Fluid ReponsivenessNCT03413657
Predicting Fluid Responsiveness Using Transiently Increased Intrathoracic Pressure in Mechanically Ventilated Patients
A study testing Increase in intrathoracic pressure in people with Fluid Reponsiveness, run by University of California, Davis at 1 site in United States.
Trial summary
The goal of this study is to identify in patients requiring active fluid resuscitation and mechanical ventilation for circulatory shock, can a controlled increase in intrathoracic pressure (either by positive-end expiratory pressure (PEEP) or tidal volume (TV)) predict responsiveness to additional fluid resuscitation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fluid Reponsiveness
- What is being tested?
- Increase in intrathoracic pressure
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Dec 2017to 13 Sep 2018
- Phase
- Interventional
- 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
Who may be able to join
- Mechanically ventilated
- Identified by treatment team as requiring intravenous fluid bolus
- Acute circulatory failure during admission (systolic blood pressure (SBP) ≤90 mmHg or mean arterial pressure (MAP) ≤70 mmHg or requiring vasopressors to maintain SBP >90 mmHg or MAP >70 mmHg, along with one or more of the following:
- urinary flow ≤0.5 mL/kg/min for ≥2 hours,
- heart rate ≥100 beats per minute
- presence of skin mottling
- blood lactate concentration ≥4 mmol/L
Who cannot join
- Contraindication to fluid bolus
- Assynchrony Index > 10%
- Clinically significant cardiac arrhythmia
- Severe valvular heart disease
- Chest tubes with air leak
- Abdominal compartment syndrome
Show all 12Show fewer
- Pregnancy
- Concurrent nebulized medication or inhaled nitric oxide
- Transthoracic echogenicity unsuitable for measuring velocity-time integral of aortic blood flow (SVI)
- Prisoner
- Clinical brain death
- PEEP > 15 cmH2O
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Davis
Sacramento, California, 95817
About this study
The goal of this study is to identify in patients requiring active fluid resuscitation and mechanical ventilation for circulatory shock, can a controlled increase in intrathoracic pressure (either by positive-end expiratory pressure (PEEP) or tidal volume (TV)) predict responsiveness to additional fluid resuscitation.
We hypothesize that a temporary, physiologically-safe increase in positive-end expiratory pressure (PEEP) and/or a temporary increase in tidal volume (from 6 cc/kg predicted body weight (PBW) to 8 cc/kg PBW) in patients requiring invasive mechanical ventilation will predict fluid responsiveness based upon an assessment of the change in pulse pressure and stroke volume variation.
Read the detailed description
Once an eligible subject is identified and written or telephone consent is obtained from the patient or surrogate as appropriate, we will record demographic data and clinical information including age, sex, height, actual body weight, predicted body weight (PBW), APACHE II on admission, primary diagnosis, reason for ICU admission, and dose of vasopressors.
Patients will be intubated and on assist-control volume ventilation receiving low tidal volumes. Sedation will be titrated per current MICU protocol to minimize patient discomfort and minimizing ventilator dyssynchrony. In keeping with standard practice, the dose of vasoactive medications will be kept constant during the intervention period. The standard practice is to titrate vasopressor therapy every five minutes, so keeping vasoactive medications constant for sixty seconds is in keeping with the standard of care. All subjects will be in an ICU setting and monitored per standard of care (vital signs, telemetry, ventilator data) by a respiratory therapist, pulmonary and critical care fellow or faculty member, and critical care nurse at the bedside throughout the entire intervention.
A point of care (POC) echocardiogram will be performed by the investigator performing the intervention in order to measure the stroke volume index (surrogate for cardiac output).
Subjects will be randomized to either undergo the PEEP challenge or tidal volume challenge first. After the initial challenge, subjects will cross over to whichever challenge has not yet been performed.
The simple changes to the ventilator we are proposing to use as challenges in this study are done frequently and routinely in the ICU with or without the supervision of a physician, but we will have a physician present throughout the entire proposed intervention. For the subjects undergoing PEEP challenge first, we will do the following:
- POC echocardiogram performed to measure SVI
- The tidal volume will be set to 6 mL/kg PBW and the patients will be monitored for 5 minutes for any variability in vital parameters. The subject's ventilatory parameters, vitals, hemodynamics, and oxygenation will be recorded on initial ventilator settings.
- PEEP challenge - PEEP will be increased by 50% for 60 seconds. The subject's ventilatory parameters, vitals, hemodynamics, and oxygenation will be recorded after 60 seconds.
- PEEP returned to initial settings.
- 2 minute washout period to prepare for tidal volume challenge.
- Tidal volume challenge - tidal volume raised to 8 cc/kg PBW for 60 seconds. The subject's ventilatory parameters, vitals, hemodynamics, and oxygenation will be recorded will be recorded after 60 seconds.
- Subjects ventilator settings returned to initial settings x 2 minutes.
- 500 cc crystalloid fluid bolus of the ICU team's choosing is then administered to the patient. The subject's ventilatory parameters, vitals, hemodynamics, and oxygenation will be measured.
- POC echocardiogram performed to measure SVI and determine if the subject is a fluid responder or non-responder.
The procedure for those randomized into the tidal volume challenge first will be similar, but the tidal volume challenge (e, above), rather than the PEEP challenge (b, above), will be performed first.
In the management of a critically ill patient in circulatory shock, physicians encounter the question of whether to administer fluid to the patient or not several times during the course of the patient's stay in the ICU. To ensure that our study is generalizable and applicable, we will perform the above protocol up to three times per subject. This is similar to previous studies using changes in intrathoracic pressure to predict fluid responsiveness. Additionally, we will have a larger number of interventions in order to better show a clear difference statistically.
- Conditions
- Fluid Reponsiveness
- Being tested
- Increase in intrathoracic pressure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Increase in intrathoracic pressureProcedure or surgery
Also called PEEP Challenge, Tidal Volume Challenge
Will transiently increase intrathoracic pressure for 60 seconds and monitor for changes in hemodynamics during this time.
| Study group | Role | What they receive |
|---|---|---|
| Fluid responders | Other | Patient's identified to have a significant increase in their cardiac output following a fluid bolus. Receives: Procedure: Increase in intrathoracic pressure |
| Fluid non-responders | Other | Patient's identified to NOT have a significant increase in their cardiac output following a fluid bolus. Receives: Procedure: Increase in intrathoracic pressure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulse Pressure Variation
Temporary increase in intrathoracic pressure (PEEP or TV) will predict fluid responsiveness using an absolute increase in pulse pressure variation by 3% or more.
Measured: Following 60 seconds of intrathoracic pressure challenge
Secondary outcomes (5)
Heart Rate
Temporary increase in intrathoracic pressure (PEEP or TV) will predict fluid responsiveness using an absolute decrease in heart rate by 15 beats per minute or more.
Measured: Following 60 seconds of intrathoracic pressure challenge
Mean Arterial Pressure
Temporary increase in intrathoracic pressure (PEEP or TV) will predict fluid responsiveness using an absolute decrease in MAP by 15 mmHg or more.
Measured: Following 60 seconds of intrathoracic pressure challenge
Mortality
Differences in 7 day mortality between fluid responders and non-responders
Measured: 7 days
Stroke Volume Variation
Temporary increase in intrathoracic pressure (PEEP or TV) will predict fluid responsiveness using an absolute increase in SVV of 4% or more.
Measured: Following 60 seconds of intrathoracic pressure challenge
End-tidal carbon dioxide
Temporary increase in intrathoracic pressure (PEEP or TV) will predict fluid responsiveness using an increase in EtCO2 by 4% or more.
Measured: Following 60 seconds of intrathoracic pressure challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2018
- Study start27 Dec 2017
- Primary completion13 Sep 2018
- Study completion13 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fluid ReponsivenessStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Subjects will be randomized to either undergo the PEEP challenge or tidal volume challenge first. After the initial challenge, subjects will cross over to whichever challenge has not yet been performed. Subjects will be separated into the following categories: "fluid responders" and "non-responders" and analyzed in those categories.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John Adams, MD, Principal investigator, Attending Physician
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03413657
- Sponsor's protocol ID
- 1086731
- Status last verified
- Jan 2020
- First submitted
- 11 Jan 2018
- Last updated
- 18 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Fluid Responsiveness Using Transiently Increased Intrathoracic Pressure in Mechanically Ventilated Patients
- ClinicalTrials.gov ID
- NCT03413657
- Acronym / sponsor ID
- 1086731
- Conditions
- Fluid Reponsiveness
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Study start
- 27 Dec 2017 (actual)
- Primary completion
- 13 Sep 2018 (actual)
- Study completion
- 13 Sep 2018 (actual)
- First posted
- 29 Jan 2018 (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 goal of this study is to identify in patients requiring active fluid resuscitation and mechanical ventilation for circulatory shock, can a controlled increase in intrathoracic pressure (either by positive-end expiratory pressure (PEEP) or tidal volume (TV)) predict responsiveness to additional fluid resuscitation.
We hypothesize that a temporary, physiologically-safe increase in positive-end expiratory pressure (PEEP) and/or a temporary increase in tidal volume (from 6 cc/kg predicted body weight (PBW) to 8 cc/kg PBW) in patients requiring invasive mechanical ventilation will predict fluid responsiveness based upon an assessment of the change in pulse pressure and stroke volume variation.
Detailed description
Once an eligible subject is identified and written or telephone consent is obtained from the patient or surrogate as appropriate, we will record demographic data and clinical information including age, sex, height, actual body weight, predicted body weight (PBW), APACHE II on admission, primary diagnosis, reason for ICU admission, and dose of vasopressors.
Patients will be intubated and on assist-control volume ventilation receiving low tidal volumes. Sedation will be titrated per current MICU protocol to minimize patient discomfort and minimizing ventilator dyssynchrony. In keeping with standard practice, the dose of vasoactive medications will be kept constant during the intervention period. The standard practice is to titrate vasopressor therapy every five minutes, so keeping vasoactive medications constant for sixty seconds is in keeping with the standard of care. All subjects will be in an ICU setting and monitored per standard of care (vital signs, telemetry, ventilator data) by a respiratory therapist, pulmonary and critical care fellow or faculty member, and critical care nurse at the bedside throughout the entire intervention.
A point of care (POC) echocardiogram will be performed by the investigator performing the intervention in order to measure the stroke volume index (surrogate for cardiac output).
Subjects will be randomized to either undergo the PEEP challenge or tidal volume challenge first. After the initial challenge, subjects will cross over to whichever challenge has not yet been performed.
The simple changes to the ventilator we are proposing to use as challenges in this study are done frequently and routinely in the ICU with or without the supervision of a physician, but we will have a physician present throughout the entire proposed intervention. For the subjects undergoing PEEP challenge first, we will do the following:
- POC echocardiogram performed to measure SVI
- The tidal volume will be set to 6 mL/kg PBW and the patients will be monitored for 5 minutes for any variability in vital parameters. The subject's ventilatory parameters, vitals, hemodynamics, and oxygenation will be recorded on initial ventilator settings.
- PEEP challenge - PEEP will be increased by 50% for 60 seconds. The subject's ventilatory parameters, vitals, hemodynamics, and oxygenation will be recorded after 60 seconds.
- PEEP returned to initial settings.
- 2 minute washout period to prepare for tidal volume challenge.
- Tidal volume challenge - tidal volume raised to 8 cc/kg PBW for 60 seconds. The subject's ventilatory parameters, vitals, hemodynamics, and oxygenation will be recorded will be recorded after 60 seconds.
- Subjects ventilator settings returned to initial settings x 2 minutes.
- 500 cc crystalloid fluid bolus of the ICU team's choosing is then administered to the patient. The subject's ventilatory parameters, vitals, hemodynamics, and oxygenation will be measured.
- POC echocardiogram performed to measure SVI and determine if the subject is a fluid responder or non-responder.
The procedure for those randomized into the tidal volume challenge first will be similar, but the tidal volume challenge (e, above), rather than the PEEP challenge (b, above), will be performed first.
In the management of a critically ill patient in circulatory shock, physicians encounter the question of whether to administer fluid to the patient or not several times during the course of the patient's stay in the ICU. To ensure that our study is generalizable and applicable, we will perform the above protocol up to three times per subject. This is similar to previous studies using changes in intrathoracic pressure to predict fluid responsiveness. Additionally, we will have a larger number of interventions in order to better show a clear difference statistically.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized to either undergo the PEEP challenge or tidal volume challenge first. After the initial challenge, subjects will cross over to whichever challenge has not yet been performed. Subjects will be separated into the following categories: "fluid responders" and "non-responders" and analyzed in those categories.
| Arm | Type | Receives |
|---|---|---|
| Fluid responders | Other | Procedure: Increase in intrathoracic pressurePatient's identified to have a significant increase in their cardiac output following a fluid bolus. |
| Fluid non-responders | Other | Procedure: Increase in intrathoracic pressurePatient's identified to NOT have a significant increase in their cardiac output following a fluid bolus. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Mechanically ventilated
- Identified by treatment team as requiring intravenous fluid bolus
- Acute circulatory failure during admission (systolic blood pressure (SBP) ≤90 mmHg or mean arterial pressure (MAP) ≤70 mmHg or requiring vasopressors to maintain SBP >90 mmHg or MAP >70 mmHg, along with one or more of the following:
- urinary flow ≤0.5 mL/kg/min for ≥2 hours,
- heart rate ≥100 beats per minute
Key exclusion criteria (12 listed)
- Contraindication to fluid bolus
- Assynchrony Index > 10%
- Clinically significant cardiac arrhythmia
- Severe valvular heart disease
- Chest tubes with air leak
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 |
|---|---|---|
| Increase in intrathoracic pressureAlso: PEEP Challenge, Tidal Volume ChallengeWill transiently increase intrathoracic pressure for 60 seconds and monitor for changes in hemodynamics during this time. | Procedure or surgery | Fluid non-responders, Fluid responders |
Primary outcome
Pulse Pressure Variation
Time frame: Following 60 seconds of intrathoracic pressure challenge
Temporary increase in intrathoracic pressure (PEEP or TV) will predict fluid responsiveness using an absolute increase in pulse pressure variation by 3% or more.
5 secondary outcomes
Heart Rate
Time frame: Following 60 seconds of intrathoracic pressure challenge
Mean Arterial Pressure
Time frame: Following 60 seconds of intrathoracic pressure challenge
Mortality
Time frame: 7 days
Stroke Volume Variation
Time frame: Following 60 seconds of intrathoracic pressure challenge
End-tidal carbon dioxide
Time frame: Following 60 seconds of intrathoracic pressure challenge
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 18 Jan 2020.
- Individual participant dataSharing planned: Undecided
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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.
John Adams, MD principal investigator
Attending Physician
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Increase in intrathoracic pressure in people with Fluid Reponsiveness, run by University of California, Davis 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 12 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 18 Jan 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?
Pulse Pressure Variation (time frame: Following 60 seconds of intrathoracic pressure challenge). 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 18 Jan 2020.