Clinical trial NCT06071026: Hemodynamic Effects of Variations in Net Ultrafiltration Rate During Continuous Renal Replacement Therapy.
Official title: Evaluation of the Hemodynamic Effect of Variations in Net Ultrafiltration Rate During Continuous Renal Replacement Therapy Sessions for Acute Renal Failure in Intensive Care Patients. Multiple N-of-1 Randomised Bi-centric Controlled Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fluid Overload
Hemodynamic Instability
Keywords: fluid overload
renal replacement therapy
hemodynamic instability
acute kidney injury
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2023-10-06
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Multiple N of one trial
Primary purpose: PREVENTION

Brief summary: Net ultra filtration (NUF) is one of the most important parameters during renal replacement therapy (RRT) whose role is to control fluid balance by water removal.

To our knowledge, there are no prospective studies or guidelines about the setting of this parameter.

In the NEPTUNE study, we aim to compare the hemodynamic effect of three NUF rates during RRT: 1 ml/kg/h, 2 ml/kg/h and 3 ml/kg/h.

The research hypothesis is that one of the three flow rates evaluated induces the fewest hemodynamic instabilities related to RRT, while guaranteeing the best possible fluid balance.

Detailed description: Renal renal replacement therapy (RRT) for severe acute kidney injury is one of the most widely used life-support techniques in intensive care. One of its main functions is to maintain the water balance in oligo-anuric patients by means of net ultrafiltration (NUF), defined as the volume of water removed from the patient by the RRT per unit time and indexed to the patient's weight.

Surprisingly, the setting of this parameter, which is one of the most important, there are no guidelines. If net ultrafiltration is too low, it may prolong RRT dependency and length of stay in the ICU, with all the associated care-related complications, and increase mortality. If net ultrafiltration is too high, it may transiently induce hypovolemia, leading to hemodynamic instability related to renal replacement therapy (HIRRT).

A recent survey of French practices shows that the average NUF flow rate used in intensive care units in France is 119 ± 77 ml/h, and the median flow rate is 100 ml/h \[min-max 20-300\]; in this study, NUF was not indexed by weight, but for a patient with an average weight of 75 kg, corresponding to an average NUF of 1.6 ± 1 ml/kg/h.

In the NEPTUNE study, the investigators aim to compare the hemodynamic effect of three net ultrafiltration rates during RRT: 1 ml/kg/h, 2 ml/kg/h and 3 ml/kg/h. These three flow rates are within the range of those usually used in clinical practice.The research hypothesis is that one of the three flow rates evaluated induces the fewest hemodynamic instabilities related to RRT, while guaranteeing the best possible fluid balance.

Eligibility criteria: Inclusion Criteria:

* Patients hospitalised in the intensive care unit of one of the two participating centres
* Patients with Kidney Disease: Improving Global Outcomes 3 (KDIGO3) acute kidney injury (AKI) requiring a continuous RRT during their stay in the intensive care unit, regardless of the aetiology of the AKI
* Need to prescribe water loss by net ultrafiltration (NUF), defined by at least one of the following sub-criteria:

  1. weight gain ≥ 1 kg relative to entry weight
  2. oligo-anuria ≥ 24 hours
  3. clinical impact of fluid overload as judged by the clinician: acute lung oedema clinical or at CT-scan, difficulty of weaning from mechanical ventilation.
* Hemodynamic stability in the 2 hours preceding the start of NUF, defined by all of the following sub-criteria:

  1. absence of vasopressors (noradrenaline) or stability or reduction in their dosage
  2. no need for resuscitative fluids as judged by the clinician
* Patient or his/her trusted support person/legal representative/family member having given free and informed consent, and having signed the consent form or patient included in an emergency situation.
* Patient affiliated to or benefiting from a health insurance scheme.

Exclusion Criteria:

* Patient moribund, with life expectancy too low to benefit from treatment, or with decision to discontinue treatment
* Patient participating in an another interventional study
* Patient in exclusion period determined by another study
* Patient under court protection or guardianship
* Patient/trusted person/legal representative/family member for whom it is impossible to give informed information.
* Pregnant, parturient or breast-feeding patient.

Primary outcomes:
measure: Occurrence of HIRRT
timeFrame: 6 hours
Secondary outcomes:
measure: Number of HIRRT
timeFrame: 6 hours
measure: Water depletion
timeFrame: 6 hours
measure: Fluid intake
timeFrame: 6 hours
measure: Time before HIRRT in each session
timeFrame: 6 hours
measure: Time between start of RRT and HIRRT
timeFrame: 28 days
measure: Atrial fibrillation
timeFrame: 28 days
measure: Variation in norepinephrine
timeFrame: 6 hours
measure: Variations in central venous pressure
timeFrame: 6 hours
measure: Variations in heart rate
timeFrame: 6 hours
measure: Variations in arterial pressure
timeFrame: 6 hours
measure: Slope of arterial pressure
timeFrame: 6 hours
measure: Frequency of episodes of arterial hypertension
timeFrame: 6 hours
measure: Variations in arterial lactate levels
timeFrame: 6 hours
measure: Variations in central venous oxygen saturation (SvcO2)
timeFrame: 6 hours
measure: Variations in hematocrit
timeFrame: 6 hours
measure: Variations in albuminemia
timeFrame: 6 hours
measure: Variations in natremia
timeFrame: 6 hours
measure: Frequency of mottling
timeFrame: 6 hours
Other outcomes:
Locations:
city: Nimes
country: France
facility: Centre Hospitalier Universitaire de Nîmes
Study officials:
affiliation: Centre Hospitalier Universitaire de Nīmes
name: Saber D. BARBAR, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11.
citation: Murugan R, Balakumar V, Kerti SJ, Priyanka P, Chang CH, Clermont G, Bellomo R, Palevsky PM, Kellum JA. Net ultrafiltration intensity and mortality in critically ill patients with fluid overload. Crit Care. 2018 Sep 24;22(1):223. doi: 10.1186/s13054-018-2163-1.
citation: Sharma S, Waikar SS. Intradialytic hypotension in acute kidney injury requiring renal replacement therapy. Semin Dial. 2017 Nov;30(6):553-558. doi: 10.1111/sdi.12630. Epub 2017 Jun 30.
citation: Murugan R, Kerti SJ, Chang CH, Gallagher M, Neto AS, Clermont G, Ronco C, Palevsky PM, Kellum JA, Bellomo R. Association between Net Ultrafiltration Rate and Renal Recovery among Critically Ill Adults with Acute Kidney Injury Receiving Continuous Renal Replacement Therapy: An Observational Cohort Study. Blood Purif. 2022;51(5):397-409. doi: 10.1159/000517281. Epub 2021 Jul 21.