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The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2)

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ClinicalTrials.gov Identifier: NCT03396757
Recruitment Status : Recruiting
First Posted : January 11, 2018
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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).

Condition or disease Intervention/treatment Phase
Renal Replacement Therapy for Acute Kidney Injury in ICU Procedure: Standard strategy Procedure: Delayed strategy Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 810 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Artificial Kidney Initiation in Kidney Injury 2 A Multi-Centre, Randomized, Controlled Trial
Actual Study Start Date : May 7, 2018
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Active Comparator: Standard strategy
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
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),

Experimental: Delayed strategy
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

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.





Primary Outcome Measures :
  1. number of RRT-free days [ Time Frame: Day 28 after randomization ]

    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).



Secondary Outcome Measures :
  1. Hydration status (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    weight

  2. Hydration status (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    clinical edema scale

  3. Hydration status (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    fluid balance

  4. Nutritional status (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    Amount of calories and protein administered

  5. Nutritional status (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    serum albumin, transthyretin and CRP (C Reactive Protein) concentration changes

  6. Number of hemorrhages (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    hemorrhages requiring red blood cell transfusion or surgical procedure

  7. Rate of thrombocytopenia (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    thrombocytopenia (< 100 000 platelets/mm3)

  8. Rate of thrombosis of a large venous axis (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    thrombosis of a large venous axis diagnosed by Doppler ultrasonography

  9. Rate of hypophosphatemia (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    hypophosphatemia (defined as a serum phosphate concentration<0.6 mmol/l)

  10. Rate of hyperkalemia (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    hyperkalemia (> 6.5 mmol/l)

  11. Rate of hypernatremia (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    Hypernatremia (>150 mmol/l)

  12. Rate of cardiac rhythm disorders (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    ventricular tachycardia, ventricular fibrillation, torsade de pointe or new episode of atrial fibrillation requiring medical treatment or external electric counter shock

  13. Rate of pneumothorax (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  14. Rate of hemothorax (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  15. Rate of air embolism (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  16. Number of arterio-venous fistulae (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  17. Rate of pericarditis (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  18. Rate of unexpected cardiac arrest (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  19. Rate of hypothermia (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    Hypothermia (<34°C)

  20. Percentage of patients receiving RRT at least once in the " delayed" RRT strategy arm (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  21. Number of RRT sessions (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    Number of RRT sessions (until D28 after randomization) (analyzing alive or dead patients separately)

  22. Time between randomization and RRT initiation (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  23. Time to RRT weaning (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  24. Time to renal function recovery (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  25. Total cost of RRT-related consumables (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    catheters, solutions for RRT, membranes, and circuitry

  26. Number of dialysis catheter-free day (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  27. Rate of catheter-related bloodstream infection (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    both dialysis and non-dialysis catheters

  28. Barthel ADL (activity of daily living) index (randomization stage) [ Time Frame: Day 60 after randomization ]
    Barthel ADL index at D60 (an index of activities of daily living)

  29. Percentage of patients with a decisions to withhold or withdraw life support therapies (randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
  30. Duration of ICU stay (observational and randomization stage) [ Time Frame: Limited to 60 days after randomization ]
  31. Duration of hospital stay (observational and randomization stage) [ Time Frame: Limited to 60 days after randomization ]
  32. ICU mortality (observational and randomization stage) [ Time Frame: Limited to 60 days after randomization ]
  33. Day 28 mortality (observational and randomization stage) [ Time Frame: Day 28 after inclusion ]
  34. Day 60 mortality (observational and randomization stage) [ Time Frame: Day 60 after inclusion ]
  35. Hospital mortality (observational and randomization stage) [ Time Frame: Limited to 60 days after randomization ]
  36. Ventilator free-days (observational and randomization stage) [ Time Frame: Day 28 after inclusion ]
  37. RRT indications (observational and randomization stage) [ Time Frame: Day 28 after inclusion ]
    Reason(s) to start RRT during observational stage will be assessed

  38. RRT modalities (observational and randomization stage) [ Time Frame: Day 28 after inclusion ]
    CRRT (continuous renal replacement therapy) , IHD (Intermittent Hemodialysis), other

  39. Duration of RRT [ Time Frame: Until ICU discharge or day 28 after randomization ]
  40. Time to renal function recovery (observational and randomization stage) [ Time Frame: Until ICU discharge or day 28 after randomization ]
    Renal function recovery will be defined by spontaneous diuresis >1000 ml/24h without diuretic administration or >2000 ml/24h, in patients receiving diuretics.

  41. Time to spontaneous decrease in creatinine [ Time Frame: Until ICU discharge or day 28 after randomization ]
    Spontaneous decrease of serum creatinine for 2 consecutive days without need for RRT during the following 7 days



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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.

To be randomized (randomization stage), supplemental criteria must be fulfilled. These criteria can appear either immediately after inclusion in the observational stage, or during the follow-up of the patient in the observational stage, in the absence of any non-inclusion criteria (listed below) at the time of randomization:

  • 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

Exclusion Criteria:

  • 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)
  • Patients with inclusion criteria already present for more than 24 hours (to avoid delayed inclusions)
  • 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)
  • Previous inclusion in this study
  • Subject deprived of freedom, subject under a legal protective measure
  • Pregnant or breastfeeding woman

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03396757


Contacts
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Contact: Didier DREYFUSS, MD 0147606193 ext 33 didier.dreyfuss@aphp.fr
Contact: Stephane GAUDRY, MD 0147606855 ext 33 stephane.gaudry@aphp.fr

Locations
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France
CH Alès Terminated
Alès, France
CHU Amiens Recruiting
Amiens, France
Contact: Julien MAIZEL, MD         
CH Avignon Recruiting
Avignon, France
Contact: Sébastien MOSCHIETTO, MD         
Groupe Hospitalier Carnelle-Portes de l'Oise Site Beaumont / Oise Terminated
Beaumont-sur-Oise, France
Hopital Nord Franche Comté - Belfort Recruiting
Belfort, France
Contact: Julio BADIE, MD         
CHU Avicenne - APHP Recruiting
Bobigny, France
Contact: Yves COHEN, MD         
CHU Ambroise Paré - APHP Recruiting
Boulogne-Billancourt, France
Contact: Guillaume GERI, MD         
CH Bourg en Bresse / Fleyriat Recruiting
Bourg-en-Bresse, France
Contact: Rémi BRUYERE, MD         
CH Béthune Beuvry - Germont et Gauthier Recruiting
Béthune, France
Contact: Christophe VINSONNEAU, MD         
Gabriel Montpied - CHU Clermont Ferrand Recruiting
Clermont-Ferrand, France
Contact: Elizabeth COUPEZ, MD         
CHU Louis Mourier - APHP Recruiting
Colombes, France, 92700
Contact: Stéphane GAUDRY, MD    33 1 47606855    stephane.gaudry@aphp.fr   
CH Sud Francilien Recruiting
Corbeil-Essonnes, France
Contact: Guillaume CHEVREL, MD         
CHU Henri Mondor - APHP Recruiting
Créteil, France
Contact: Nicolas DE PROST, MD         
CH Dieppe Recruiting
Dieppe, France
Contact: Marion BEUZELIN, MD         
Hôpital François Mitterand - CHU Dijon Recruiting
Dijon, France
Contact: Jean-Pierre QUENOT, MD         
CHD Vendée Recruiting
La Roche Sur Yon, France, 85925
Contact: Laurent MARTIN LEFEBVRE, MD         
CH Le Mans Recruiting
Le Mans, France
Contact: Nicolas CHUDEAU, MD         
CH Dr Schaffner - Lens Recruiting
Lens, France
Contact: Didier THEVENIN, MD         
Hôpital Roger Salengro / CHRU Lille Recruiting
Lille, France
Contact: Saad NSEIR, MD         
Centre Hospitalier Bretagne sud - Lorient Recruiting
Lorient, France
Contact: Béatrice LACOMBE, MD         
GH Edouard Herriot - Lyon Recruiting
Lyon, France
Contact: ARGAUD Laurent, MD         
Hôpital Nord - Anesthésie Réa - APHM Recruiting
Marseille, France
Contact: Marc LEONE, MD         
Hôpital Nord - DRIS - APHM Recruiting
Marseille, France
Contact: Jean-Marie FOREL, MD         
La Timone - APHM Terminated
Marseille, France
Hopital de Mercy, CHR Metz-Thionville Recruiting
Metz, France
Contact: Guillaume LOUIS, MD         
Hôpital Lapeyronie - CHU Montpellier Recruiting
Montpellier, France
Contact: Kada KLOUCHE, MD         
Hôpital St Eloi - CHU Montpellier Terminated
Montpellier, France
Hotel Dieu - Anesthésie Réanimation - CHU Nantes Recruiting
Nantes, France
Contact: Karim ASHENOUNE, MD         
Hotel Dieu - Réanimation MIR - CHU Nantes Recruiting
Nantes, France
Contact: Jean REIGNIER, MD         
Hôpital Nord Laennec - CHU Nantes Recruiting
Nantes, France
Contact: Karim LAKHAL, MD         
CHU Nimes - Caremeau Recruiting
Nîmes, France
Contact: Saber BARBAR, MD         
Chu Hegp - Aphp Recruiting
Paris, France, 75015
Contact: Nadia AISSAOUI         
CHU Pitiè Salpêtrière - Pneumologie et réanimation médicale - APHP Recruiting
Paris, France, 75015
Contact: Julien MAYAUX, MD         
CHU Pitié-Salpêtrière - Réanimation médicale - APHP Recruiting
Paris, France
Contact: Alain COMBES, MD         
CHU Lyon Sud Recruiting
Pierre-Bénite, France
Contact: Julien BOHE, MD         
CHU Poitiers Recruiting
Poitiers, France
Contact: René ROBERT, MD         
CH René DUBOS Terminated
Pontoise, France
CHU Charles Nicolle Recruiting
Rouen, France
Contact: Steven GRANGE, MD         
Hopital Delafontaine Withdrawn
Saint-Denis, France
CHU Saint Etienne Recruiting
Saint-Étienne, France
Contact: Guillaume THIERY, MD         
CH André Mignot Recruiting
Versailles, France
Contact: Guillaume LACAVE, MD         
Guadeloupe
CHU pointe à Pitre / Abymes Recruiting
Pointe-à-Pitre, Guadeloupe
Contact: Bertrand PONS, MD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Didier DREYFUSS, MD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03396757     History of Changes
Other Study ID Numbers: K160916J
2017-A02382-51 ( Other Identifier: Sponsor code / IDRCB )
First Posted: January 11, 2018    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Acute Kidney Injury
Critical Care
Renal Replacement Therapy
Additional relevant MeSH terms:
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Acute Kidney Injury
Wounds and Injuries
Renal Insufficiency
Kidney Diseases
Urologic Diseases