Trial Outcomes & Findings for A Net Ultrafiltration Challenge to Predict Preload-dependence (UF CHALLENGE) (NCT NCT05214729)

NCT ID: NCT05214729

Last Updated: 2026-02-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

20 participants

Primary outcome timeframe

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

Results posted on

2026-02-13

Participant Flow

64 patients were screened between june 2022 and december 2024

20 patients were randomized. Of the 44 not randomized, 44 met inclusion criteria and met exclusion criteria.

Participant milestones

Participant milestones
Measure
Slow to Fast Group
The Slow to Fast Group corresponds to enrolled patients randomized, following the sequential crossover design, to first perform the slow ultrafiltration challenge immediately after inclusion, followed by the fast ultrafiltration challenge after a washout period of 24 hours. 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. 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.
Fast to Slow Group
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. 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. 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.
First Challenge (15 or 30 Minutes)
STARTED
10
10
First Challenge (15 or 30 Minutes)
Received the Intervention
10
10
First Challenge (15 or 30 Minutes)
COMPLETED
10
10
First Challenge (15 or 30 Minutes)
NOT COMPLETED
0
0
Wash-out Period (24 to 48h)
STARTED
10
10
Wash-out Period (24 to 48h)
COMPLETED
9
7
Wash-out Period (24 to 48h)
NOT COMPLETED
1
3
Second Challenge (15 or 30 Minutes)
STARTED
9
7
Second Challenge (15 or 30 Minutes)
Received the Intervention
9
7
Second Challenge (15 or 30 Minutes)
COMPLETED
9
7
Second Challenge (15 or 30 Minutes)
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Slow to Fast Group
The Slow to Fast Group corresponds to enrolled patients randomized, following the sequential crossover design, to first perform the slow ultrafiltration challenge immediately after inclusion, followed by the fast ultrafiltration challenge after a washout period of 24 hours. 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. 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.
Fast to Slow Group
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. 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. 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.
Wash-out Period (24 to 48h)
Cardiac index > 4 L/min/m2
0
2
Wash-out Period (24 to 48h)
Preload dependent prior to 2nd challenge
0
1
Wash-out Period (24 to 48h)
Expected death in the following 24h
1
0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Fast to Slow Group
n=10 Participants
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. 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. 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.
Slow to Fast Group
n=10 Participants
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. 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. 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.
Total
n=20 Participants
Total of all reporting groups
Age, Continuous
64 years
n=10 Participants
62 years
n=10 Participants
62 years
n=20 Participants
Sex: Female, Male
Female
1 Participants
n=10 Participants
2 Participants
n=10 Participants
3 Participants
n=20 Participants
Sex: Female, Male
Male
9 Participants
n=10 Participants
8 Participants
n=10 Participants
17 Participants
n=20 Participants
Race and Ethnicity Not Collected
0 Participants
Race and Ethnicity were not collected from any participant.
Region of Enrollment
France
10 participants
n=10 Participants
10 participants
n=10 Participants
20 participants
n=20 Participants
Sepsis-related Organ Failure Assessment (SOFA)
12 Units on a scale
n=10 Participants
12 Units on a scale
n=10 Participants
12 Units on a scale
n=20 Participants
Norepinephrine dose (tartrate formula)
0.22 µg/kg/min
n=10 Participants
0.23 µg/kg/min
n=10 Participants
0.22 µg/kg/min
n=20 Participants

PRIMARY outcome

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

Population: All enrolled patients underwent two UF NET challenges, one fast and one slow, consisting in the removal of 250 ml of ultrafiltrate in randomized order and in a cross-over design (with a 24h wash-out period between challenged). 4 patients did not perform the second challenge due to the presence of predefined exit criteria during the wash-out period, as defined by the allocations sequence.

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.

Outcome measures

Outcome measures
Measure
All UF NET Challenges
n=36 UF NET challenges
All completed UF NET challenges (irrespective of their duration, i.e. fast or slow) are pooled and analyzed together for the primary outcome.
Slow UF NET Challenge
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.
Slow UF NET Challenge
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.
Diagnostic Performance of the Net Ultrafiltration (UF NET) Challenge to Detect de Novo Preload Dependence
0.74 Proportion probability (0 to 1)
Interval 0.58 to 0.88

SECONDARY outcome

Timeframe: Between baseline and end of the UF NET challenge

Population: All enrolled patients underwent two UF NET challenges, one fast and one slow, consisting in the removal of 250 ml of ultrafiltrate in randomized order and in a cross-over design (with a 24h wash-out period between challenged). 4 patients did not perform the second challenge (1 fast and 3 slow) due to the presence of predefined exit criteria during the wash-out period.

The respective diagnostic performance of fast and slow challenges 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 fast and slow challenges, 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.

Outcome measures

Outcome measures
Measure
All UF NET Challenges
n=19 UF NET Challenges
All completed UF NET challenges (irrespective of their duration, i.e. fast or slow) are pooled and analyzed together for the primary outcome.
Slow UF NET Challenge
n=17 UF NET Challenges
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.
Slow UF NET Challenge
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.
Respective Diagnostic Performance of the Fast and Slow Net Ultrafiltration (UF NET) Challenge to Detect de Novo Preload Dependence
0.71 Proportion probability (0 to 1)
Interval 0.49 to 0.91
0.69 Proportion probability (0 to 1)
Interval 0.36 to 1.0

SECONDARY outcome

Timeframe: At the end of the UF NET challenge

Population: Five challenges (4 fast, 1 slow, all related to the first visit) were a posteriori identified as being preload-dependent prior to challenge start, leaving 31 challenges (in 17 patients) out of a total of 36 challenges (in 20 patients). This analysis was a priori planned to be performed on all UF NET challenges (irrespective of their duration, slow or fast), and each study groups (slow and fast, respectively).

The rate (in %) of UF NET challenges after which a preload-dependence status was identified using the reference diagnostic method, consisting of a postural maneuver (passive leg raising or Trendelenburg maneuver) during which the relative variation in pulse-contour continuous cardiac index was assessed over 1 minute. The test was positive if the relative variation in pulse-contour continuous cardiac index increased by more than 10% during the maneuver, and negative otherwise.

Outcome measures

Outcome measures
Measure
All UF NET Challenges
n=31 UF NET challenges
All completed UF NET challenges (irrespective of their duration, i.e. fast or slow) are pooled and analyzed together for the primary outcome.
Slow UF NET Challenge
n=15 UF NET challenges
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.
Slow UF NET Challenge
n=16 UF NET challenges
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.
Preload Dependence Prevalence After a UF NET Challenge
9 UF NET challenges
6 UF NET challenges
3 UF NET challenges

Adverse Events

Fast UF NET Challenge

Serious events: 11 serious events
Other events: 0 other events
Deaths: 0 deaths

Slow UF NET Challenge

Serious events: 13 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Fast UF NET Challenge
n=19 participants at risk
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.
Slow UF NET Challenge
n=17 participants at risk
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.
Cardiac disorders
Norepinephrine increase during the UF NET challenge
0.00%
0/19 • From enrollment until end of follow-up (8h after the end of the second challenge, that is within a maximum time range of 56 hours avec enrollment)
The overall mortality rate is reported to the number of participants at risk (N=20). Other severe adverse events are reported to the number of challenges at risk (N=36).
5.9%
1/17 • From enrollment until end of follow-up (8h after the end of the second challenge, that is within a maximum time range of 56 hours avec enrollment)
The overall mortality rate is reported to the number of participants at risk (N=20). Other severe adverse events are reported to the number of challenges at risk (N=36).
Nervous system disorders
Change in sedation dose
5.3%
1/19 • From enrollment until end of follow-up (8h after the end of the second challenge, that is within a maximum time range of 56 hours avec enrollment)
The overall mortality rate is reported to the number of participants at risk (N=20). Other severe adverse events are reported to the number of challenges at risk (N=36).
0.00%
0/17 • From enrollment until end of follow-up (8h after the end of the second challenge, that is within a maximum time range of 56 hours avec enrollment)
The overall mortality rate is reported to the number of participants at risk (N=20). Other severe adverse events are reported to the number of challenges at risk (N=36).
Cardiac disorders
Hemodynamic instability episode during the 8h follow-up period after the challenge
52.6%
10/19 • From enrollment until end of follow-up (8h after the end of the second challenge, that is within a maximum time range of 56 hours avec enrollment)
The overall mortality rate is reported to the number of participants at risk (N=20). Other severe adverse events are reported to the number of challenges at risk (N=36).
70.6%
12/17 • From enrollment until end of follow-up (8h after the end of the second challenge, that is within a maximum time range of 56 hours avec enrollment)
The overall mortality rate is reported to the number of participants at risk (N=20). Other severe adverse events are reported to the number of challenges at risk (N=36).

Other adverse events

Adverse event data not reported

Additional Information

Dr Laurent BITKER

Hospices Civils de Lyon

Phone: 4 26 10 92 69

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place