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

Official title

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

Overview

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

Interventions

• 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/
• 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.

Primary outcome measures

• Number of organ replacement free-days [Time frame: Day 30]

Secondary outcome measures (11)

• Mortality decrease [Time frame: 30 days]
• Number of renal replacement therapy-free days increase [Time frame: Day 30]
• Number of ventilator-free day increase [Time frame: Day 30]
• Number of vasopressor-free day increase [Time frame: Day 30]
• Duration of intensive care unit stay [Time frame: Up to Day 30]
• SOFA score evolution [Time frame: From Day 0 up to Day 5]
• Incidence of arrhythmias and cardiac conduction disorders in both group [Time frame: From Day 0 up to Day 5]
• Incidence of intestinal ischemia in both group [Time frame: From Day 0 to Day 30]
• Incidence of strokes [Time frame: From Day 0 to Day 30]
• Incidence of delirium [Time frame: Between Day 0 and Day 5]
• Renal recovery assessment [Time frame: Day 30]

Eligibility criteria

Inclusion criteria

• Acute kidney injury treated by continuous renal replacement therapy in ICU less than 7 days,
• 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),
• Weight loss of less than 3% since starting a net UF or Cumulative UF net less than 2000ml before inclusion,
• Norepinephrine < 0,5 µg/kg/min,
• 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%,
• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Other

Study locations

France · 14 centers

• Centre Hospitalier d'Ajaccio — Ajaccio
• CHU Amiens-Picardie — Amiens
• Service d'Anesthesie-Réanimation, Hôpital Louis Pradel, Hospices Civils de Lyon — Bron
• CHU Caen Normandie — Caen
• Service de Réanimation, CHU de Dijon — Dijon
• GHP Saint Joseph Marie Lannelongue — Le Plessis-Robinson
• CHU Lille - Hôpital Roger Salengro — Lille
• Hôpital Edouard Herriot, Groupement Hospitalier Centre — Lyon
• … and 6 more centers

Identifiers

NCT: NCT05817539 · 69HCL22_1095

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗