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

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

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

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury; Fluid Overload
• Intervention / Treatment: Procedure: Fluid balance negativation; Procedure: Body weight Stabilization

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthias JACQUET LAGREZE, MD PhD; Phone Number: +33 04 72 35 79 41; Email: Matthias.jacquet-lagreze@chu-lyon.fr
• Study Contact Backup: Name: Julia CANTERINI, project manager; Phone Number: +33 04 27 85 66 28; Email: Julia.canterini@chu-lyon.fr

Study Locations

• France
  • Ajaccio, France, 20090
    • Not yet recruiting
    • Centre Hospitalier d'Ajaccio
    • Contact: Marie Geniez, Md; Phone Number: +33 04 95 29 91 25; Email: marie.geniez@ch-ajaccio.fr
    • Principal Investigator: Marie Geniez, MD
  • Amiens, France, 80480
    • Not yet recruiting
    • CHU Amiens-Picardie
    • Contact: Osama ABOU ARAB, Pr; Phone Number: +33 03 22 08 78 36; Email: abouarab.osama@chu-amiens.fr
    • Principal Investigator: Osama ABOU ARAB, Pr
  • Bron, France, 69500
    • Recruiting
    • Service d'Anesthesie-Réanimation, Hôpital Louis Pradel, Hospices Civils de Lyon
    • Contact: Matthias JACQUET LAGREZE, MD; Phone Number: +33 04 72 35 79 41; Email: Matthias.jacquet-lagreze@chu-lyon.fr
  • Caen, France, 14033
    • Not yet recruiting
    • CHU Caen Normandie
    • Contact: Sébastien DERVILLE, Dr; Phone Number: +33 02 31 06 47 36; Email: derville-s@chu-caen.fr
    • Principal Investigator: Sébastien DERVILLE, Dr
  • Dijon, France, 21000
    • Recruiting
    • Service de Réanimation, CHU de Dijon
    • Contact: Pierre-Grégoire GUINOT, MD; Phone Number: +33 03 80 29 56 03; Email: pierregregoire.guinot@chu-dijon.fr
  • Le Plessis-Robinson, France, 92350
    • Not yet recruiting
    • GHP Saint Joseph Marie Lannelongue
    • Contact: Thibaut GENTY, Dr; Phone Number: +33 01 40 94 22 60; Email: t.genty@ghpsj.fr
    • Principal Investigator: Thibaut GENTY, Dr
  • Lille, France, 59037
    • Not yet recruiting
    • CHU Lille - Hôpital Roger Salengro
    • Contact: Laurent ROBRIQUET, Dr; Phone Number: +33 03 20 44 40 84; Email: Laurent.ROBRIQUET@chu-lille.fr
    • Principal Investigator: Laurent ROBRIQUET, Dr
  • Lyon, France, 69004
    • Recruiting
    • Hôpital de la Croix Rousse
    • Principal Investigator: Marie-Charlotte Delignette, MD
    • Contact: Marie-Charlotte Delignette, MD; Phone Number: 33 04 72 11 89 47; Email: marie-charlotte.delignette@chu-lyon.fr
  • Lyon, France, 69004
    • Not yet recruiting
    • Hôpital de la Croix Rousse
    • Contact: Laurent Bitker, MD; Phone Number: +33 04 26 10 92 69; Email: laurent.bitker@chu-lyon.fr
    • Principal Investigator: Laurent Bitker, MD
  • Lyon, France, 69437
    • Not yet recruiting
    • Hôpital Edouard Herriot
    • Contact: Martin COUR, MD; Phone Number: 33 04 72 11 28 62; Email: martin.cour@chu-lyon.fr
    • Principal Investigator: Martin COUR, MD
  • Lyon, France, 69003
    • Recruiting
    • Hôpital Edouard Herriot, Groupement Hospitalier Centre
    • Contact: Frank Bidar, MD; Phone Number: +33 0472116942; Email: frank.bidar@chu-lyon.fr
    • Principal Investigator: Frank Bidar, MD
  • Lyon, France, 69009
    • Recruiting
    • Service de Réanimation, Clinique de la Sauvegarde
    • Contact: Guillaume Boulay, MD; Phone Number: +33 04 78 64 06 50; Email: guillaumeboulay85@gmail.com
    • Principal Investigator: Guillaume Boulay, MD
  • Paris, France, 75015
    • Recruiting
    • Département d'anesthésie réanimation Hôpital Européen Georges Pompidou
    • Contact: Nicolas POLGE, MD; Phone Number: +33 01 56 09 34 25; Email: nicolas.polge@aphp.fr
  • Vandœuvre-lès-Nancy, France, 54511
    • Not yet recruiting
    • Hôpitaux de Bradois - CHRU Nancy
    • Contact: Philippe GUERCY, Professor; Phone Number: +33 03 83 15 79 95; Email: P.GUERCI@chru-nancy.fr
    • Principal Investigator: Philippe GUERCY, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Acute kidney injury treated by continuous renal replacement therapy in ICU less than 7 days,
2. At least 1 organ failure during ICU in addition to AKI (mechanical ventilation or oxygen therapy or vascular filling > 1000ml or vasopressor exposure > 12 hours),
3. Weight loss of less than 3% since starting a net UF or Cumulative UF net less than 2000ml before inclusion,
4. Norepinephrine < 0,5 µg/kg/min,

5. Absence of hypoperfusion signs defined by the presence of at least 2 out of 4 criteria:

   • TRC > 3s at the finger
   • Marbrure score > 2
   • Lactate > 2 mmol/L
   • ScVO2< 60%,

6. Fluid overload defined as follows :

   • fluid overload > 5% of base weight (based on cumulative fluid balance or a weight gain) and/or
   • Obvious oedema of the lumbar region or flanks (oedema > 1cm bucket depth).

Exclusion Criteria:

1. Chronic renal failure hemodialyzed before admission to the ICU,
2. Mechanical circulatory support (ECMO, LVAD),
3. Pregnant, child -bearing age or lactating women,
4. Stroke based on the combination of central neurological symptoms (aphasia, hemiplegia, hemiparesis) associated with compatible brain imaging, less than 30 days,
5. Intestinal ischemia less than 7 days documented non-operated,
6. Interventional study participation or exclusion period on going,that may interfere with the present study
7. Guardianship, curatorship or safeguard of justice,
8. Absence of signature of free and informed consent by the patient and/or relative,
9. Patients not affiliated to a social security scheme or beneficiaries of a similar scheme

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Corrective strategy; 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; 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.
Other: Stabilizing strategy; 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; 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 >3% after 24h), the UF net can be increased to 1,5 ml/kg/h, as long as high intakes require UFnette at 1.5mL/kg/h to stabilize water balance, with daily reassessment. 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.

What is the study measuring?

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
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
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
SOFA score evolution	SOFA score : Sepsis-related Organ Failure Assessment, min : 0 max : 24 (worse)	From Day 0 up to Day 5
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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): January 15, 2028

Study Registration Dates

• First Submitted: April 5, 2023
• First Submitted That Met QC Criteria: April 17, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Fluid overload; Fluid balance; Ultrafiltration; Deresuscitation; Tissue perfusion; Renal Replacement Therapy (RRT)
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Acute Kidney Injury; Edema
• Other Study ID Numbers: 69HCL22_1095

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No