SepsisFRESEDICUNCT02679625
Comparison of Non-Invasive Methods of Assessing Fluid Responsiveness in ED and ICU Patients
An observational study of Sepsis and Fluid Overload, run by Olive View-UCLA Education & Research Institute at 1 site in United States.
Trial summary
Accurate assessment of fluid responsiveness (FRes) is central to guiding fluid management in septic and critically ill patients. As evidence accumulates that both inadequate and excessive fluid resuscitation are associated with increased morbidity and mortality, it is simultaneously becoming increasingly clear that… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Sepsis, Fluid Overload, Hypovolemia
- What is being tested?
- Ultrasound and NICOM
- Type of treatment
- Medical device
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2014to 1 Dec 2019
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The investigators will recruit adult patients in the ED and ICU who are septic, have received an initial bolus of 20-30 cc/kg of IV fluid, and there is still a question by the clinical team of whether they are still fluid responsive.
Who may be able to join
- Subjects presenting to the ED will be screened in accordance with the Olive View Medical Center Sepsis Waiver, and subjects meeting two of the following four criteria will be eligible for inclusion in the study: Temperature >38/100.4 or <36/96.8, heart rate >90, respiratory rate >20 or PaCO2<32, and WBC >12K or <4K or > 10% bands (neutrophils). The clinical team will be contacted regarding patients identified based on this initial screening, and if the patient is determined to have a suspected infection and a fluid bolus is planned, the patient will be enrolled in the study if they meet the following criteria:
- Adult between the age of 18 to 90 years old;
- Not pregnant;
- Not using non-invasive positive pressure ventilation (CPAP or BiPAP);
- No history of heart, lung, and/or liver transplant;
- Not determined by the clinical team to be acutely unstable requiring immediate intervention at the time of data collection, and;
- No contraindications to a passive leg raise test (known or suspected cranio-cerebral or C-spine injury, venous thrombosis, orthopedic injury requiring immobilization or traction, or other contraindications as per clinical team).
Who cannot join
- Pregnant;
- Using non-invasive positive pressure ventilation (CPAP or BiPAP);
- Presence of or suspected elevated intracranial pressure;
- Presence of central venous catheters or other medical devices that prevent the use of bedside ultrasound;
- History of heart, lung, and/or liver transplant;
- History of critical aortic stenosis or severe aortic insufficiency;
- Determined by the clinical team to be acutely unstable and requiring immediate intervention at the time of study enrollment or data collection or;
- Has a contraindication to passive leg raise maneuver, e.g. known cervical spinal injury, deep venous thrombosis, orthopedic injury requiring immobilization or traction.
Trial locations and contacts
1 site in 1 country.
About this study
Accurate assessment of fluid responsiveness (FRes) is central to guiding fluid management in septic and critically ill patients. As evidence accumulates that both inadequate and excessive fluid resuscitation are associated with increased morbidity and mortality, it is simultaneously becoming increasingly clear that current widely used methods to predict FRes are of questionable accuracy. The optimal technique to predict FRes would be a non-invasive point-of-care test with not only a high degree of accuracy, but also one which requires minimal training to perform correctly and may be easily performed repeatedly for serial evaluation of FRes during the ongoing management of the critically ill patient.
To date, three major ultrasonographic modalities have emerged as viable candidates for the bedside assessment of FRes: 1) measurement of dynamic changes in inferior vena caval diameter (IVC-CI), 2) measurement of dynamic changes in peripheral arterial waveform derived variables (PA Doppler), and 3) echocardiographic measurement of dynamic changes in left ventricular outflow tract waveform derived variables (LVOT Doppler). In this study, the investigators will perform the first direct comparison of techniques representing all three of the above modalities in the prediction of FRes against a non-invasive bioreactance cardiac output monitor (the Cheetah NICOM™), which has been extensively validated against gold-standard invasive methods of cardiac output measurement. The investigators will compare the accuracy of these modalities in both spontaneously breathing and mechanically ventilated patients using passive leg raise testing (PLR) as a surrogate for volume challenge. In addition, the investigators will also elicit information from the treating physician(s) on their clinical assessment of FRes.
The investigators will recruit adult patients in the ED and ICU with sepsis, who have received an initial bolus of 20-30 cc/kg of IV fluid, and can tolerate the PLR and US procedures. Prior to US and NICOM measurement, investigators will ask the attending physician managing the patient regarding their assessment of the their fluid status. Then, separate investigators will perform US and NICOM measurements independently to ensure blinding. NICOM data, which has been well validated in septic patients, will be shared with the attending physician. They will then be asked if this new data will change management.
Read the detailed description
This is a diagnostic accuracy study comparing selected ultrasound techniques to a well validated standard for predicting fluid responsiveness in septic patients (NICOM). The primary outcomes will be reported in sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios, and receiver operating characteristic curves.
The timeframe for measurement is within 72 hours of the subjects' admission. Determination of the outcome (i.e., whether a subject is fluid responsive) is based upon the data generated by the NICOM device. The NICOM generates data within 5 minutes of assessment. The ultrasound modalities to be studied will generate data within 5 minutes of assessment as well. The US data will be compared to the NICOM data to generate the statistics listed in this protocol. There is no further planned follow-up for the subjects.
- The investigators will compare the ability of dynamic changes in inferior vena caval diameter (IVC-CI), dynamic changes in peripheral arterial waveform derived variables (PA Doppler), and dynamic changes in left ventricular outflow tract waveform derived variables (LVOT Doppler) to detect fluid responsiveness (FRes) relative to FRes as assessed by bioreactance cardiac output monitoring before and after passive leg raise (PLR). Hypothesis: PA Doppler and LVOT Doppler will have superior sensitivity and specificity to predict FRes in comparison to IVC-CI.
- The investigators will evaluate data acquisition duration and data acquisition failure rate of IVC-CI, PA Doppler, and LVOT Doppler. Hypothesis: PA Doppler will have shorter data acquisition durations in comparison to LVOT velocity variation and IVC-CI. Hypothesis: PA Doppler will have lower data acquisition failure rates in comparison to LVOT velocity variation and IVC-CI.
- The investigators will compare the ability of IVC-CI, PA Doppler, and LVOT Doppler to predict FRes in comparison to FRes as predicted by clinical judgment. Hypothesis: PA Doppler and LVOT Doppler will have superior sensitivity and specificity to predict FRes in comparison to clinical judgment.
- The investigators will evaluate the ability of dynamic changes in PA corrected flow times (cFT) to detect FRes relative to FRes as assessed by bioreactance cardiac output monitoring before and after PLR. Hypothesis: cFT will have greatest sensitivity and specificity to predict FRes at a Δflow time threshold of ≥15% after PLR.
Hypothesis: At a Δflow time threshold of ≥15%, cFT will have superior sensitivity and specificity to detect FRes in comparison to IVC-CI.
- Conditions
- Sepsis, Fluid Overload, Hypovolemia
- Being tested
- Ultrasound and NICOM
- Keywords
- Fluid responsiveness, ultrasound
- Medical subject headings
- Sepsis, Edema, Hypovolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrasound and NICOMDevice
All patients enrolled will have all three ultrasound-based modalities for fluid responsiveness performed, as well as have NICOM data to serve as the comparison standard.
What is being measured
The primary outcome is the main question the study is designed to answer.
Fluid responsiveness (measured as cardiac output change, velocity time integral change, or maximal velocity change of greater than 10%, with either passive leg raise maneuver or respiratory variability).
FRes is defined as the ability to predict that subjects who receive a small bolus of 250-500 ml of intravenous fluid will have a rise in their cardiac output or stroke volume of greater than 10%. FRes is a unit-less measurement, as it reflects the percent change in either stroke volume, cardiac index/output, IVC diameter, VTI, or Vmax, as a result of either a passive leg raise or the respiratory cycle. The criterion standard for FRes in this study will be assessed with the NICOM machine. Assessments of FRes using ultrasound-based measures (LVOT, carotid, femoral, and IVC) will be compared to the NICOM-determined assessment of FRes. Analysis is directed at how well the ultrasound-based definitions of FRes perform compared to the NICOM-based assessment.
Measured: Fluid responsiveness is assessed in a three minute interval using the study gold standard, the NICOM. FRes assessment using ultrasound will be performed during this time. One set of measurements will be obtained upon subject admission to the ED or ICU.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2016 (estimated)
- Study start1 Nov 2014
- Primary completion1 Nov 2019
- Study completion1 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies 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
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Olive View-UCLA Education & Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Los Angeles
- Responsible party
- Principal investigator, Alan Chiem, M.D., Olive View-UCLA Education & Research Institute
- Investigators
- Alan Chiem, MD MPH, Principal investigator, Olive View-UCA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02679625
- Sponsor's protocol ID
- IRB #14H-136004
- Acronym
- FRESEDICU
- Status last verified
- Apr 2020
- First submitted
- 26 Nov 2014
- Last updated
- 8 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Non-Invasive Methods of Assessing Fluid Responsiveness in ED and ICU Patients
- ClinicalTrials.gov ID
- NCT02679625
- Acronym / sponsor ID
- FRESEDICU / IRB #14H-136004
- Conditions
- Sepsis, Fluid Overload, Hypovolemia
- Keywords
- Fluid responsiveness, ultrasound
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Olive View-UCLA Education & Research InstituteUniversity, hospital or other
- Collaborators
- University of California, Los Angeles
- Study start
- 1 Nov 2014 (actual)
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 10 Feb 2016 (estimated)
- 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.
Accurate assessment of fluid responsiveness (FRes) is central to guiding fluid management in septic and critically ill patients. As evidence accumulates that both inadequate and excessive fluid resuscitation are associated with increased morbidity and mortality, it is simultaneously becoming increasingly clear that current widely used methods to predict FRes are of questionable accuracy. The optimal technique to predict FRes would be a non-invasive point-of-care test with not only a high degree of accuracy, but also one which requires minimal training to perform correctly and may be easily performed repeatedly for serial evaluation of FRes during the ongoing management of the critically ill patient.
To date, three major ultrasonographic modalities have emerged as viable candidates for the bedside assessment of FRes: 1) measurement of dynamic changes in inferior vena caval diameter (IVC-CI), 2) measurement of dynamic changes in peripheral arterial waveform derived variables (PA Doppler), and 3) echocardiographic measurement of dynamic changes in left ventricular outflow tract waveform derived variables (LVOT Doppler). In this study, the investigators will perform the first direct comparison of techniques representing all three of the above modalities in the prediction of FRes against a non-invasive bioreactance cardiac output monitor (the Cheetah NICOM™), which has been extensively validated against gold-standard invasive methods of cardiac output measurement. The investigators will compare the accuracy of these modalities in both spontaneously breathing and mechanically ventilated patients using passive leg raise testing (PLR) as a surrogate for volume challenge. In addition, the investigators will also elicit information from the treating physician(s) on their clinical assessment of FRes.
The investigators will recruit adult patients in the ED and ICU with sepsis, who have received an initial bolus of 20-30 cc/kg of IV fluid, and can tolerate the PLR and US procedures. Prior to US and NICOM measurement, investigators will ask the attending physician managing the patient regarding their assessment of the their fluid status. Then, separate investigators will perform US and NICOM measurements independently to ensure blinding. NICOM data, which has been well validated in septic patients, will be shared with the attending physician. They will then be asked if this new data will change management.
Detailed description
This is a diagnostic accuracy study comparing selected ultrasound techniques to a well validated standard for predicting fluid responsiveness in septic patients (NICOM). The primary outcomes will be reported in sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios, and receiver operating characteristic curves.
The timeframe for measurement is within 72 hours of the subjects' admission. Determination of the outcome (i.e., whether a subject is fluid responsive) is based upon the data generated by the NICOM device. The NICOM generates data within 5 minutes of assessment. The ultrasound modalities to be studied will generate data within 5 minutes of assessment as well. The US data will be compared to the NICOM data to generate the statistics listed in this protocol. There is no further planned follow-up for the subjects.
- The investigators will compare the ability of dynamic changes in inferior vena caval diameter (IVC-CI), dynamic changes in peripheral arterial waveform derived variables (PA Doppler), and dynamic changes in left ventricular outflow tract waveform derived variables (LVOT Doppler) to detect fluid responsiveness (FRes) relative to FRes as assessed by bioreactance cardiac output monitoring before and after passive leg raise (PLR). Hypothesis: PA Doppler and LVOT Doppler will have superior sensitivity and specificity to predict FRes in comparison to IVC-CI.
- The investigators will evaluate data acquisition duration and data acquisition failure rate of IVC-CI, PA Doppler, and LVOT Doppler. Hypothesis: PA Doppler will have shorter data acquisition durations in comparison to LVOT velocity variation and IVC-CI. Hypothesis: PA Doppler will have lower data acquisition failure rates in comparison to LVOT velocity variation and IVC-CI.
- The investigators will compare the ability of IVC-CI, PA Doppler, and LVOT Doppler to predict FRes in comparison to FRes as predicted by clinical judgment. Hypothesis: PA Doppler and LVOT Doppler will have superior sensitivity and specificity to predict FRes in comparison to clinical judgment.
- The investigators will evaluate the ability of dynamic changes in PA corrected flow times (cFT) to detect FRes relative to FRes as assessed by bioreactance cardiac output monitoring before and after PLR. Hypothesis: cFT will have greatest sensitivity and specificity to predict FRes at a Δflow time threshold of ≥15% after PLR.
Hypothesis: At a Δflow time threshold of ≥15%, cFT will have superior sensitivity and specificity to detect FRes in comparison to IVC-CI.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The investigators will recruit adult patients in the ED and ICU who are septic, have received an initial bolus of 20-30 cc/kg of IV fluid, and there is still a question by the clinical team of whether they are still fluid responsive.
Key inclusion criteria (7 listed)
- Subjects presenting to the ED will be screened in accordance with the Olive View Medical Center Sepsis Waiver, and subjects meeting two of the following four criteria will be eligible for inclusion in the study: Temperature >38/100.4 or <36/96.8, heart rate >90, respiratory rate >20 or PaCO2<32, and WBC >12K or <4K or > 10% bands (neutrophils). The clinical team will be contacted regarding patients identified based on this initial screening, and if the patient is determined to have a suspected infection and a fluid bolus is planned, the patient will be enrolled in the study if they meet the following criteria:
- Adult between the age of 18 to 90 years old;
- Not pregnant;
- Not using non-invasive positive pressure ventilation (CPAP or BiPAP);
- No history of heart, lung, and/or liver transplant;
Key exclusion criteria (8 listed)
- Pregnant;
- Using non-invasive positive pressure ventilation (CPAP or BiPAP);
- Presence of or suspected elevated intracranial pressure;
- Presence of central venous catheters or other medical devices that prevent the use of bedside ultrasound;
- History of heart, lung, and/or liver transplant;
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 |
|---|---|---|
| Ultrasound and NICOMAll patients enrolled will have all three ultrasound-based modalities for fluid responsiveness performed, as well as have NICOM data to serve as the comparison standard. | Device | – |
Primary outcome
Fluid responsiveness (measured as cardiac output change, velocity time integral change, or maximal velocity change of greater than 10%, with either passive leg raise maneuver or respiratory variability).
Time frame: Fluid responsiveness is assessed in a three minute interval using the study gold standard, the NICOM. FRes assessment using ultrasound will be performed during this time. One set of measurements will be obtained upon subject admission to the ED or ICU.
FRes is defined as the ability to predict that subjects who receive a small bolus of 250-500 ml of intravenous fluid will have a rise in their cardiac output or stroke volume of greater than 10%. FRes is a unit-less measurement, as it reflects the percent change in either stroke volume, cardiac index/output, IVC diameter, VTI, or Vmax, as a result of either a passive leg raise or the respiratory cycle. The criterion standard for FRes in this study will be assessed with the NICOM machine. Assessments of FRes using ultrasound-based measures (LVOT, carotid, femoral, and IVC) will be compared to the NICOM-determined assessment of FRes. Analysis is directed at how well the ultrasound-based definitions of FRes perform compared to the NICOM-based assessment.
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 8 Apr 2020.
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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. This study is not recruiting at the moment.
Alan Chiem, MD MPH principal investigator
Olive View-UCA
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 Sepsis and Fluid Overload, run by Olive View-UCLA Education & Research Institute at 1 site in United States.
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 7 inclusion and 8 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 8 Apr 2020. 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 United States. 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?
Fluid responsiveness (measured as cardiac output change, velocity time integral change, or maximal velocity change of greater than 10%, with either passive leg raise maneuver or respiratory variability). (time frame: Fluid responsiveness is assessed in a three minute interval using the study gold standard, the NICOM. FRes assessment using ultrasound will be performed during this time. One set of measurements will be obtained upon subject admission to the ED or ICU.). 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 8 Apr 2020.