Hemodynamic Effects of Variations in Net Ultrafiltration Rate During Continuous Renal Replacement Therapy.

Hemodynamic Instability Clinical Trial

— NEPTUNE  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06071026
• Other study ID #: NIMAO/2022-2/SDB-01
• Status: Recruiting
• Phase: N/A
• Start date: October 6, 2023
• Est. completion date: December 21, 2025

Study information

• Verified date: October 2023
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: Saber D. BARBAR, MD, PhD
• Phone: 0033 4 66 68 33 20
• Email: saber.barbar[@]chu-nimes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 39
• Est. completion date: December 21, 2025
• Est. primary completion date: December 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fluid Overload
• Hemodynamic Instability

Intervention

Device:
• Net Ultra Filtration Rate
The net ultra filtration rate is modified every 6 hours accordingly to randomisation

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Nîmes	Nimes

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of HIRRT	Occurrence of Hemodynamic Instability related to Renal Replacement Therapy	6 hours
Secondary	Number of HIRRT	Number of HIRRT episodes in 6-hour sessions, i.e. number of hypotensive episodes during the 6-hour UFN cycle with mean arterial pressure < 65 mmHg [n]	6 hours
Secondary	Water depletion	Total volume of water depleted during 6-hour session [ml/kg/6h]	6 hours
Secondary	Fluid intake	The volume of all fluid intake (resuscitative fluids, transfusions of blood derivatives) during the 6-hour session [ml/kg/6h].	6 hours
Secondary	Time before HIRRT in each session	Time in hours between start of session and onset of hemodynamic instability (h)	6 hours
Secondary	Time between start of RRT and HIRRT	Time in hours between start of RRT and onset of hemodynamic instability (h)	28 days
Secondary	Atrial fibrillation	Proportion of sessions with onset of atrial fibrillation (%)	28 days
Secondary	Variation in norepinephrine	- variation between h0 and h6 in norepinephrine dosage [µg/kg/min].	6 hours
Secondary	Variations in central venous pressure	Variations between h0 and h6 in central venous pressure (CVP) [mmHg].	6 hours
Secondary	Variations in heart rate	Variations between h0 and h6 in heart rate [bpm].	6 hours
Secondary	Variations in arterial pressure	Variations between h0 and h6 in systolic, diastolic and mean arterial pressure (MAP) [mmHg].	6 hours
Secondary	Slope of arterial pressure	Slope of variation in systolic, diastolic and mean arterial pressure between h0 and h6 obtained with repeated hourly measurements	6 hours
Secondary	Frequency of episodes of arterial hypertension	Frequency of episodes between h0 and h6 of arterial hypertension defined by a systolic blood pressure greater than 180 mmHg [n].	6 hours
Secondary	Variations in arterial lactate levels	Variations between h0 and h6 in arterial lactate levels [mmol/l].	6 hours
Secondary	Variations in central venous oxygen saturation (SvcO2)	Variations between h0 and h6 in central venous oxygen saturation (SvcO2) measured in the superior vena cava [%].	6 hours
Secondary	Variations in hematocrit	Variations between h0 and h6 in hematocrit [%].	6 hours
Secondary	Variations in albuminemia	Variations between h0 and h6 in albuminemia [g/L].	6 hours
Secondary	Variations in natremia	Variations in natremia [mmol/L] between h0 and h6	6 hours
Secondary	Frequency of mottling	Frequency of clinical signs/symptoms potentially associated with per-dialytic hypotension during the session: mottling. [n]	6 hours