Hemodynamic InstabilityNCT07304661
Comparison of PPV and LVOT VTI During Passive Leg Raising to Predict Fluid Responsiveness
An observational study of Hemodynamic Instability and Hypovolemia, run by Izmir Katip Celebi University at 1 site in Turkey (Türkiye).
Trial summary
Hemodynamic instability remains one of the leading causes of morbidity and mortality among critically ill patients in intensive care units. One major contributor to this instability is intravascular fluid deficit. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemodynamic Instability, Hypovolemia, Critical Illness
- How many people
- 48 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Jan 2026to 1 Jun 2027
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: The study population consists of adult critically ill patients admitted to the Intensive Care Unit (ICU) who are receiving mechanical ventilation support. Eligible participants are those identified by the intensive care team as having a suspected intravascular fluid deficit, for whom a fluid responsiveness assessment is clinically indicated. The cohort specifically targets patients undergoing the Passive Leg Raising (PLR) maneuver as part of routine standard practice, where invasive arterial monitoring is available to record Pulse Pressure Variation (PPV).
Who may be able to join
- Adult patients aged ≥18 years
- Patients admitted to the intensive care unit receiving mechanical ventilation
- Presence of suspected intravascular fluid deficit (hypotension, negative fluid balance, or clinical signs of peripheral hypoperfusion)
- Patients in sinus rhythm
- Presence of invasive arterial blood pressure monitoring
- Adequate echocardiographic window allowing transthoracic echocardiographic measurement of LVOT VTI
- Patients ventilated with tidal volume ≥8 mL/kg (ideal body weight)
- Hemodynamically stable enough to allow measurement
Who cannot join
- Patients under 18 years of age
- Presence of atrial fibrillation or significant arrhythmias such as frequent ventricular or atrial ectopy
- Severe right ventricular dysfunction or significant tricuspid regurgitation
- Advanced aortic valve disease (severe stenosis or severe regurgitation)
- Patients with significant spontaneous breathing effort
- Patients receiving lung-protective low tidal volume ventilation strategy (<8 mL/kg) due to ARDS
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- Inadequate echocardiographic window for LVOT VTI assessment
- Severe hemodynamic instability during measurement (sudden vasopressor escalation or need for resuscitation)
- Patients who refuse to participate or from whom written informed consent cannot be obtained from themselves or a first-degree relative
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Izmir Katip Celebi University Atatürk Training and Research Hospital İzmir, , Turkey
Izmir
Elif Ersüs, M.D., +90 537 944 60 59, elifersus@gmail.com
About this study
Official title: Comparison of Pulse Pressure Variation and LVOT VTI-Based Cardiac Output Changes During Passive Leg Raising Maneuver in Predicting Fluid Responsiveness in Mechanically Ventilated Critically Ill Patients: A Prospective Observational Study
Hemodynamic instability remains one of the leading causes of morbidity and mortality among critically ill patients in intensive care units. One major contributor to this instability is intravascular fluid deficit. Although fluid administration is often preferred as an initial intervention, inaccurate estimation of fluid requirements carries significant risks. Inadequate resuscitation may lead to tissue hypoperfusion and organ dysfunction, whereas excessive fluid loading is associated with pulmonary edema, increased intra-abdominal pressure, multi-organ dysfunction, and increased mortality. Consequently, reliable prediction of fluid responsiveness is considered a critical determinant in modern intensive care management.
The limited reliability of static parameters in predicting fluid responsiveness and the fact that PPV retains its validity only under specific clinical conditions highlight the need for more effective methods. In recent years, hemodynamic changes assessed during the passive leg raising (PLR) maneuver have gained prominence; particularly, left ventricular outflow tract velocity time integral (LVOT VTI)-based cardiac output measurements have been identified as a strong parameter for predicting fluid responsiveness . Moreover, changes in pulse pressure variation (PPV) during PLR have also been reported as a potential predictor; however, the number of studies prospectively comparing PPV variation and LVOT VTI-based cardiac output change within the same patient population remains limited . Therefore, the proposed study aims to fill this gap in the literature and contribute to fluid management in the intensive care setting.
The aim of this study is to compare the performance of PPV variation and LVOT VTI-based cardiac output change after the PLR maneuver in predicting fluid responsiveness among mechanically ventilated critically ill patients, and to determine the diagnostic value of both methods. The findings of the present study are expected to support more reliable decision-making in fluid therapy and provide clinical evidence toward the individualization of fluid management in intensive care practice.
Read the detailed description
This study is designed as a prospective observational trial. No additional intervention, procedure, or treatment beyond standard clinical practice will be performed. All data will be obtained during routine clinical management in our intensive care unit.
In mechanically ventilated patients with suspected fluid deficit, the passive leg raising (PLR) maneuver is applied as part of standard practice, during which changes in pulse pressure variation (PPV) are recorded by invasive arterial monitoring.
In this observational study, transthoracic echocardiographic (TTE) measurements of LVOT VTI will be performed by an experienced operator in addition to routine practice. Using pulse wave Doppler (PW), LVOT VTI will be recorded, and stroke volume (SV) and cardiac output (CO) will be calculated by multiplying the LVOT VTI value by the LVOT diameter. Consequently, changes in PPV and LVOT VTI-based CO during PLR will be compared.
Following TTE measurements of LVOT VTI and LVOT diameter in both the semi-recumbent position (45°) and immediately after PLR, SV and CO will be calculated. Based on these measurements, patients will be allocated into two groups:
- Fluid responsive: Patients showing ≥10% increase in LVOT VTI-based CO following PLR
- Non-fluid responsive: Patients showing <10% change in LVOT VTI-based CO following PLR
After grouping patients accordingly, PPV changes during PLR will be compared between the two groups. This will allow evaluation of the predictive performance of PPV variation relative to LVOT VTI-based CO change in determining fluid responsiveness. All measurements will be performed by an experienced clinician without disrupting standard patient care. No additional fluid loading, invasive procedures, or therapeutic interventions will be undertaken throughout the study.
The primary aim is to compare the diagnostic performance of PPV variation and LVOT VTI-based cardiac output changes following a PLR maneuver in predicting fluid responsiveness. The study seeks to determine the diagnostic value of both methods to support more individualised fluid management.
The recorded data will include:
- Pre- and post-PLR LVOT VTI, stroke volume, cardiac output, and PPV values
- Routine monitoring parameters (systolic/diastolic blood pressure, mean arterial pressure, heart rate, and SpO₂)
- Demographic characteristics (age, sex, comorbidities) retrieved through the hospital database
Informed consent will be obtained from all participating patients or their legally authorized representatives.
- Keywords
- Fluid Responsiveness, Passive Leg Raising, Pulse Pressure Variation, LVOT VTI, Cardiac Output, Echocardiography
- Medical subject headings
- Hypovolemia, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Fluid Responders | Defined as an increase in LVOT VTI-based Cardiac Output (CO) of ≥ 10% from baseline. | |
| Fluid Non-Responders | Defined as an increase in LVOT VTI-based Cardiac Output (CO) of < 10% from baseline. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pulse Pressure Variation (Delta PPV)
Pulse Pressure Variation (PPV) is recorded via invasive arterial monitoring at baseline (T0, semi-sitting) and during the Passive Leg Raising maneuver (T1).
Measured: Baseline (T0) and between 60 seconds after the PLR maneuver.
Secondary outcomes (4)
Percentage Change in Cardiac Output (Delta CO)
Cardiac Output (CO) is calculated using the Left Ventricular Outflow Tract Velocity Time Integral (LVOT VTI) and the LVOT diameter measured via transthoracic echocardiography.
Measured: Baseline (T0) and between 60 seconds after the PLR maneuver.
Correlation between Delta PPV and Delta CO
Correlation Coefficient (r) between PPV Change and Cardiac Output Change
Measured: Baseline (T0) and between 60 seconds after the PLR maneuver.
Hemodynamic Parameter Changes (MAP, HR)
Measurement of changes in mean arterial pressure and heart rate before and after PLR and comparison between groups.
Measured: Baseline (T0) and between 60 seconds after the PLR maneuver.
Diagnostic Accuracy (ROC-AUC, Sensitivity, Specificity, Cut-off)
Evaluation of diagnostic performance of ΔPPV and ΔCO using receiver operating characteristic (ROC) analysis, including AUC, optimal cut-off value, sensitivity, and specificity for predicting fluid responsiveness.
Measured: Baseline (T0) and between 60 seconds after the PLR maneuver.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2025
- Study start1 Jan 2026
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemodynamic InstabilityStudies 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
- 48 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Izmir Katip Celebi University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmet Salih Tüzen, MD, Izmir Katip Celebi University
- Investigators
- Murat Aksun, Principal investigator, Izmir Katip Celebi University Atatürk Training and Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07304661
- Sponsor's protocol ID
- 2025-SAEK-0811
- Status last verified
- Nov 2026
- First submitted
- 13 Dec 2025
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: All data necessary to support the study protocol, including de-identified individual participant data (IPD) related to study protocol, and primary and secondary outcome measures, will be made available upon reasonable request from qualified researchers for academic purposes, in accordance with institutional and ethical guidelines.
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Pulse Pressure Variation and LVOT VTI-Based Cardiac Output Changes During Passive Leg Raising Maneuver in Predicting Fluid Responsiveness in Mechanically Ventilated Critically Ill Patients: A Prospective Observational Study
- ClinicalTrials.gov ID
- NCT07304661
- Acronym / sponsor ID
- 2025-SAEK-0811
- Keywords
- Fluid Responsiveness, Passive Leg Raising, Pulse Pressure Variation, LVOT VTI, Cardiac Output, Echocardiography
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Izmir Katip Celebi UniversityUniversity, hospital or other
- Study start
- 1 Jan 2026 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 26 Dec 2025 (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.
Hemodynamic instability remains one of the leading causes of morbidity and mortality among critically ill patients in intensive care units. One major contributor to this instability is intravascular fluid deficit. Although fluid administration is often preferred as an initial intervention, inaccurate estimation of fluid requirements carries significant risks. Inadequate resuscitation may lead to tissue hypoperfusion and organ dysfunction, whereas excessive fluid loading is associated with pulmonary edema, increased intra-abdominal pressure, multi-organ dysfunction, and increased mortality. Consequently, reliable prediction of fluid responsiveness is considered a critical determinant in modern intensive care management.
The limited reliability of static parameters in predicting fluid responsiveness and the fact that PPV retains its validity only under specific clinical conditions highlight the need for more effective methods. In recent years, hemodynamic changes assessed during the passive leg raising (PLR) maneuver have gained prominence; particularly, left ventricular outflow tract velocity time integral (LVOT VTI)-based cardiac output measurements have been identified as a strong parameter for predicting fluid responsiveness . Moreover, changes in pulse pressure variation (PPV) during PLR have also been reported as a potential predictor; however, the number of studies prospectively comparing PPV variation and LVOT VTI-based cardiac output change within the same patient population remains limited . Therefore, the proposed study aims to fill this gap in the literature and contribute to fluid management in the intensive care setting.
The aim of this study is to compare the performance of PPV variation and LVOT VTI-based cardiac output change after the PLR maneuver in predicting fluid responsiveness among mechanically ventilated critically ill patients, and to determine the diagnostic value of both methods. The findings of the present study are expected to support more reliable decision-making in fluid therapy and provide clinical evidence toward the individualization of fluid management in intensive care practice.
Detailed description
This study is designed as a prospective observational trial. No additional intervention, procedure, or treatment beyond standard clinical practice will be performed. All data will be obtained during routine clinical management in our intensive care unit.
In mechanically ventilated patients with suspected fluid deficit, the passive leg raising (PLR) maneuver is applied as part of standard practice, during which changes in pulse pressure variation (PPV) are recorded by invasive arterial monitoring.
In this observational study, transthoracic echocardiographic (TTE) measurements of LVOT VTI will be performed by an experienced operator in addition to routine practice. Using pulse wave Doppler (PW), LVOT VTI will be recorded, and stroke volume (SV) and cardiac output (CO) will be calculated by multiplying the LVOT VTI value by the LVOT diameter. Consequently, changes in PPV and LVOT VTI-based CO during PLR will be compared.
Following TTE measurements of LVOT VTI and LVOT diameter in both the semi-recumbent position (45°) and immediately after PLR, SV and CO will be calculated. Based on these measurements, patients will be allocated into two groups:
- Fluid responsive: Patients showing ≥10% increase in LVOT VTI-based CO following PLR
- Non-fluid responsive: Patients showing <10% change in LVOT VTI-based CO following PLR
After grouping patients accordingly, PPV changes during PLR will be compared between the two groups. This will allow evaluation of the predictive performance of PPV variation relative to LVOT VTI-based CO change in determining fluid responsiveness. All measurements will be performed by an experienced clinician without disrupting standard patient care. No additional fluid loading, invasive procedures, or therapeutic interventions will be undertaken throughout the study.
The primary aim is to compare the diagnostic performance of PPV variation and LVOT VTI-based cardiac output changes following a PLR maneuver in predicting fluid responsiveness. The study seeks to determine the diagnostic value of both methods to support more individualised fluid management.
The recorded data will include:
- Pre- and post-PLR LVOT VTI, stroke volume, cardiac output, and PPV values
- Routine monitoring parameters (systolic/diastolic blood pressure, mean arterial pressure, heart rate, and SpO₂)
- Demographic characteristics (age, sex, comorbidities) retrieved through the hospital database
Informed consent will be obtained from all participating patients or their legally authorized representatives.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Day
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluid Responders | – | –Defined as an increase in LVOT VTI-based Cardiac Output (CO) of ≥ 10% from baseline. |
| Fluid Non-Responders | – | –Defined as an increase in LVOT VTI-based Cardiac Output (CO) of < 10% from baseline. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population consists of adult critically ill patients admitted to the Intensive Care Unit (ICU) who are receiving mechanical ventilation support. Eligible participants are those identified by the intensive care team as having a suspected intravascular fluid deficit, for whom a fluid responsiveness assessment is clinically indicated. The cohort specifically targets patients undergoing the Passive Leg Raising (PLR) maneuver as part of routine standard practice, where invasive arterial monitoring is available to record Pulse Pressure Variation (PPV).
Key inclusion criteria (8 listed)
- Adult patients aged ≥18 years
- Patients admitted to the intensive care unit receiving mechanical ventilation
- Presence of suspected intravascular fluid deficit (hypotension, negative fluid balance, or clinical signs of peripheral hypoperfusion)
- Patients in sinus rhythm
- Presence of invasive arterial blood pressure monitoring
Key exclusion criteria (9 listed)
- Patients under 18 years of age
- Presence of atrial fibrillation or significant arrhythmias such as frequent ventricular or atrial ectopy
- Severe right ventricular dysfunction or significant tricuspid regurgitation
- Advanced aortic valve disease (severe stenosis or severe regurgitation)
- Patients with significant spontaneous breathing effort
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in Pulse Pressure Variation (Delta PPV)
Time frame: Baseline (T0) and between 60 seconds after the PLR maneuver.
Pulse Pressure Variation (PPV) is recorded via invasive arterial monitoring at baseline (T0, semi-sitting) and during the Passive Leg Raising maneuver (T1).
4 secondary outcomes
Percentage Change in Cardiac Output (Delta CO)
Time frame: Baseline (T0) and between 60 seconds after the PLR maneuver.
Correlation between Delta PPV and Delta CO
Time frame: Baseline (T0) and between 60 seconds after the PLR maneuver.
Hemodynamic Parameter Changes (MAP, HR)
Time frame: Baseline (T0) and between 60 seconds after the PLR maneuver.
Diagnostic Accuracy (ROC-AUC, Sensitivity, Specificity, Cut-off)
Time frame: Baseline (T0) and between 60 seconds after the PLR maneuver.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Individual participant dataSharing planned: Undecided. All data necessary to support the study protocol, including de-identified individual participant data (IPD) related to study protocol, and primary and secondary outcome measures, will be made available upon reasonable request from qualified researchers for academic purposes, in accordance with institutional and ethical guidelines.
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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.
Murat Aksun principal investigator
Izmir Katip Celebi University Atatürk Training and Research Hospital
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 Hemodynamic Instability and Hypovolemia, run by Izmir Katip Celebi University at 1 site in Turkey (Türkiye).
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 9 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: looking for participants now, as of the sponsor's last update on 4 Nov 2026. 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 Turkey (Türkiye). 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Murat Aksun, M.D. (+90 552 363 16 14, murataksun@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pulse Pressure Variation (Delta PPV) (time frame: Baseline (T0) and between 60 seconds after the PLR maneuver.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Nov 2026.