General Critically Ill Patients With HypovolemiaNCT06495489
Arterial Pressure Derived Dynamic Parameters to Detect Preload Responsiveness in Mechanically Ventilated Patients Under Spontaneous Mode
An observational study of General Critically Ill Patients With Hypovolemia, run by CHU de Reims at 1 site in France.
Trial summary
The management of septic shock patients includes the infusion of fluids, however fluids may be deleterious if the patient does not respond by increasing cardiac output. By consequence, it is now recommended to predict the fluid response (fluid or preload responsiveness) before infusing them. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- General Critically Ill Patients With Hypovolemia
- What is being tested?
- Detection of preload responders by a PLR test
- Type of treatment
- Injection or infusion
- How many people
- 34 participants
- Where
- 1 siteFrance
- Study dates
- 29 Jan 2024to 27 Mar 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: * Patient over 18 years old. * Hospitalized in intensive care. * For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of: * Acute circulatory failure with mean arterial pressure < 65mmHg or < 30mmHg of its baseline value for hypertensive patients. * And/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia). * In mechanically ventilated patients under spontaneous mode. * Previously equipped with an arterial catheter. * Affiliated to a social security scheme.
Who may be able to join
- Patient over 18 years old.
- Hospitalized in intensive care.
- For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of:
- Acute circulatory failure with mean arterial pressure < 65mmHg or < 30mmHg of its baseline value for hypertensive patients.
- And/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia).
- In mechanically ventilated patients under spontaneous mode.
- Previously equipped with an arterial catheter.
- Affiliated to a social security scheme.
Who cannot join
- Patient with arrythmia (PPV is not applicable).
- Patient with intra-abdominal hypertension (PLR test is not valid).
- Patient with a contraindication/impossibility to the PLR maneuver (lower limb amputation, respiratory intolerance).
- Patient with poor echogenicity noted previously.
- Patient protected by law.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Performance of Changes of Pulse Pressure and of Pulse Pressure Variation to Detect Preload Responsiveness in Mechanically Ventilated Patients Under a Spontaneous Mode
The management of septic shock patients includes the infusion of fluids, however fluids may be deleterious if the patient does not respond by increasing cardiac output. By consequence, it is now recommended to predict the fluid response (fluid or preload responsiveness) before infusing them. In this protocol, the investigators will include critically ill patients mechanically ventilated patients under a spontaneous mode, for whom the physician in charge has decided to test preload responsiveness. The investigators will collect from the continuous monitoring of arterial pressure of the patient the Pulse Pressure (PP) which is the difference between systolic arterial pressure and diastolic arterial pressure and the Pulse Pressure Variation (PPV) automatically displayed by the monitor in addition to other clinical (hemodynamic, respiratory) parameters. After one minute of Passive Leg Raising manoeuvre (PLR) the investigators collect the same parameters and the investigators will compare the changes of these parameters in patients who are preload responsive to patients who are not. Preload responsiveness will be defined by echocardiographic parameters before and during PLR. More exactly, a surrogate of cardiac output measured by echocardiography wich is VTI of the sub-aorti flow; an increase of more than 12% defines apreload responsive patient.
Read the detailed description
*Objectives:
Primary : to assess the diagnostic performance of the decrease in Pulse Pressure Variation (PPV) during a Passive Leg Raising test (PLR) to predict preload responsiveness in mechanically ventilated patients under spontaneous mode hospitalized in intensive care.
Secondary:
- Evaluate the diagnostic performance of the increase in Pulse Pressure (PP) during a PLR test to predict preload responsiveness in this same population.
- Compare before/after PLR measurements other hemodynamic data (blood pressure, cardiac output, heart rate).
- Experimental scheme: it is a diagnostic and monocentric study.
- Population / patients:
Inclusion criteria:
- Patient over 18 years old.
- Hospitalized in intensive care.
- For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of:
- Acute circulatory failure with mean arterial pressure < 65mmHg or < 30mmHg of its baseline value for hypertensive patients.
- And/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia).
- In mechanically ventilated patients under spontaneous mode.
- Previously equipped with an arterial catheter.
- Affiliated to a social security scheme.
Non-inclusion criteria:
- Patient with arrythmia (PPV is not applicable).
- Patient with intra-abdominal hypertension (PLR test is not valid).
- Patient with a contraindication/impossibility to the PLR maneuver (lower limb amputation, respiratory intolerance).
- Patient with poor echogenicity noted previously.
- Patient protected by law.
- Investigation Plan:
Patients meeting the inclusion criteria and not presenting any non-inclusion criteria may be included. The patient will be informed, or his/her relatives if he/she is unable to express their will, of the objectives and the progress of the study. If the patient, or his/her relatives, does not object to participate to the study, the course of the study will be as follows:
- The following measurements will be performed before and after the PLR test in spontaneously breathing patients (SB) to evaluate the preload dependency:
- Hemodynamic data: systolic (SAP), diastolic (DAP), mean (MAP), Pulse Pressure (PP), Heart Rate (HR), value of the Pulse Pressure Variation (PPV), Cardiac Index (CI) if cardiac output monitoring is already present.
- Echographic data including: time-velocity integral of sub-aortic flow VTI Sub AO); aortic outflow chamber diameter (Diam outflow tract); data from the transmitral pulsed Doppler as well as the data from the tissue Doppler at the mitral annulus (E wave velocity; A wave; E' wave); left ventricular end-diastolic surface.
- Collection of demographic parameters (age, sex, comorbidities), acute pathology and severity scores (SAPSII, APACHE II, SOFA) in the patient file.
- Collection of oxygenation parameters: mode, Fio2 level od pressure support and of PEEP, in addition to the tidal volume and RR.
- Being tested
- Detection of preload responders by a PLR test
- Keywords
- Pulse Pressure, Pulse Pressure Variation, Passive Leg Raising, Echocardiography, Preload dependency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Detection of preload responders by a PLR testOther
Detection of preload dependency by using PLR test and echocardiography
| Study group | Role | What they receive |
|---|---|---|
| Positive PLR test (PLR +) | * Patient over 18 years old.
* Hospitalized in intensive care.
* For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of:
* Acute circulatory failure with mean arterial pressure < 65mmHg or < 30mmHg of its baseline value for hypertensive patients.
* And/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia) :
* In mechanically ventilated patients under spontaneous mode.
* Previously equipped with an arterial catheter. Receives: Other: Detection of preload responders by a PLR test | |
| Negative PLR test (PLR-) | * Patient over 18 years old.
* Hospitalized in intensive care.
* For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of:
* Acute circulatory failure with mean arterial pressure < 65mmHg or < 30mmHg of its baseline value for hypertensive patients.
* And/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia) :
* In mechanically ventilated patients under spontaneous mode.
* Previously equipped with an arterial catheter. Receives: Other: Detection of preload responders by a PLR test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic performance of the decrease in Pulse Pressure Variation (PPV) during a Passive Leg Raising test (PLR) to predict preload responsiveness
To assess the diagnostic performance of the decrease in Pulse Pressure Variation (PPV) during a Passive Leg Raising test (PLR) to predict preload responsiveness in mechanically ventilated patients under spontaneous mode hospitalized in intensive care. PPV, baseline values will be collected before passive leg raising (as displayed by our routine monitoring devices) and at one minute of the PLR manoeuvre. The difference between these two parameters will be calculated and entered into our database for each patient and a ROC curve analysis of this new parameter will be performed within a binary classification model by plotting the True Positive Rate (TPR) against the False Positive Rate (FPR) at different threshold settings. This will give us the ability of this new parameter to discriminate patients who are preload responders from those who are not, and ultimately a new cut-off value.
Measured: Day 1
Secondary outcomes (2)
Evaluate the diagnostic performance of the increase in pulse pressure (PP) during a PLR test to predict preload responsiveness
Evaluate the diagnostic performance of the increase in pulse pressure (PP) during a PLR test to predict preload responsiveness in mechanically ventilated patients under spontaneous mode hospitalized in intensive care. For this PP, baseline values will be calculated as the difference between the systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) before passive leg raising and at one minute of the PLR maneuver. The difference between these two parameters (at baseline and at one minute of the PLR maneuver) will be calculated and entered into our database for each patient and a ROC curve analysis of this new parameter will be performed in order to give us the ability of this new parameter to discriminate patients who are preload responders from those who are not, and ultimately a new cut-off value.
Measured: Day 1
Compare PLR measurements other hemodynamic data
Compare before/after PLR measurements other hemodynamic data (Blood pressure, cardiac output, heart rate). Differences between baseline parameters (SAP, DAP, MAP, Cardiac output and HR) and at one minute PLR maneuver will be calculated and ROC curve analysis of this new parameter will be performed in order to give us the ability of this new parameter to discriminate patients who are preload responders from those who are not, and ultimately a new cut-off value.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2024
- Study start29 Jan 2024
- Primary completion27 Mar 2025
- Study completion27 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for General Critically Ill Patients With HypovolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- CHU de Reims
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06495489
- Sponsor's protocol ID
- PO23139
- Status last verified
- Jul 2025
- First submitted
- 10 Jun 2024
- Last updated
- 9 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Shi R, Moretto F, Prat D, Jacobs F, Teboul JL, Hamzaoui O. Dynamic changes of pulse pressure but not of pulse pressure variation during passive leg raising predict preload responsiveness in critically ill patients with spontaneous breathing activity. J Crit Care. 2022 Dec;72:154141. doi: 10.1016/j.jcrc.2022.154141. Epub 2022 Sep 15.
PubMed 36116288Hamzaoui O, Shi R, Carelli S, Sztrymf B, Prat D, Jacobs F, Monnet X, Gouezel C, Teboul JL. Changes in pulse pressure variation to assess preload responsiveness in mechanically ventilated patients with spontaneous breathing activity: an observational study. Br J Anaesth. 2021 Oct;127(4):532-538. doi: 10.1016/j.bja.2021.05.034. Epub 2021 Jul 8.
PubMed 34246460
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Performance of Changes of Pulse Pressure and of Pulse Pressure Variation to Detect Preload Responsiveness in Mechanically Ventilated Patients Under a Spontaneous Mode
- ClinicalTrials.gov ID
- NCT06495489
- Acronym / sponsor ID
- PO23139
- Keywords
- Pulse Pressure, Pulse Pressure Variation, Passive Leg Raising, Echocardiography, Preload dependency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- CHU de ReimsUniversity, hospital or other
- Study start
- 29 Jan 2024 (actual)
- Primary completion
- 27 Mar 2025 (actual)
- Study completion
- 27 Mar 2025 (actual)
- First posted
- 10 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The management of septic shock patients includes the infusion of fluids, however fluids may be deleterious if the patient does not respond by increasing cardiac output. By consequence, it is now recommended to predict the fluid response (fluid or preload responsiveness) before infusing them. In this protocol, the investigators will include critically ill patients mechanically ventilated patients under a spontaneous mode, for whom the physician in charge has decided to test preload responsiveness. The investigators will collect from the continuous monitoring of arterial pressure of the patient the Pulse Pressure (PP) which is the difference between systolic arterial pressure and diastolic arterial pressure and the Pulse Pressure Variation (PPV) automatically displayed by the monitor in addition to other clinical (hemodynamic, respiratory) parameters. After one minute of Passive Leg Raising manoeuvre (PLR) the investigators collect the same parameters and the investigators will compare the changes of these parameters in patients who are preload responsive to patients who are not. Preload responsiveness will be defined by echocardiographic parameters before and during PLR. More exactly, a surrogate of cardiac output measured by echocardiography wich is VTI of the sub-aorti flow; an increase of more than 12% defines apreload responsive patient.
Detailed description
*Objectives:
Primary : to assess the diagnostic performance of the decrease in Pulse Pressure Variation (PPV) during a Passive Leg Raising test (PLR) to predict preload responsiveness in mechanically ventilated patients under spontaneous mode hospitalized in intensive care.
Secondary:
- Evaluate the diagnostic performance of the increase in Pulse Pressure (PP) during a PLR test to predict preload responsiveness in this same population.
- Compare before/after PLR measurements other hemodynamic data (blood pressure, cardiac output, heart rate).
- Experimental scheme: it is a diagnostic and monocentric study.
- Population / patients:
Inclusion criteria:
- Patient over 18 years old.
- Hospitalized in intensive care.
- For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of:
- Acute circulatory failure with mean arterial pressure < 65mmHg or < 30mmHg of its baseline value for hypertensive patients.
- And/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia).
- In mechanically ventilated patients under spontaneous mode.
- Previously equipped with an arterial catheter.
- Affiliated to a social security scheme.
Non-inclusion criteria:
- Patient with arrythmia (PPV is not applicable).
- Patient with intra-abdominal hypertension (PLR test is not valid).
- Patient with a contraindication/impossibility to the PLR maneuver (lower limb amputation, respiratory intolerance).
- Patient with poor echogenicity noted previously.
- Patient protected by law.
- Investigation Plan:
Patients meeting the inclusion criteria and not presenting any non-inclusion criteria may be included. The patient will be informed, or his/her relatives if he/she is unable to express their will, of the objectives and the progress of the study. If the patient, or his/her relatives, does not object to participate to the study, the course of the study will be as follows:
- The following measurements will be performed before and after the PLR test in spontaneously breathing patients (SB) to evaluate the preload dependency:
- Hemodynamic data: systolic (SAP), diastolic (DAP), mean (MAP), Pulse Pressure (PP), Heart Rate (HR), value of the Pulse Pressure Variation (PPV), Cardiac Index (CI) if cardiac output monitoring is already present.
- Echographic data including: time-velocity integral of sub-aortic flow VTI Sub AO); aortic outflow chamber diameter (Diam outflow tract); data from the transmitral pulsed Doppler as well as the data from the tissue Doppler at the mitral annulus (E wave velocity; A wave; E' wave); left ventricular end-diastolic surface.
- Collection of demographic parameters (age, sex, comorbidities), acute pathology and severity scores (SAPSII, APACHE II, SOFA) in the patient file.
- Collection of oxygenation parameters: mode, Fio2 level od pressure support and of PEEP, in addition to the tidal volume and RR.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Positive PLR test (PLR +) | – | Other: Detection of preload responders by a PLR test* Patient over 18 years old. * Hospitalized in intensive care. * For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of: * Acute circulatory failure with mean arterial pressure < 65mmHg or < 30mmHg of its baseline value for hypertensive patients. * And/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia) : * In mechanically ventilated patients under spontaneous mode. * Previously equipped with an arterial catheter. |
| Negative PLR test (PLR-) | – | Other: Detection of preload responders by a PLR test* Patient over 18 years old. * Hospitalized in intensive care. * For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of: * Acute circulatory failure with mean arterial pressure < 65mmHg or < 30mmHg of its baseline value for hypertensive patients. * And/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia) : * In mechanically ventilated patients under spontaneous mode. * Previously equipped with an arterial catheter. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * Patient over 18 years old. * Hospitalized in intensive care. * For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of: * Acute circulatory failure with mean arterial pressure < 65mmHg or < 30mmHg of its baseline value for hypertensive patients. * And/or other signs of hemodynamic instability (tachycardia, mottling, oliguria, hyperlactatemia). * In mechanically ventilated patients under spontaneous mode. * Previously equipped with an arterial catheter. * Affiliated to a social security scheme.
Key inclusion criteria (8 listed)
- Patient over 18 years old.
- Hospitalized in intensive care.
- For which the clinician in charge of the patient will need to predict the response to fluids and decide on a possible infusion of fluids, because of:
- In mechanically ventilated patients under spontaneous mode.
- Previously equipped with an arterial catheter.
Key exclusion criteria (5 listed)
- Patient with arrythmia (PPV is not applicable).
- Patient with intra-abdominal hypertension (PLR test is not valid).
- Patient with a contraindication/impossibility to the PLR maneuver (lower limb amputation, respiratory intolerance).
- Patient with poor echogenicity noted previously.
- Patient protected by law.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Detection of preload responders by a PLR testDetection of preload dependency by using PLR test and echocardiography | Other | Negative PLR test (PLR-), Positive PLR test (PLR +) |
Primary outcome
Diagnostic performance of the decrease in Pulse Pressure Variation (PPV) during a Passive Leg Raising test (PLR) to predict preload responsiveness
Time frame: Day 1
To assess the diagnostic performance of the decrease in Pulse Pressure Variation (PPV) during a Passive Leg Raising test (PLR) to predict preload responsiveness in mechanically ventilated patients under spontaneous mode hospitalized in intensive care. PPV, baseline values will be collected before passive leg raising (as displayed by our routine monitoring devices) and at one minute of the PLR manoeuvre. The difference between these two parameters will be calculated and entered into our database for each patient and a ROC curve analysis of this new parameter will be performed within a binary classification model by plotting the True Positive Rate (TPR) against the False Positive Rate (FPR) at different threshold settings. This will give us the ability of this new parameter to discriminate patients who are preload responders from those who are not, and ultimately a new cut-off value.
2 secondary outcomes
Evaluate the diagnostic performance of the increase in pulse pressure (PP) during a PLR test to predict preload responsiveness
Time frame: Day 1
Compare PLR measurements other hemodynamic data
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2025.
- Background: PubMed 36116288Shi R, Moretto F, Prat D, Jacobs F, Teboul JL, Hamzaoui O. Dynamic changes of pulse pressure but not of pulse pressure variation during passive leg raising predict preload responsiveness in critically ill patients with spontaneous breathing activity. J Crit Care. 2022 Dec;72:154141. doi: 10.1016/j.jcrc.2022.154141. Epub 2022 Sep 15.
- Background: PubMed 34246460Hamzaoui O, Shi R, Carelli S, Sztrymf B, Prat D, Jacobs F, Monnet X, Gouezel C, Teboul JL. Changes in pulse pressure variation to assess preload responsiveness in mechanically ventilated patients with spontaneous breathing activity: an observational study. Br J Anaesth. 2021 Oct;127(4):532-538. doi: 10.1016/j.bja.2021.05.034. Epub 2021 Jul 8.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of General Critically Ill Patients With Hypovolemia, run by CHU de Reims at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic performance of the decrease in Pulse Pressure Variation (PPV) during a Passive Leg Raising test (PLR) to predict preload responsiveness (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06495489, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2025; AzTrials last refreshed its copy on 31 Oct 2026.