I.D.E.A.L.-I.C.U. (Initiation of Dialysis EArly Versus deLayed in Intensive Care Unit)

Study Overview
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Brief Summary
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The purpose of this multicentric, randomized controlled trial is to assess whether the timing of renal replacement therapy initiation (early vs delayed) has an impact on mortality at 90 days in patients with severe acute kidney injury at the failure stage (according to RIFLE criteria) during the initial phase of septic shock.

Detailed Description
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Acute renal failure is one of the most feared complications of septic shock and occurs in 51% of patients with these conditions. Mortality at 3 months ranges from 36% to 60%. To date, these exists no consensus regarding the optimal time to initiate renal remplacement therapy (RRT). Retrospective and observational studies have suggested that early initiation of RRT could help to improve prognosis in these patients. Therefore, we aim to investigate wether early initiation of RRT (within 12 hours after a diagnosis of acute renal insufficiency at the failure stage according to the RIFLE Criteria), will reduce 90-day mortality as compared to deferred initiation of RRT (48 to 60 hours after diagnosis), in intensive care unit (ICU) patients with septic shock who develop acute renal failure. Secondary objectives include: to compare the impact of the two RRT strategies on 28, 180 et 360 day mortality, duration of mechanical ventilation, duration of RRT, duration of ICU stay and duration of overall hospital stay. In addition, quality of life at 90 and 360 days will be evaluated using the EQ5D questionnaire. Tolerance of both strategies will be compared in terms of metabolic disorders, arrhythmias, pulmonary oedema by overload, hypotension, hemorrhagic complications, and dependence on RRT at hospital discharge.

Official Title
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Impact on Mortality of the Timing of Renal Replacement Therapy in Patients With Severe Acute Kidney Injury in Septic Shock: the IDEAL-ICU Study (Initiation of Dialysis Early Versus Delayed in the Intensive Care Unit): Study Protocol for a Randomized Controlled Trial

Conditions
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Septic Shock, Acute Renal Failure (as Defined by the Failure Stage of the RIFLE Classification)

Intervention / Treatment
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* Procedure: Renal Remplacement Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (males or females, age >18 years) with septic shock who develop acute renal failure (as defined by the Failure stage of the RIFLE classification) will be eligible for inclusion. Septic shock is defined as severe sepsis with at least 2 to 4 SIRS criteria and persistent hypotension despite adequate vascular filling and need vaso-active drugs. SIRS is defined as the simultaneous presence of at least 2 of the following criteria : Body temperature ≥ 38°C ou ≤ 36°C Heart rate ≥ 90 bpm Respiratory rate ≥ 20/mn or PaCO2 ≤ 32 mmHg Leucocytes ≥ 12,000/mm3 or ≤ 4,000/mm3 or >10% immature forms. Acute renal insufficiency is defined as the failure stage of the RIFLE classification, i.e. the presence of at least one of the following criteria: Increased creatinine x 3 times the baseline value Oliguria < 0.3 ml/kg/h for 12 hours Anuria (diuresis < 100ml) for at least 12 hours All patients are required to provide informed consent after having been appropriately informed about the study. In case of temporary incapacity of the patient to sign, the consent form can be signed by a surrogate. Exclusion Criteria: Patients presenting any of the following criteria will not be eligible for inclusion in the study: Patients with chronic renal at dialysis. Patients presenting acute renal failure of type obstructive and patients already presenting emergency criteria for immediate hemodialysis at the time of randomization (i.e. hyperkalemia >6.5 mmol/L or pH<7.15 or pulmonary oedema by fluid overload) Patients already had hemodialysis before their arrival in the intensive care unit Pregnant women. Moribund patients whose life expectancy is less than 24 hours Patients unlikely to survive to 28 days because of uncontrollable comorbidities (e.g. cardiac, pulmonary or hepatic disease at the terminal stage, hepatorenal syndrome, uncontrolled cancer, severe post-anorexic encephalopathy…) Patients with advance directives indicating their wish not to be resuscitated. Patients under legal guardianship. Patients participing in another interventional study that may influence the prognosis of patients.

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
Interventional Model Description: To investigate whether early initiation of RRT (within 12 hours after a diagnosis of acute renal insufficiency at thefailure stage according to the RIFLE Criteria), will reduce 90-day mortality as compared to deferred initiation of RRT(48 to 60 hours after diagnosis), in intensive care unit (ICU) patients with septic shock who develop acute renal failure
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early initiation of RRT<br>Start of RRT within a maximum of 12 hours after randomisation. | Procedure: Renal Remplacement Therapy<br>* Investigators of each center will have the choice of the RRT technique based on their usual practice: intermittent hemodialysis, intermittent hemodiafiltration, continuous hemodialysis, continuous hemofiltration, continuous hemodiafiltration (typically the continuous techniques in the acute phase, followed by intermittent techniques after stabilization). In case of life threatening conditions within the 48 hours after randomisation (hyperkalemia, metabolic acidosis or pulmonary edema) the RRT will be initiated as soon as possible. In case of improvement of renal function within the 48 hours after randomisation (defined as the return of spontaneous urine output > 1000ml/24 hr or >2000ml/24hr with diuretics), RRT is not mandatory.<br>|
| Active Comparator: Deferred RRT<br>Start of RRT between 48 and 60 hours after randomisation. | Procedure: Renal Remplacement Therapy<br>* Investigators of each center will have the choice of the RRT technique based on their usual practice: intermittent hemodialysis, intermittent hemodiafiltration, continuous hemodialysis, continuous hemofiltration, continuous hemodiafiltration (typically the continuous techniques in the acute phase, followed by intermittent techniques after stabilization). In case of life threatening conditions within the 48 hours after randomisation (hyperkalemia, metabolic acidosis or pulmonary edema) the RRT will be initiated as soon as possible. In case of improvement of renal function within the 48 hours after randomisation (defined as the return of spontaneous urine output > 1000ml/24 hr or >2000ml/24hr with diuretics), RRT is not mandatory.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | To investigate whether early initiation of RRT (within 12 hours after a diagnosis of acute renal insufficiency at the failure stage according to the RIFLE Criteria), will reduce 90-day mortality as compared to deferred initiation of RRT (48 to 60 hours after diagnosis), in intensive care unit (ICU) patients with septic shock who develop acute renal failure. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the tolerance and evaluation quality of life | Secondary objectives include: to compare the impact of the two RRT strategies on 28, 180 and 360 day mortality, duration of mechanical ventilation, duration of RRT, duration of ICU stay and duration of overall hospital stay. In addition, quality of life at 90 and 360 days will be evaluated using the EQ5D questionnaire. Tolerance of both strategies will be compared in terms of metabolic disorders, arrhythmias, pulmonary oedema by overload, hypotension, hemorrhagic complications, and dependence on RRT at hospital discharge. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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septic shock; acute renal failure; renal remplacement therapy; mortality; intensive care; critical care; acute kidney injury