A Net Ultrafiltration Challenge to Predict Preload-dependence (UF CHALLENGE)

NCT05214729 | Completed Results

• 2 other identifiers: 69HCL21_12502021-A02939-32
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Hemodynamic instability episodes are a frequent complication of renal replacement therapies in critically ill patients, and their incidence is associated with worse survival. Hypovolemia, identified by the existence of biventricular preload dependence, is responsible for one episode out of two, and may justify a decrease in or cessation of fluid removal by net ultrafiltration (UF). To date, preload dependence is most frequently identified by evaluating the effects on cardiac output of postural changes (passive leg raising), impact of cardio-pulmonary interactions in ventilated patients, or fluid challenge. However, none of these tests may help identify a patient whose cardiac output is at risk of becoming preload dependent, that is situated at the inflexion point of the Frank Starling curve. Our study aims to evaluate the effects on cardiac output (measured by a transpulmonary thermodilution technique) of 2 net ultrafiltration challenges, consisting fast removal of 250 ml of ultrafiltrate over 15 and 30 minutes respectively, and compare their diagnostic performance to the reference technique of preload dependence assessed by postural changes (passive leg raising) performed after the UF challenge. Enrolled participants will undergo both UF challenges, following a randomized crossover design, in which the order of UF challenge duration (15 or 30 minutes) is randomized, separated by a washout period of 24 hours.

Conditions

Acute Kidney Injury

Keywords

acute kidney injury; renal replacement therapy; hemodynamics; preload dependence; net ultrafiltration

Outcome Measures

Primary Outcomes (1)

• Diagnostic Performance of the Net Ultrafiltration (UF NET) Challenge to Detect de Novo Preload Dependence

  The diagnostic performance was assessed using the area under the receiver-operating curve (AUROC) of the relative variation in calibrated cardiac index, measured at baseline and at the end of the challenge, and compared to the reference standard consisting in the result of a postural maneuver (passive leg raising or Trendelenburg) evaluating preload dependence using pulse-contour continuous cardiac index variation (positive if \> 10% or negative if ≤ 10%) performed at the end of the challenge.

  Baseline and immediately at the end ot each UF NET challenge (approximately 15-30 minutes, 1 day apart)

Secondary Outcomes (2)

• Respective Diagnostic Performance of the Fast and Slow Net Ultrafiltration (UF NET) Challenge to Detect de Novo Preload Dependence

  Between baseline and end of the UF NET challenge

• Preload Dependence Prevalence After a UF NET Challenge

  At the end of the UF NET challenge

Study Arms (2)

Fast to Slow Group

EXPERIMENTAL

The Fast to Slow Group corresponds to enrolled patients randomized, following the sequential crossover design, to first perform the fast UF challenge immediately after inclusion, followed by the slow UF challenge after a washout period of 24 hours.

Diagnostic Test: Fast ultrafiltration challenge; Diagnostic Test: Slow ultrafiltration challenge

Slow to Fast Group

EXPERIMENTAL

The Slow to Fast Group corresponds to enrolled patients randomized, following the sequential crossover design, to first perform the slow UF challenge immediately after inclusion, followed by the fast UF challenge after a washout period of 24 hours.

Diagnostic Test: Fast ultrafiltration challenge; Diagnostic Test: Slow ultrafiltration challenge

Interventions

Fast ultrafiltration challenge DIAGNOSTIC_TEST

The fast ultrafiltration challenge will be performed once in all enrolled participants, in the order defined by randomization. The fast ultrafiltration challenge consists of the net removal of 250 ml of ultrafiltrate by setting net ultrafiltration rate to 1000 ml/h, applied for 15 minutes. The cardiac output will be measured before and after the UF challenge, by mean of the transpulmonary thermodilution technique, and its relative variation from baseline will be quantified to evaluate the impact of the UF challenge on cardiac preload. The UF challenge will be preceded and immediately followed by a postural change maneuver to assess the presence or absence of preload dependence. The postural change maneuver is positive in case of a +10% variation in continuous cardiac index over 1 minute, and is considered as the reference diagnostic test to which UF challenge diagnostic performance will be compared.

Fast to Slow Group; Slow to Fast Group

Slow ultrafiltration challenge DIAGNOSTIC_TEST

The slow ultrafiltration challenge will be performed once in all enrolled participants, in the order defined by randomization. The slow ultrafiltration challenge consists of the net removal of 250 ml of ultrafiltrate by setting net ultrafiltration rate to 500 ml/h, applied for 30 minutes. The cardiac output will be measured before and after the UF challenge, by mean of the transpulmonary thermodilution technique, and its relative variation from baseline will be quantified to evaluate the impact of the UF challenge on cardiac preload. The UF challenge will be preceded and immediately followed by a postural change maneuver to assess the presence or absence of preload dependence. The postural change maneuver is positive in case of a +10% variation in continuous cardiac index over 1 minute, and is considered as the reference diagnostic test to which UF challenge diagnostic performance will be compared.

Fast to Slow Group; Slow to Fast Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult patient, aged 18 year or older
• under mechanical ventilation and continuous general anesthesia, with a positive end-expiratory pressure of 5 cmH2O or more
• with stage 3 KDIGO acute kidney injury
• treated with continuous renal replacement therapy for less than 14 days
• ongoing continuous cardiac output monitoring
• with a predicted intensive care length of stay of 24 hours or more at time of screening

You may not qualify if:

• High arterial lactate concentration, \> 4.0 mmol/L at time of screening
• Calibrated cardiac index \< 2.0 L/min/m2 or \> 4.0 L/min/m2 at time of screening
• Positive postural change maneuver in the last 2 hours preceding screening
• Patient under extracorporeal membrane oxygenation
• Patient with active bleeding requiring emergent transfusion
• Patient under chronic maintenance dialysis or renal transplant recipient
• Acute ischemic or hemorrhagic stroke complicated with coma and requiring mechanical ventilation
• Fulminant hepatitis (acute liver injury, hepatic encephalopathy, icterus and a drop in prothrombin \< 50% in less that 15 days
• Impossible postural change maneuver
• Pregnant or lactating patient
• Imminent death
• Patient under legal protection measures as by French regulation
• Patient already enrolled in the present study
• Patient already participates in a study with protocolized net ultrafiltration, ongoing at time of screening

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Department of Intensive Care, Croix Rousse hospital, Hospices Civils de Lyon

Lyon, 69004, France

Location

Related Publications (1)

• Biscarrat C, Deniel G, Chivot M, Yonis H, Chauvelot L, Mezidi M, Richard JC, Bitker L. Diagnostic performance of a 250-ml net ultrafiltration challenge to identify risk of preload-dependence in critically ill patients undergoing continuous renal replacement therapy: a randomized, cross-over trial. Crit Care. 2025 Oct 21;29(1):446. doi: 10.1186/s13054-025-05674-3.

  PMID: 41121412 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

* Studied population: patients at high HIRRT risk, being under CRRT, mechanical ventilation and frequently receiving vasopressors, and all equipped with a CCI monitoring device. * 5 patients were a posteriori identified as being preload-dependent after inclusion. * Respective numbers of slow and fast challenges may have been insufficient to detect statistical differences when comparing challenge types * Trial design did not include a parallel arm in which a UFNET challenge was not performed

Results Point of Contact

• Title: Dr Laurent BITKER
• Organization: Hospices Civils de Lyon

laurent.bitker@chu-lyon.fr

4 26 10 92 69

Study Officials

• Laurent BITKER, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: January 31, 2022
• Study Start: July 14, 2022
• Primary Completion: January 2, 2025
• Study Completion: January 2, 2025
• Last Updated: February 13, 2026
• Results First Posted: February 13, 2026

Record last verified: 2026-01

Locations

FR (1)