The Artificial Kidney Initiation in Kidney Injury 2

NCT03396757 | Completed

• 2 other identifiers: K160916J2017-A02382-51
• Study Type: interventional
• Target: 768
• Locations: 2 countries
• Sites: 41

Brief Summary

The timing of renal replacement therapy (RRT) in the context of severe acute kidney injury (AKI) is one the most debated issues in critical care medicine. The Artificial Kidney Initiation in Kidney Injury (AKIKI) was the first large prospective multicenter randomized trial published on this topic. This study (published in the New England Journal of Medicine, July 2017) showed no significant difference between an early and delayed RRT initiation strategy in term of mortality. Nearly 50% of patients escaped RRT in the delayed strategy and this strategy was associated with less catheter-related infections and faster renal function recovery. Two (serum urea concentration \>40 mmol/l and oliguria/anuria for more than 72 hours) of the 5 criteria which mandated RRT in the delayed strategy are still open to debate since they have never been shown to put patient at danger. To go further into our investigation of RRT criteria, the investigators designed a study that would compare the "delayed strategy" used in AKIKI that can now be considered as "standard" with another in which RRT is delayed for a longer period in the absence of a life-threatening complication (such as hyperkalemia or severe overload pulmonary edema).

Conditions

Renal Replacement Therapy for Acute Kidney Injury in ICU

Keywords

Acute Kidney Injury; Critical Care; Renal Replacement Therapy

Outcome Measures

Primary Outcomes (1)

• number of RRT-free days

  One point will be given for each calendar day during the measurement period (i.e. from the first day of randomization to day 28) that a patient was both alive and free of RRT, assuming the patient survives and remains free of RRT for at least 3 consecutive calendar days after RRT weaning, whatever the vital status at day 28. Zero value will be given for patients with RRT initiated the first day of randomization who died before RRT weaning or who remained under RRT until day 28. With this definition, RRT-free days may concern days without RRT both before RRT initiation (a situation encountered by definition in the " delayed strategy" arm) and after RRT weaning (for the two strategies).

  Day 28 after randomization

Secondary Outcomes (41)

• Hydration status (randomization stage)

  Until ICU discharge or day 28 after randomization

• Hydration status (randomization stage)

  Until ICU discharge or day 28 after randomization

• Hydration status (randomization stage)

  Until ICU discharge or day 28 after randomization

• Nutritional status (randomization stage)

  Until ICU discharge or day 28 after randomization

• Nutritional status (randomization stage)

  Until ICU discharge or day 28 after randomization

Study Arms (2)

Standard strategy

ACTIVE COMPARATOR

RRT will be initiated within 12 hours after documentation of serum urea concentration \>40 mmol/l and/or an oliguria/anuria for more than 72 hours (identical to the delayed strategy in AKIKI).

Procedure: Standard strategy

Delayed strategy

EXPERIMENTAL

RRT will be considered only if one potentially severe following situation occurs (noticeable hyperkalemia, or acidosis or pulmonary edema due to fluid overload resulting in severe hypoxemia which do not respond rapidly to medical treatment) or if serum urea concentration reaches 50 mmol/L.

Procedure: Delayed strategy

Interventions

Standard strategy PROCEDURE

RRT is initiated within 12 hours after documentation of serum urea concentration \>40 mmol/l and/or an oliguria/anuria for more than 72 hours. The timing of its initiation will be recorded and RRT will continue until criteria for cessation are observed. This arm corresponds to the "delayed strategy" in the published AKIKI trial (NEJM 2016),

Standard strategy

Delayed strategy PROCEDURE

RRT will be initiated only if one or more of above-mentioned potentially severe situations occur (identical to those used during the observational study) or if serum urea concentration reaches 50 mmol/L (this level being chosen in order to avoid extreme elevations of serum urea levels as mentioned above). The physician in charge will be allowed to try a medical treatment. Patients will not receive RRT whatever the duration of anuria/oliguria if any above-mentioned indication for RRT is not present. When required, RRT will be performed with the same modalities and stopped according to the same criteria as in the "no further delayed" RRT strategy, with special care to avoid dialysis disequilibrium syndrome (see below). The decision to initiate RRT in the "delayed strategy" arm of the trial will have to be approved by the attending physician(s) involved in patient's care in order to make sure that it corresponds to her/his usual practice.

Delayed strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All of the following criteria must be fulfilled to be included in the observational study (first stage):
• Adults (\>18 years)
• Hospitalized in a study ICU.
• Evidence of acute kidney injury compatible with the diagnosis of acute tubular necrosis in a context of ischemic or toxic aggression and who receive (or received for the same episode) invasive mechanical ventilation and/or catecholamine infusion.
• Acute kidney injury stage 3 of KDIGO classification defined by at least one of the following criteria: serum creatinine concentration of more than 4 mg/dl (354 µmol/liter) or greater than 3 times the baseline creatinine level, anuria (urine output of 100 ml/day or less) for more than 12 hours, oliguria (urine output below 0.3 ml/kg/h or below 500 ml/day) for more than 24 hours.
• Oliguria/anuria (urine output \<0.3 ml/kg/h or \<500 ml/day) for more than 72 hours or serum urea concentration comprised between 40 and 50 mmol/l.
• Affiliation to a social security regime

You may not qualify if:

• Severity criteria mandating immediate RRT initiation (Table 1)
• Serum urea level \> 50 mmol/l
• Severe chronic renal failure (defined by a creatinine clearance \< 30 ml/min)
• AKI caused by urinary tract obstruction or renal vessel obstruction or tumour lysis syndrome or thrombotic microangiopathy or acute glomerulopathy
• Poisoning by a dialyzable agent
• Child C liver cirrhosis
• Cardiac arrest without awakening
• Moribund state (patient likely to die within 24h)
• Patient having already received RRT for the current episode of AKI
• Renal transplant
• Treatment limitation (withholding or withdrawal)
• Subject deprived of freedom, subject under a legal protective measure
• Pregnant or breastfeeding woman

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (41)

CH Alès

Alès, France

Location

CHU Amiens

Amiens, France

Location

CH Avignon

Avignon, France

Location

Groupe Hospitalier Carnelle-Portes de l'Oise Site Beaumont / Oise

Beaumont-sur-Oise, France

Location

Hopital Nord Franche Comté - Belfort

Belfort, France

Location

CH Béthune Beuvry - Germont et Gauthier

Béthune, France

Location

CHU Avicenne - APHP

Bobigny, France

Location

CHU Ambroise Paré - APHP

Boulogne-Billancourt, France

Location

CH Bourg en Bresse / Fleyriat

Bourg-en-Bresse, France

Location

Gabriel Montpied - CHU Clermont Ferrand

Clermont-Ferrand, France

Location

CHU Louis Mourier - APHP

Colombes, 92700, France

Location

CH Sud Francilien

Corbeil-Essonnes, France

Location

CHU Henri Mondor - APHP

Créteil, France

Location

CH Dieppe

Dieppe, France

Location

Hôpital François Mitterand - CHU Dijon

Dijon, France

Location

CHD Vendée

La Roche-sur-Yon, 85925, France

Location

CH Le Mans

Le Mans, France

Location

CH Dr Schaffner - Lens

Lens, France

Location

Hôpital Roger Salengro / CHRU Lille

Lille, France

Location

Centre Hospitalier Bretagne sud - Lorient

Lorient, France

Location

GH Edouard Herriot - Lyon

Lyon, France

Location

Hôpital Nord - Anesthésie Réa - APHM

Marseille, France

Location

Hôpital Nord - DRIS - APHM

Marseille, France

Location

La Timone - APHM

Marseille, France

Location

Hopital de Mercy, CHR Metz-Thionville

Metz, France

Location

Hôpital Lapeyronie - CHU Montpellier

Montpellier, France

Location

Hôpital St Eloi - CHU Montpellier

Montpellier, France

Location

Hotel Dieu - Anesthésie Réanimation - CHU Nantes

Nantes, France

Location

Hotel Dieu - Réanimation MIR - CHU Nantes

Nantes, France

Location

Hôpital Nord Laennec - CHU Nantes

Nantes, France

Location

CHU Nimes - Caremeau

Nîmes, France

Location

Chu Hegp - Aphp

Paris, 75015, France

Location

CHU Pitiè Salpêtrière - Pneumologie et réanimation médicale - APHP

Paris, 75015, France

Location

CHU Pitié-Salpêtrière - Réanimation médicale - APHP

Paris, France

Location

CHU Lyon Sud

Pierre-Bénite, France

Location

CHU Poitiers

Poitiers, France

Location

CH René DUBOS

Pontoise, France

Location

CHU Charles Nicolle

Rouen, France

Location

CHU Saint Etienne

Saint-Etienne, France

Location

CH André Mignot

Versailles, France

Location

CHU pointe à Pitre / Abymes

Pointe-à-Pitre, Guadeloupe

Location

Related Publications (4)

• Fayad AI, Buamscha DG, Ciapponi A. Timing of kidney replacement therapy initiation for acute kidney injury. Cochrane Database Syst Rev. 2022 Nov 23;11(11):CD010612. doi: 10.1002/14651858.CD010612.pub3.

  PMID: 36416787 DERIVED

• Gaudry S, Hajage D, Martin-Lefevre L, Lebbah S, Louis G, Moschietto S, Titeca-Beauport D, Combe B, Pons B, de Prost N, Besset S, Combes A, Robine A, Beuzelin M, Badie J, Chevrel G, Bohe J, Coupez E, Chudeau N, Barbar S, Vinsonneau C, Forel JM, Thevenin D, Boulet E, Lakhal K, Aissaoui N, Grange S, Leone M, Lacave G, Nseir S, Poirson F, Mayaux J, Asehnoune K, Geri G, Klouche K, Thiery G, Argaud L, Rozec B, Cadoz C, Andreu P, Reignier J, Ricard JD, Quenot JP, Dreyfuss D. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial. Lancet. 2021 Apr 3;397(10281):1293-1300. doi: 10.1016/S0140-6736(21)00350-0.

  PMID: 33812488 DERIVED

• Meraz-Munoz AY, Bagshaw SM, Wald R. Timing of kidney replacement therapy initiation in acute kidney injury. Curr Opin Nephrol Hypertens. 2021 May 1;30(3):332-338. doi: 10.1097/MNH.0000000000000707.

  PMID: 33767061 DERIVED

• Gaudry S, Hajage D, Martin-Lefevre L, Louis G, Moschietto S, Titeca-Beauport D, La Combe B, Pons B, de Prost N, Besset S, Combes A, Robine A, Beuzelin M, Badie J, Chevrel G, Reignier J, Bohe J, Coupez E, Chudeau N, Barbar S, Vinsonneau C, Forel JM, Thevenin D, Boulet E, Lakhal K, Aissaoui N, Grange S, Leone M, Lacave G, Nseir S, Poirson F, Mayaux J, Asehnoune K, Geri G, Klouche K, Thiery G, Argaud L, Ricard JD, Quenot JP, Dreyfuss D. The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial. Trials. 2019 Dec 16;20(1):726. doi: 10.1186/s13063-019-3774-9.

  PMID: 31843007 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Didier DREYFUSS, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 11, 2018
• Study Start: May 7, 2018
• Primary Completion: October 11, 2019
• Study Completion: March 15, 2020
• Last Updated: June 16, 2021

Record last verified: 2021-06

Locations

GU (1); FR (40)