Circulatory FailurePhase 2/3EXHALENCT04037644
Volume Expansion With Albumin vs. Crystalloid and Expiratory Lung Impedance
A Phase 2/3 study testing Fluid loading with Albumin and Fluid loading with Ringer Lactate in people with Circulatory Failure, run by University of Milan at 1 site in Italy.
Trial summary
Acute circulatory failure reduces oxygen delivery below cellular requirements, potentially leading to organ failure. Intravenous fluids are generally administered with the aim of increasing cardiac output and restore organ perfusion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Circulatory Failure
- What is being tested?
- Fluid loading with Albumin and Fluid loading with Ringer Lactate
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteItaly
- Study dates
- 24 Jul 2019to 31 Dec 2020
- Phase
- Phase 2/3
- 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
- Patients >18 years with acute circulatory failure of any cause, receiving mechanical ventilation using volume-assisted control mode, without any spontaneous breathing activity, scheduled for a fluid bolus by their treating physician will be enrolled. Patients will only be included in the study once.
- Acute circulatory failure will be defined as the presence of a 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: 1) urinary flow ≤0.5 mL/kg/h for ≥2 hours, 2) heart rate ≥100 beats per minute, 3) presence of skin mottling, 4) blood lactate concentration ≥2 mmol/L, 5) oxygen saturation in the central venous blood <65%.
Who cannot join
- Patients having right ventricular dysfunction, anuria, pregnancy, presence of pneumothorax or lung emphysema, previous history of severe chronic obstructive pulmonary disease (GOLD III-IV) or contraindications to the use of EIT (e.g., presence of pacemaker or automatic implantable cardioverter-defibrillator) and impossibility to place the EIT belt in the right position (e.g., presence of surgical wounds dressing) will be excluded
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Ospedale San Paolo - Polo Universitario, ASST Santi Paolo e Carlo
Milan, MI, 20142
Davide Chiumello, Professor, +390281844020, chiumello@libero.it
Michele Umbrello, MD
About this study
Official title: Effect of Volume EXpansion witH ALbumin vs. Crystalloid on EIT-derived Expiratory Lung Impedance in Critically Ill, Hemodynamically Unstable Patients. A Single-blind, Randomized and Controlled Study
Acute circulatory failure reduces oxygen delivery below cellular requirements, potentially leading to organ failure. Intravenous fluids are generally administered with the aim of increasing cardiac output and restore organ perfusion. Nevertheless, only 50% of patients increase their cardiac output, while in the remainder not only does fluid loading provide no benefit but it also leads to volume overload (peripheral and pulmonary edema).
There are two types of resuscitation fluids, colloids and crystalloids. Given their oncotic pressure, colloids should remain in the intravascular space, while crystalloids distribute into the whole extracellular compartment, potentially increasing the risk of tissue edema. Surprisingly, only few studies directly compared albumin and crystalloids in terms of their overload-related side effects.
Read more
Electrical impedance tomography (EIT) is a noninvasive, radiation-free, lung imaging modality, which shows lung impedance as determined by small electrical currents. An increase in intrapulmonary gas volume increases impedance, while an increase in blood or fluid volume, lowers it. EIT has a high temporal resolution, allowing to assess ventilation and perfusion in real-time. Preliminary data suggest its value to assess the variations of intrathoracic fluid in patients with pulmonary edema.
The aim of the present single-blind, randomized, controlled study is to compare the effect of a fluid challenge with albumin vs. crystalloids on EIT-derived lung impedance in a group of 56 critically ill patients with acute circulatory failure. Our hypothesis is that fluid challenge with albumin leads to a lesser decrease in lung impedance, that is a lesser extravasation of fluids into the lungs.
Hemodynamic and respiratory variables, blood samples, cardiac ultrasound and EIT measurements will be recorded before the fluid challenge, and repeated at the end of fluid infusion, 20 and 60 minutes after. Factorial Analysis of variance for repeated measures will be used to assess the effects of fluid loading
- Conditions
- Circulatory Failure
- Being tested
- Fluid loading with Albumin, Fluid loading with Ringer Lactate
- Medical subject headings
- Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluid loading with AlbuminProcedure or surgery
Fluid loading with 200 ml of 4% Albumin to reverse acute circulatory failure
Fluid loading with Ringer LactateProcedure or surgery
Fluid loading with 5 ml per kg of actual body weight to reverse acute circulatory failure
| Study group | Role | What they receive |
|---|---|---|
| Albumin | Experimental | fluid loading with 200 mL of 4% albumin over a 10' interval Receives: Procedure: Fluid loading with Albumin |
| Ringer Lactate | Active comparator | fluid loading with 5 mL/kg actual body weight of Ringer Lactate over a 10' interval Receives: Procedure: Fluid loading with Ringer Lactate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in lung impedance
Reduction in EIT-derived end-expiratory lung impedance after the fluid challenge in the group of patients who will receive albumin as compared to patients who will receive crystalloids
Measured: Day 1
Secondary outcomes (2)
Comparison of the change expiratory lung impedance, as assessed by EIT, in fluid responders and non-responders
Comparison of the change in end-expiratory lung impedance, as assessed by EIT, after the fluid challenge with albumin or Ringer Lactate, in patient who will respond to the fluid challenge with an increase in their stroke volume, as compared to those who will not (non-responders)
Measured: Day 1
Effect of fluid loading with albumin or Ringer Lactate on the change in arterial blood oxygenation
Assesment of the reduction in oxygenation, as assessed by blood gas analysis, after the fluid challenge in the group of patients who will receive albumin as compared to patients who will receive crystalloids, and its relationship with the change in expiratory lung impedance, as assessed by EIT
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2019
- Study start24 Jul 2019
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2020 (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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Davide Chiumello, University of Milan
- Investigators
- Davide Chiumello, MD, Principal investigator, Ospedale San Paolo - Polo Universitario, ASST Santi Paolo e Carlo, Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04037644
- Sponsor's protocol ID
- EXHALE
- Acronym
- EXHALE
- Status last verified
- Jul 2019
- First submitted
- 24 Jul 2019
- Last updated
- 30 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Volume EXpansion witH ALbumin vs. Crystalloid on EIT-derived Expiratory Lung Impedance in Critically Ill, Hemodynamically Unstable Patients. A Single-blind, Randomized and Controlled Study
- ClinicalTrials.gov ID
- NCT04037644
- Acronym / sponsor ID
- EXHALE / EXHALE
- Conditions
- Circulatory Failure
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- 24 Jul 2019 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 30 Jul 2019 (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.
Acute circulatory failure reduces oxygen delivery below cellular requirements, potentially leading to organ failure. Intravenous fluids are generally administered with the aim of increasing cardiac output and restore organ perfusion. Nevertheless, only 50% of patients increase their cardiac output, while in the remainder not only does fluid loading provide no benefit but it also leads to volume overload (peripheral and pulmonary edema).
There are two types of resuscitation fluids, colloids and crystalloids. Given their oncotic pressure, colloids should remain in the intravascular space, while crystalloids distribute into the whole extracellular compartment, potentially increasing the risk of tissue edema. Surprisingly, only few studies directly compared albumin and crystalloids in terms of their overload-related side effects.
Electrical impedance tomography (EIT) is a noninvasive, radiation-free, lung imaging modality, which shows lung impedance as determined by small electrical currents. An increase in intrapulmonary gas volume increases impedance, while an increase in blood or fluid volume, lowers it. EIT has a high temporal resolution, allowing to assess ventilation and perfusion in real-time. Preliminary data suggest its value to assess the variations of intrathoracic fluid in patients with pulmonary edema.
The aim of the present single-blind, randomized, controlled study is to compare the effect of a fluid challenge with albumin vs. crystalloids on EIT-derived lung impedance in a group of 56 critically ill patients with acute circulatory failure. Our hypothesis is that fluid challenge with albumin leads to a lesser decrease in lung impedance, that is a lesser extravasation of fluids into the lungs.
Hemodynamic and respiratory variables, blood samples, cardiac ultrasound and EIT measurements will be recorded before the fluid challenge, and repeated at the end of fluid infusion, 20 and 60 minutes after. Factorial Analysis of variance for repeated measures will be used to assess the effects of fluid loading
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Albumin | Experimental | Procedure: Fluid loading with Albuminfluid loading with 200 mL of 4% albumin over a 10' interval |
| Ringer Lactate | Active comparator | Procedure: Fluid loading with Ringer Lactatefluid loading with 5 mL/kg actual body weight of Ringer Lactate over a 10' interval |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients >18 years with acute circulatory failure of any cause, receiving mechanical ventilation using volume-assisted control mode, without any spontaneous breathing activity, scheduled for a fluid bolus by their treating physician will be enrolled. Patients will only be included in the study once.
- Acute circulatory failure will be defined as the presence of a 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: 1) urinary flow ≤0.5 mL/kg/h for ≥2 hours, 2) heart rate ≥100 beats per minute, 3) presence of skin mottling, 4) blood lactate concentration ≥2 mmol/L, 5) oxygen saturation in the central venous blood <65%.
Key exclusion criteria (1 listed)
- Patients having right ventricular dysfunction, anuria, pregnancy, presence of pneumothorax or lung emphysema, previous history of severe chronic obstructive pulmonary disease (GOLD III-IV) or contraindications to the use of EIT (e.g., presence of pacemaker or automatic implantable cardioverter-defibrillator) and impossibility to place the EIT belt in the right position (e.g., presence of surgical wounds dressing) will be excluded
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 |
|---|---|---|
| Fluid loading with AlbuminFluid loading with 200 ml of 4% Albumin to reverse acute circulatory failure | Procedure or surgery | Albumin |
| Fluid loading with Ringer LactateFluid loading with 5 ml per kg of actual body weight to reverse acute circulatory failure | Procedure or surgery | Ringer Lactate |
Primary outcome
Change in lung impedance
Time frame: Day 1
Reduction in EIT-derived end-expiratory lung impedance after the fluid challenge in the group of patients who will receive albumin as compared to patients who will receive crystalloids
2 secondary outcomes
Comparison of the change expiratory lung impedance, as assessed by EIT, in fluid responders and non-responders
Time frame: Day 1
Effect of fluid loading with albumin or Ringer Lactate on the change in arterial blood oxygenation
Time frame: Day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Individual participant dataSharing planned: No
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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.
Davide Chiumello, MD principal investigator
Ospedale San Paolo - Polo Universitario, ASST Santi Paolo e Carlo, Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Fluid loading with Albumin and Fluid loading with Ringer Lactate in people with Circulatory Failure, run by University of Milan at 1 site in Italy.
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 2 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 30 Jul 2019. 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 Italy. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Davide Chiumello, MD (+390281844020, chiumello@libero.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in lung impedance (time frame: Day 1). 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 30 Jul 2019.