Clinical trial NCT01682590: I.D.E.A.L.-I.C.U. (Initiation of Dialysis EArly Versus deLayed in Intensive Care Unit)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Septic Shock
Acute Renal Failure (as Defined by the "Failure" Stage of the RIFLE Classification)
Keywords: septic shock; acute renal failure; renal remplacement therapy; mortality; intensive care; critical care; acute kidney injury
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2012-09-11
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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:

1. Patients with chronic renal at dialysis.
2. 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)
3. Patients already had hemodialysis before their arrival in the intensive care unit
4. Pregnant women.
5. Moribund patients whose life expectancy is less than 24 hours
6. 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...)
7. Patients with advance directives indicating their wish not to be resuscitated.
8. Patients under legal guardianship.
9. Patients participing in another interventional study that may influence the prognosis of patients.

Primary outcomes:
measure: Progression free survival
timeFrame: 90 days
Secondary outcomes:
measure: Comparison of the tolerance and evaluation quality of life
timeFrame: 90 days
Other outcomes:
Locations:
city: Avignon
country: France
facility: CH Avignon
city: Belfort
country: France
facility: CH Belfort
city: Besançon
country: France
facility: CHU Besançon
city: Bourg-en-Bresse
country: France
facility: CH de BOURG-EN-BRESSE
city: Caen
country: France
facility: CHU Caen
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Dieppe
country: France
facility: CH Dieppe
city: Dijon
country: France
facility: CHU Dijon
city: Etampes
country: France
facility: CH Sud Essonne - Site Etampes
city: Garches
country: France
facility: Hôpital Raymond-Poincaré GARCHES (AP-HP)
city: Grenoble
country: France
facility: CHU Grenoble
city: La Roche sur Yon
country: France
facility: CH de LA ROCHE sur YON
city: Lille
country: France
facility: Groupe Hospitalier de l'institut Catholique de LILLE
city: Lyon
country: France
facility: CHU de Lyon
city: Montpellier
country: France
facility: CHU Montpellier
city: Montpellier
country: France
facility: CHU Lapeyronie
city: Mulhouse
country: France
facility: CHG Mulhouse
city: Nancy
country: France
facility: CHU Nancy Brabois
city: Nîmes
country: France
facility: CHU Nîmes
city: Orleans
country: France
facility: CHR d'Orléans
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: HOPITAL BICHAT Claude-Bernard
city: Pierre-Bénite
country: France
facility: CHU Lyon Sud
city: Périgueux
country: France
facility: CH Périgueux
city: Strasbourg
country: France
facility: CHU de Strasbourg - Nouvel hôpital civil
city: Thionville
country: France
facility: CHR Metz
city: Tours
country: France
facility: CHRU Tours
Study officials:
affiliation: Centre Hospitalier Universitaire Dijon
name: Jean-Pierre QUENOT
role: STUDY_DIRECTOR
affiliation: CHU de Nimes
name: Saber Davide BARBAR
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barbar SD, Binquet C, Monchi M, Bruyere R, Quenot JP. 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. Trials. 2014 Jul 7;15:270. doi: 10.1186/1745-6215-15-270.
citation: Barbar SD, Clere-Jehl R, Bourredjem A, Hernu R, Montini F, Bruyere R, Lebert C, Bohe J, Badie J, Eraldi JP, Rigaud JP, Levy B, Siami S, Louis G, Bouadma L, Constantin JM, Mercier E, Klouche K, du Cheyron D, Piton G, Annane D, Jaber S, van der Linden T, Blasco G, Mira JP, Schwebel C, Chimot L, Guiot P, Nay MA, Meziani F, Helms J, Roger C, Louart B, Trusson R, Dargent A, Binquet C, Quenot JP; IDEAL-ICU Trial Investigators and the CRICS TRIGGERSEP Network. Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis. N Engl J Med. 2018 Oct 11;379(15):1431-1442. doi: 10.1056/NEJMoa1803213.