 5% of base weight (based on cumulative fluid balance or a weight gain) and/or peripheral edema (AKIKI edema scale > 2). Exclusion Criteria: Chronic renal failure hemodialyzed before admission to the ICU, Mechanical circulatory support (ECMO, LVAD), Pregnant, child -bearing age or lactating women, Stroke less than 30 days, Intestinal ischemia less than 7 days documented non-operated, Interventional study participation or exclusion period on going, Guardianship, curatorship or safeguard of justice, Absence of signature of free and informed consent by the patient and/or relative, Patients not affiliated to a social security scheme or beneficiaries of a similar scheme

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Corrective strategy<br>In the experimental group, all patients will have a UFnet settled (2 ml/kg/h ) in order to reach the patient baseline body weight. | Procedure: Fluid balance negativation<br>* During the RRT, UFnet will be settled on 2ml/kg/h and adapted to hemodynamic tolerance and tissue perfusion . When the patient's baseline body weight is reached the UF net will be settled to maintain it. In case of failure of the fluid balance negativation after 24h, UFnet will be settled on 3ml/kg/h. Then when the baseline body weight is reached UFnet will be settled on 0.5 et 1ml/kg/h or if necessary adapted to 1,5ml/kg/h to maintain it In case of hemodynamic intolerance (NADN > 0,5 µg/kg/min) or tissue hypoperfusion, UF net will be stopped during 6 hours and restarted if NADN < 0,5 µg/kg/min and without tissue hypoperfusion.<br>|
| Other: Stabilizing strategy<br>In the control group, all patients will have a UFnet 2 ml settled (0 to 1 ml/kg/h) in order to stabilize the patient body weight. | Procedure: Body weight Stabilization<br>* During the RRT, UFnet will be settled between 0 et 1 ml/kg/h and adapted in case of weight stabilization failure or hemodynamic intolerance. In case of weight stabilisation failure ( variation >5%), the UF net can be increased to 1,5 ml/kg/h. In case of hemodynamic intolerance (NADN > 0,5 µg/kg/min), UF net will be stopped during 6 hours and restarted if NADN < 0,5 µg/kg/min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of organ replacement free-days | Number of organ replacement free-days, i.e, number of renal replacement therapy-free days, number of vasopressor-free days, number of ventilator-free day. Number of days between 2 same type organ replacement interruption is not counted. In case of death before 30 days, number of days is censored to 0. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality decrease | Number of deaths | 30 days | 
| Number of renal replacement therapy-free days increase | Number of renal replacement therapy-free days | Day 30 | 
| Number of ventilator-free day increase | Number of ventilator-free day | Day 30 | 
| Number of vasopressor-free day increase | Number of vasopressor-free day | Day 30 | 
| Duration of intensive care unit stay | Number of days in ICU | Up to Day 30 | 
| SOFA score evolution | SOFA score : Sepsis-related Organ Failure Assessment, min : 0 max : 24 (worse) | From Day 0 up to Day 5 | 
| Incidence of arrhythmias and cardiac conduction disorders in both group | Number of arrhythmias and cardiac conduction disorders occurrence on ECG | From Day 0 up to Day 5 | 
| Incidence of intestinal ischemia in both group | Number of intestinal ischemia on CT scan or endoscopy | From Day 0 to Day 30 | 
| Incidence of strokes | Number of ischemic strokes occurrence on imagery | From Day 0 to Day 30 | 
| Incidence of delirium | Presence of delirium assessed with the CAM ICU scale : positive or negative score. A positive score means presence of delirium | Between Day 0 and Day 5 | 
| Renal recovery assessment | Renal recovery is defined according to MAKE 30 scale : Survival Absence of renal replacement therapy Day 30 creatinine level < baseline creatinine x 200 % | Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Replacement Therapy (RRT), Ultrafiltration, Deresuscitation, Fluid balance, Fluid overload, Tissue perfusion