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

Primary Purpose

Acute Kidney Injury

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Fast ultrafiltration challenge

Slow ultrafiltration challenge

About this trial

This is an interventional diagnostic trial for Acute Kidney Injury focused on measuring acute kidney injury, renal replacement therapy, hemodynamics, preload dependence, net ultrafiltration

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Fast to Slow Group

Slow to Fast Group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

UF challenge diagnostic performance to identify preload dependence risk, evaluated by the area under the curve of the receiver-operating characteristic curve (ROC) of the relative cardiac output variation

The discriminatory performance of the relative variation in cardiac output (in %) between baseline and after the UF challenge will be quantified using the ROC, using the result of the postural change maneuver (negative or positive) performed after the UF challenge as the reference binary classifier. A 95% confidence interval of the ROC will be computed, as well as its statistical significance, as compared to a random guess, using the Delong method.

Secondary Outcome Measures

Respective diagnostic performances of slow and fast UF challenges to identify preload dependence risk, evaluated by their respective ROC of the relative cardiac output variation.

The discriminatory performance of the relative variation in cardiac output (in %) between baseline and after each UF challenge (slow and fast) will be quantified using the ROC, using the result of the postural change maneuver (negative or positive) performed after the UF challenge as the reference binary classifier. A 95% confidence interval of the ROC will be computed, as well as its statistical significance, as compared to a random guess, using the Delong method.

Optimal threshold value of the relative cardiac output variation (in %) following a UF challenge

using the ROC of the relative cardiac output variation induced by UF challenges, an optimal cutoff value will be determined, using the Youden method. This optimal threshold will allow the associated parameters describing its diagnostic performance: sensitivity, specificity, positive and negative predictive values, likelihood ratios.

UF challenge diagnostic performance to identify pre-existing preload dependence, evaluated by the ROC of the relative cardiac output variation.

The discriminatory performance of the relative variation in cardiac output (in %) between baseline and after the UF challenge will be quantified using the ROC, using the result of the postural change maneuver (negative or positive) performed before the UF challenge as the reference binary classifier. A 95% confidence interval of the ROC will be computed, as well as its statistical significance, as compared to a random guess, using the Delong method.

Comparison of slow and fast UF challenge diagnostic performance, using their respective ROC of relative cardiac output variation.

Statistical comparison of slow and fast UF challenges ROCs will be performed using the Delong methods

Impact of UF challenges on hemodynamics: central venous pressure (mmHg), heart rate (bpm), mean and pulse arterial pressures (mmHg), extravascular lung water (ml/kg), vascular permeability, and global end diastolic volume (ml/kg).

Each parameter will be evaluated individually, and its absolute and relative variations from baseline reported. The respective effect of slow and fast UF challenges will also be compared, using mixed effects models, accounting for the repetition of measurements in enrolled patients.

Association of UF challenges with hemodynamic instability, quantified by the elapsed time between the UF challenge and the occurrence of first hemodynamic instability episode, censored at 8 hours.

Following UF challenges, and over the 8 following hours, we will record all following hemodynamic events: mottles appearance or extension, de novo tachycardia > 120 bpm, de novo arterial hypotension (defined as a mean arterial pressure < 65 mmHg requiring immediate clinical intervention), or de novo cardiac output drop (defined as a decrease > 15% or below 2.2 L/min/m2). The time to event will be analyzed using a Cox mixed effects regression model, adjusted for patient severity of illness.

Full Information

NCT ID

NCT05214729

First Posted

January 17, 2022

Last Updated

August 17, 2022

Sponsor

Hospices Civils de Lyon

1. Study Identification

Unique Protocol Identification Number

NCT05214729

Brief Title

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

Acronym

UF CHALLENGE

Official Title

Diagnostic Performance of a Net Ultrafiltration Challenge to Predict Preload Dependence in Critically Ill Patients Under Continuous Renal Replacement Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Recruiting

Study Start Date

July 14, 2022 (Actual)

Primary Completion Date

January 2024 (Anticipated)

Study Completion Date

January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Kidney Injury

Keywords

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

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Fast to Slow Group

Arm Type

Experimental

Arm Description

Arm Title

Slow to Fast Group

Arm Type

Experimental

Arm Description

Intervention Type

Diagnostic Test

Intervention Name(s)

Fast ultrafiltration challenge

Intervention Description

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.

Intervention Type

Diagnostic Test

Intervention Name(s)

Slow ultrafiltration challenge

Intervention Description

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.

Primary Outcome Measure Information:

Title

Description

Time Frame

The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges. The postural maneuver is performed immediately after the end of UF challenges.

Secondary Outcome Measure Information:

Title

Respective diagnostic performances of slow and fast UF challenges to identify preload dependence risk, evaluated by their respective ROC of the relative cardiac output variation.

Description

Time Frame

The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges. The postural maneuver is performed immediately after the end of UF challenges.

Title

Optimal threshold value of the relative cardiac output variation (in %) following a UF challenge

Description

Time Frame

The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges.

Title

UF challenge diagnostic performance to identify pre-existing preload dependence, evaluated by the ROC of the relative cardiac output variation.

Description

The discriminatory performance of the relative variation in cardiac output (in %) between baseline and after the UF challenge will be quantified using the ROC, using the result of the postural change maneuver (negative or positive) performed before the UF challenge as the reference binary classifier. A 95% confidence interval of the ROC will be computed, as well as its statistical significance, as compared to a random guess, using the Delong method.

Time Frame

The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges. The postural maneuver is performed immediately before UF challenges.

Title

Comparison of slow and fast UF challenge diagnostic performance, using their respective ROC of relative cardiac output variation.

Description

Statistical comparison of slow and fast UF challenges ROCs will be performed using the Delong methods

Time Frame

The relative variation in cardiac output induced by UF challenges is quantified immediately at the end of UF challenges.

Title

Description

Time Frame

The variation in hemodynamic parameters induced by UF challenges is quantified immediately at the end of UF challenges.

Title

Association of UF challenges with hemodynamic instability, quantified by the elapsed time between the UF challenge and the occurrence of first hemodynamic instability episode, censored at 8 hours.

Description

Time Frame

Censor time at 8 hours after the end of the UF challenge. This evaluation and time frame is applied twice, after each UF challenge in all enrolled patients.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Laurent BITKER, MD

Phone

4 26 10 94 03

Ext

+33

laurent.bitker@chu-lyon.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Jean Christophe RICHARD, Pr

Phone

4 26 10 94 03

Ext

+33

j-christophe.richard@chu-lyon.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laurent BITKER, MD

Organizational Affiliation

Hospices Civils de Lyon

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Lyon

ZIP/Postal Code

69004

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Laurent BITKER, MD

Phone

4 26 10 94 03

Ext

+33

laurent.bitker@chu-lyon.fr

12. IPD Sharing Statement

Learn more about this trial

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

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