Circulatory FailureNCT07304648
Role of End-Tidal CO2 During Passive Leg Raising to Predict Fluid Responsiveness in ICU
An observational study of Circulatory Failure and Critical Illness, run by Izmir Katip Celebi University at 1 site in Turkey (Türkiye).
Trial summary
This prospective observational study evaluates whether monitoring changes in exhaled carbon dioxide (End-Tidal CO2 or EtCO2) during a "Passive Leg Raising" (PLR) test can reliably predict fluid responsiveness in critically ill patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Circulatory Failure, Critical Illness, Hypovolemia
- How many people
- 68 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Jan 2026to 1 Jul 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 patients (aged 18 years or older) admitted to the Intensive Care Unit (ICU) of a university hospital. Eligible participants are those who have been receiving mechanical ventilation support for at least 24 hours and have been identified by the primary intensive care team as requiring a fluid responsiveness assessment via a mini fluid challenge. The cohort includes patients with circulatory failure or suspected hypovolemia where fluid resuscitation is clinically indicated. Patients with contraindications to passive leg raising (e.g., intracranial hypertension, deep vein thrombosis), spontaneous breathing, or severe cardiac valve pathologies are excluded.
Who may be able to join
- Patients aged 18 years or older.
- Patients who have been followed in the intensive care unit (ICU) with mechanical ventilation support for at least 24 hours.
- Patients for whom a mini fluid challenge (MFC) is clinically planned by the intensive care team.
- Patients for whom informed consent has been obtained from first-degree relatives or a legal representative.
Who cannot join
- Patients younger than 18 years of age.
- Pregnant patients.
- Patients without consent from first-degree relatives or a legal representative.
- Patients with known deep vein thrombosis (DVT) in the leg veins (risk of embolism during leg raising).
- Patients with pathologies that may cause increased intracranial pressure (e.g., intracranial mass, hemorrhage).
- Patients with uncontrolled hypertension.
Show all 14Show fewer
- Patients with severe cardiac disease (e.g., right heart failure, pulmonary hypertension, advanced valvular pathology).
- Patients with carbon dioxide (CO2) retention.
- Patients who have undergone hip surgery or hip replacement surgery where Passive Leg Raising (PLR) cannot be performed.
- Patients with spontaneous breathing.
- Patients with a probability of high intra-abdominal pressure.
- Patients who cannot lie in a supine position.
- Patients with current peripheral oxygen saturation (SpO2) < 88%.
- Patients on mechanical ventilation requiring pressure support > 16 mmHg or PEEP > 10 mmHg.
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
Izmir
Deniz Özen Öz, M.D., +90 507 042 20 70, dnzozenoz@gmail.com
About this study
Official title: The Role of End-Tidal Carbon Dioxide Changes During Passive Leg Raising in Predicting Fluid Responsiveness for Mechanically Ventilated Patients in the Intensive Care Unit: A Prospective Observational Study
This prospective observational study evaluates whether monitoring changes in exhaled carbon dioxide (End-Tidal CO2 or EtCO2) during a "Passive Leg Raising" (PLR) test can reliably predict fluid responsiveness in critically ill patients.
In the Intensive Care Unit (ICU), fluid management is a critical balance; while fluid is necessary for tissue perfusion, overload can lead to severe complications. Traditional static measurements (like central venous pressure) are often unreliable for guiding therapy. Dynamic tests like PLR are preferred as they simulate a fluid bolus reversibly by shifting blood from the legs to the heart.
Researchers will observe mechanically ventilated patients planned for fluid resuscitation. The study compares the accuracy of non-invasive EtCO2 changes during PLR against a reference standard "Mini Fluid Challenge" (100 mL fluid administration). Fluid responsiveness will be confirmed using echocardiographic measurements (LVOT-VTI) or arterial pressure changes. The goal is to validate EtCO2 as a practical, real-time tool for safe fluid management.
Read the detailed description
Fluid management is the cornerstone of hemodynamic stabilization in ICU patients with circulatory failure. However, distinguishing between patients who will benefit from fluid (responders) and those who will not is vital to prevent the high mortality associated with inappropriate fluid administration.Static parameters (e.g., CVP, MAP) fail to reliably predict fluid responsiveness. Dynamic parameters are superior but have limitations, such as dependence on regular heart rhythm and specific ventilation settings. Consequently, interest has shifted toward non-invasive surrogates for cardiac output, such as End-Tidal CO2 (EtCO2), which tracks pulmonary blood flow changes under constant ventilation. This study investigates whether Delta EtCO2 during a PLR maneuver can accurately predict the response to a fluid challenge. The primary objective is to determine the diagnostic accuracy of Delta EtCO2 during PLR. Its predictive value will be validated against the hemodynamic response to a Mini Fluid Challenge (MFC), serving as the reference method. This prospective, single-center, observational cohort study includes adult patients in the ICU receiving mechanical ventilation who require fluid resuscitation.
Passive Leg Raising (PLR) Test: The patient starts in a semi-recumbent position (45°). They are then moved to a supine position with legs raised to 45° without manual handling to avoid sympathetic stimulation. This auto-transfuses blood from the lower body to the central circulation, increasing preload.
Mini Fluid Challenge (MFC): Following PLR, 100 mL of crystalloid fluid is infused intravenously over approximately 1 minute.
Definition of Fluid Responsiveness (Reference Standard): An increase in Left Ventricular Outflow Tract Velocity Time Integral (LVOT-VTI) of >10% on echocardiography. If cardiac output/VTI cannot be assessed, responsiveness is defined as a Systolic Arterial Pressure increase of > 4%, a Pulse Pressure variation decrease of > 2%, or a Mean Arterial Pressure increase of > 15%.
The sample size was calculated using G*Power 3.1 software based on a pilot study of 6 patients. In the pilot study, Delta EtCO2 values were found to be 3.5±2.1 mmHg in the fluid responder group and 2.1±1.1 mmHg in the non-responder group. Based on these findings, with an effect size (Cohen's d) of 0.72, an alpha error level of 0.05, and a targeted power (1-beta) of 0.80, the required sample size was calculated. Accounting for a potential 10% attrition rate, the study is planned to be conducted with a total of 68 patients.
- Conditions
- Circulatory Failure, Critical Illness, Hypovolemia
- Keywords
- Fluid Responsiveness, Passive Leg Raising, End-Tidal CO2, Mini Fluid Challenge, Mechanical Ventilation, Intensive Care
- Medical subject headings
- Shock, Critical Illness, Hypovolemia
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 | Patients who demonstrate a significant hemodynamic improvement following the Mini Fluid Challenge (MFC. Defined as an increase in Left Ventricular Outflow Tract Velocity Time Integral (LVOT-VTI) of >10%. If VTI unavailable, increase in Systolic Arterial Pressure > 4%, Pulse Pressure variation decrease > 2%, or Mean Arterial Pressure increase > 15%. | |
| Fluid Non-Responders | Patients who do not demonstrate a significant hemodynamic improvement following the Mini Fluid Challenge (MFC). Defined as an increase in LVOT-VTI of < 10% (or failure to meet the alternative blood pressure criteria). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in End-Tidal Carbon Dioxide (Delta EtCO2) during Passive Leg Raising (PLR)
The absolute difference in End-Tidal CO2 (EtCO2) levels will be calculated between the baseline measurement (T0, patient semi-recumbent at 45°) and the measurement taken during the Passive Leg Raising test (T1, patient supine with legs raised to 45°). The diagnostic accuracy of this Delta EtCO2 will be evaluated by comparing it against the patient's fluid responsiveness status (Responder vs. Non-Responder) determined by the subsequent Mini Fluid Challenge.
Measured: Measured between 60 to 90 seconds after the position change.
Secondary outcomes (6)
Change in Arterial Blood Pressures (SAP, DAP, MAP)
Systolic (SAP), Diastolic (DAP), and Mean Arterial Pressure (MAP) will be monitored at baseline (T0) and during the PLR maneuver (T1). The changes in these pressures will be compared between the fluid responder and non-responder groups.
Measured: Measured between 60 to 90 seconds after the position change.
Change in Heart Rate (Delta HR)
Heart rate will be monitored at baseline (T0) and during the PLR maneuver (T1). The absolute change (Delta HR) will be compared between the fluid responder and non-responder groups.
Measured: Measured between 60 to 90 seconds after the position change.
Change in Pulse Pressure Variation (Delta PPV)
Pulse Pressure Variation (PPV) will be monitored at baseline (T0) and during the PLR maneuver (T1). The change in PPV will be compared between the fluid responder and non-responder groups.
Measured: Measured between 60 to 90 seconds after the position change.
Change in Oxygen Saturation (Delta SO2)
Oxygen Saturation (SO2) will be monitored at baseline (T0) and during the PLR maneuver (T1). The change will be compared between the fluid responder and non-responder groups.
Measured: Measured between 60 to 90 seconds after the position change.
Change in Vena Cava Inferior (VCI) Distensibility Index
The VCI diameter will be measured using ultrasonography during inspiration and expiration at baseline (T0) and during the PLR maneuver (T1). The VCI distensibility index will be calculated and its change compared between the groups.
Measured: Measured between 60 to 90 seconds after the position change.
Change in Left Ventricular Outflow Tract Velocity Time Integral (LVOT-VTI)
This is the reference standard used to classify patients. Following the Mini Fluid Challenge (100ml crystalloid over 1 min), the percentage change in LVOT-VTI is measured. An increase of >10% defines the patient as a "Fluid Responder".
Measured: Immediately following the 1-minute Mini Fluid Challenge.
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 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Circulatory FailureStudies 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
- 68 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, M.D., Principal investigator, Izmir Katip Celebi University Atatürk Training and Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07304648
- Sponsor's protocol ID
- 2025-SAEK-0807
- 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
- The Role of End-Tidal Carbon Dioxide Changes During Passive Leg Raising in Predicting Fluid Responsiveness for Mechanically Ventilated Patients in the Intensive Care Unit: A Prospective Observational Study
- ClinicalTrials.gov ID
- NCT07304648
- Acronym / sponsor ID
- 2025-SAEK-0807
- Conditions
- Circulatory Failure, Critical Illness, Hypovolemia
- Keywords
- Fluid Responsiveness, Passive Leg Raising, End-Tidal CO2, Mini Fluid Challenge, Mechanical Ventilation, Intensive Care
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 68 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 Jul 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.
This prospective observational study evaluates whether monitoring changes in exhaled carbon dioxide (End-Tidal CO2 or EtCO2) during a "Passive Leg Raising" (PLR) test can reliably predict fluid responsiveness in critically ill patients.
In the Intensive Care Unit (ICU), fluid management is a critical balance; while fluid is necessary for tissue perfusion, overload can lead to severe complications. Traditional static measurements (like central venous pressure) are often unreliable for guiding therapy. Dynamic tests like PLR are preferred as they simulate a fluid bolus reversibly by shifting blood from the legs to the heart.
Researchers will observe mechanically ventilated patients planned for fluid resuscitation. The study compares the accuracy of non-invasive EtCO2 changes during PLR against a reference standard "Mini Fluid Challenge" (100 mL fluid administration). Fluid responsiveness will be confirmed using echocardiographic measurements (LVOT-VTI) or arterial pressure changes. The goal is to validate EtCO2 as a practical, real-time tool for safe fluid management.
Detailed description
Fluid management is the cornerstone of hemodynamic stabilization in ICU patients with circulatory failure. However, distinguishing between patients who will benefit from fluid (responders) and those who will not is vital to prevent the high mortality associated with inappropriate fluid administration.Static parameters (e.g., CVP, MAP) fail to reliably predict fluid responsiveness. Dynamic parameters are superior but have limitations, such as dependence on regular heart rhythm and specific ventilation settings. Consequently, interest has shifted toward non-invasive surrogates for cardiac output, such as End-Tidal CO2 (EtCO2), which tracks pulmonary blood flow changes under constant ventilation. This study investigates whether Delta EtCO2 during a PLR maneuver can accurately predict the response to a fluid challenge. The primary objective is to determine the diagnostic accuracy of Delta EtCO2 during PLR. Its predictive value will be validated against the hemodynamic response to a Mini Fluid Challenge (MFC), serving as the reference method. This prospective, single-center, observational cohort study includes adult patients in the ICU receiving mechanical ventilation who require fluid resuscitation.
Passive Leg Raising (PLR) Test: The patient starts in a semi-recumbent position (45°). They are then moved to a supine position with legs raised to 45° without manual handling to avoid sympathetic stimulation. This auto-transfuses blood from the lower body to the central circulation, increasing preload.
Mini Fluid Challenge (MFC): Following PLR, 100 mL of crystalloid fluid is infused intravenously over approximately 1 minute.
Definition of Fluid Responsiveness (Reference Standard): An increase in Left Ventricular Outflow Tract Velocity Time Integral (LVOT-VTI) of >10% on echocardiography. If cardiac output/VTI cannot be assessed, responsiveness is defined as a Systolic Arterial Pressure increase of > 4%, a Pulse Pressure variation decrease of > 2%, or a Mean Arterial Pressure increase of > 15%.
The sample size was calculated using G*Power 3.1 software based on a pilot study of 6 patients. In the pilot study, Delta EtCO2 values were found to be 3.5±2.1 mmHg in the fluid responder group and 2.1±1.1 mmHg in the non-responder group. Based on these findings, with an effect size (Cohen's d) of 0.72, an alpha error level of 0.05, and a targeted power (1-beta) of 0.80, the required sample size was calculated. Accounting for a potential 10% attrition rate, the study is planned to be conducted with a total of 68 patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Day
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluid Responders | – | –Patients who demonstrate a significant hemodynamic improvement following the Mini Fluid Challenge (MFC. Defined as an increase in Left Ventricular Outflow Tract Velocity Time Integral (LVOT-VTI) of >10%. If VTI unavailable, increase in Systolic Arterial Pressure > 4%, Pulse Pressure variation decrease > 2%, or Mean Arterial Pressure increase > 15%. |
| Fluid Non-Responders | – | –Patients who do not demonstrate a significant hemodynamic improvement following the Mini Fluid Challenge (MFC). Defined as an increase in LVOT-VTI of < 10% (or failure to meet the alternative blood pressure criteria). |
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 patients (aged 18 years or older) admitted to the Intensive Care Unit (ICU) of a university hospital. Eligible participants are those who have been receiving mechanical ventilation support for at least 24 hours and have been identified by the primary intensive care team as requiring a fluid responsiveness assessment via a mini fluid challenge. The cohort includes patients with circulatory failure or suspected hypovolemia where fluid resuscitation is clinically indicated. Patients with contraindications to passive leg raising (e.g., intracranial hypertension, deep vein thrombosis), spontaneous breathing, or severe cardiac valve pathologies are excluded.
Key inclusion criteria (4 listed)
- Patients aged 18 years or older.
- Patients who have been followed in the intensive care unit (ICU) with mechanical ventilation support for at least 24 hours.
- Patients for whom a mini fluid challenge (MFC) is clinically planned by the intensive care team.
- Patients for whom informed consent has been obtained from first-degree relatives or a legal representative.
Key exclusion criteria (14 listed)
- Patients younger than 18 years of age.
- Pregnant patients.
- Patients without consent from first-degree relatives or a legal representative.
- Patients with known deep vein thrombosis (DVT) in the leg veins (risk of embolism during leg raising).
- Patients with pathologies that may cause increased intracranial pressure (e.g., intracranial mass, hemorrhage).
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 End-Tidal Carbon Dioxide (Delta EtCO2) during Passive Leg Raising (PLR)
Time frame: Measured between 60 to 90 seconds after the position change.
The absolute difference in End-Tidal CO2 (EtCO2) levels will be calculated between the baseline measurement (T0, patient semi-recumbent at 45°) and the measurement taken during the Passive Leg Raising test (T1, patient supine with legs raised to 45°). The diagnostic accuracy of this Delta EtCO2 will be evaluated by comparing it against the patient's fluid responsiveness status (Responder vs. Non-Responder) determined by the subsequent Mini Fluid Challenge.
6 secondary outcomes
Change in Arterial Blood Pressures (SAP, DAP, MAP)
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Heart Rate (Delta HR)
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Pulse Pressure Variation (Delta PPV)
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Oxygen Saturation (Delta SO2)
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Vena Cava Inferior (VCI) Distensibility Index
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Left Ventricular Outflow Tract Velocity Time Integral (LVOT-VTI)
Time frame: Immediately following the 1-minute Mini Fluid Challenge.
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, M.D. 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 Circulatory Failure and Critical Illness, 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 4 inclusion and 14 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 End-Tidal Carbon Dioxide (Delta EtCO2) during Passive Leg Raising (PLR) (time frame: Measured between 60 to 90 seconds after the position change.). 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.