Acute Respiratory Distress SyndromeNCT02596178
Titration of PEEP During Mechanical Ventilation in Patients With ARDS Using Electrical Impedance Tomography.
A study testing Electrical Impedance Tomography in people with Acute Respiratory Distress Syndrome, run by Boston Children's Hospital at 1 site in United States.
Trial summary
Lung units that participate in gas exchange are known as 'recruited' lung. Patients with lung injury suffer from a proportion of units that do not participate in gas exchange (i.e. the derecruited lung), which results in impaired gas exchange and induces an inflammatory cascade. Read more about this study
- Who is it for?
- Ages 2 to 35 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- Electrical Impedance Tomography
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2016to 1 Jul 2020
- 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 2 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 1. All intubated and mechanically ventilated patients will be screened for the following inclusion criteria: 2. Age: Age 2 to 35 years 3. Arterial line 4. Have ARDS based on the following definition:
- The Berlin definition of ARDS36 i. Blood gas criteria:
- Mild: PaO2/FiO2 ratio of 201-300,
- Moderate: PaO2/FIO2 ratio of 101-200
- Severe: PaO2/FIO2 ratio of < 100 ii. Acute onset (within 1 week) of bilateral (patchy, diffuse, or homogeneous) infiltrates consistent with pulmonary edema on chest radiograph, and iii. No evidence of left atrial hypertension
- 5. Conventional lung protective mechanical ventilation Chest radiograph within the first 12h after the study recruitment
Who cannot join
- Meets the above criteria for ARDS for > 72 hours
- < 2 years of age or chest circumference < 55 cm.
- Clinically recognized airways disease (e.g. anatomic or reactive airway disease by history, treatment or flow graphics)
- Uncuffed endotracheal tube in place
- Airleak
- Congenital heart disease
Show all 23Show fewer
- Hemodynamically significant heart disease
- Congenital diaphragmatic hernia
- Pulmonary fibrosis
- Restrictive lung disease (other than ARDS)
- Cystic fibrosis
- Significant pulmonary hypertension requiring treatment (eg iNO, sildenafil, flolan)
- Severe brain injury with no intracranial pressure monitor or external ventricular drain in place
- Extra-corporeal life support
- Patients with unstable spinal injuries or diseases
- Body mass index > 50
- Active implant such as pacemaker, ICD, or diaphragm pacer
- Skin integrity issues in the area that the belt / electrodes will be placed, such as ulcers or open wounds
- Dressings or chest tubes that prohibit the placement of electrodes in the proper plain.
- Open chest
- Flail chest within the regional plain of the belt / electrodes
- If the medical team feels that the patient is not appropriate to enroll in the study based on medical, social or emotional concerns
- If the patient is too unstable to position the belt / electrodes and/or transition to the Draeger ventilator
Trial locations and contacts
1 site in 1 country.
United States1 site
Boston Children's Hospital
Boston, Massachusetts, 02115
About this study
Lung units that participate in gas exchange are known as 'recruited' lung. Patients with lung injury suffer from a proportion of units that do not participate in gas exchange (i.e. the derecruited lung), which results in impaired gas exchange and induces an inflammatory cascade. The level of PEEP is often coupled to indices of oxygenation such as PaO2, PaO2 to FIO2 ratio, or oxygen index. Currently, two strategies are widely accepted and considered equivocal, one strategy using a lower PEEP level coupled to a certain oxygen requirement, the other using a higher PEEP level.
The primary purpose of this study is to demonstrate the safety and efficacy of an electrical impedance tomography (EIT) PEEP titration protocol designed to recruit collapsed lung in children with ARDS and properly maintain lung volumes by setting an optimal PEEP level. A safety system has been developed using the ARDSnet FIO2/PEEP High (upper threshold limit) and Low (lower threshold limit) algorithm. Efficacy will be defined as an improvement in lung volume as assessed by electrical impedance tomography, lung compliance and by an improvement in markers of gas exchange. Safety will be defined as the incidence of barotrauma and hemodynamic consequences that occur during the protocol. Those results will be compared to incidences of barotrauma and hemodynamic compromise within the ARDS literature. Knowledge gained from this pilot will be instrumental in developing an EIT imagine guided protocol which will allow us to conduct future RCTs utilizing EIT technology
Read the detailed description
Currently, clinical practice regarding positive end expiratory pressure (PEEP) strategies for Acute Respiratory Distress Syndrome (ARDS) revolves around two PEEP/FIO2 algorithms developed NHLBI research ARDSnet program. These two algorithms are known as the "High" PEEP/ lower FIO2 and "Low" PEEP/ higher FIO2 protocols. The High PEEP/ lower FIO2 protocol is seen as aggressive or the highest PEEP level a clinician would want to set, while the low PEEP/ higher FIO2 is seen as lowest PEEP level a clinician would set. While many studies have demonstrated safety and efficacy of a PEEP setting based on a required fraction of inspired oxygen (FIO2) to maintain adequate oxygenation, yet there are equal outcomes between the two strategies. There is growing evidence that the Low PEEP/ higher FIO2 protocol leaves large proportions of the lung derecruited and the High PEEP/FIO2 protocol may create overdistension in the compliant sections of the lung that are largely free from disease as it uses a single gas exchange (oxygenation) parameter to determine PEEP settings.
Specific Aim 1: To demonstrate safety of an EIT guided PEEP titration strategy. (Hypothesis: EIT guided titration of PEEP will improve ventilation and oxygenation without increasing incidence of barotrauma or hemodynamic compromise.)
Specific Aim 2: To demonstrate the efficacy of a PEEP titration strategy to increase distribution of ventilation and improve oxygenation in children with ARDS utilizing an EIT guided protocol within two standards of care. (Hypothesis: EIT guided titration of PEEP will lead to a more homogeneous distribution of ventilation, improved lung compliance and improved ventilation and oxygenation.) Background and Significance Lung units participating in gas exchange are known as 'recruited' lung. Patients with lung injury suffer from a proportion of lung units which not participating in gas exchange (i.e. the derecruited state), at times resulting in impaired gas exchange. Derecruitment of alveoli may also cause intrapulmonary shunting and worsen lung injury through atelectotrauma. Outcomes in ARDS have improved significantly since clinicians have begun to employ lung protective strategies, including low-tidal volume ventilation and permissive hypercapnea. However, low-tidal volume ventilation has been recognized to decrease recruited lung volume, a phenomenon that persists despite the aggressive positive end-expiratory pressure (PEEP) strategy employed in ARDSNet studies. Atelectasis associated with low-tidal volume ventilation is relieved through the use of so-called sigh breaths, higher levels of PEEP or recruitment maneuverers. Further, the proportion of lung remaining in the derecruited state may contribute to the morbidity and mortality associated with ARDS. In adults, several strategies have been utilized to recruit the lung: sustained inflation (SI) and the maximal recruitment strategy. The so-called open lung approach (OLA) includes an SI followed by the setting of PEEP to the measured lower inflection point of the PV curve. An alternative approach to setting PEEP is a decremental PEEP titration, which includes the sequential lowering of PEEP until a predetermined decrement in PaO2 or SaO2 occurs.
The impact of lung recruitment in the long-term course of ARDS is not yet clear. It is clear that lung recruitment is most effective earlier in the course of ARDS. Grasso et al demonstrated that patients who received a recruitment maneuver on day 1±0.3 of ARDS could be recruited, versus patients recruited on day 7±1. Similarly, Gattinoni et al7 and Crotti et al found limited recruitment in patients who were well along in the course of ARDS. Borges et al, Tugrul et al, and Girgis et al all recruited patients early in the course of ARDS, and each found marked lung recruitment, on average, in all the patients studied. Each of these studied demonstrated an ability to improve oxygen saturations and (sometimes studied) end-expiratory lung volume. While no study has examined the effect of this change on morbidity or mortality, in children hypoxemia is known to be a common cause of morbidity. Importantly in children, treatment of hypoxia often drives escalating ventilator settings, the use of high frequency oscillatory ventilation (HFOV) or the use of extra-corporeal membrane oxygenation (ECMO). Early recruitment and proper titration of PEEP in children with ARDS may prevent the need for escalation of care towards these more invasive, and risk-imposing therapies.
Electrical Impedance Tomography (EIT) Barber and Brown introduced electrical impedance tomography to the medical community in the early 1980s. From there a wide spectrum of applications in medicine ranging from gastric emptying, brain function, breast imaging, to lung function have been explored. It is our belief that the most valuable benefit of EIT is in the monitoring of regional lung function in critically ill patients. Early EIT devices fell susceptible to poor sensitivity and signal interference in the clinical setting. After years and a renewed interest from a few commercial companies interested in ventilation technology, many of these shortcomings have been resolved. As with any new modality, EIT and its clinical utility and application need to be methodically explored; therefore we propose this IRB protocol to take us a step closer on this journey to develop a clinically useful tool.
Electrical impedance tomography capitalizes on changes in electrical impendence between air-filled versus tissue or fluid-filled spaces in order to characterize and quantify regional distribution of lung volume at the bedside. This technology has been validated in animal and human studies. The technology utilizes a series of 16 electrodes placed across the patient's chest. As small currents, which are undetectable to the subject, are passed between the electrodes, impedance is measured between and amongst the series. Through a complex interrogation and manipulation of these impedance values, a two-dimensional image is formed, and has been shown to correlate with clinical and radiographic changes in patients. The ability to estimate lung volume and regional distribution of gas non-invasively and in real time may give us insight as to what mode of ventilation or setting is more effective in optimizing positive pressure ventilation.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Electrical Impedance Tomography
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electrical Impedance TomographyDevice
Electrical impedance tomography capitalizes on changes in electrical impendence between air-filled versus tissue or fluid-filled spaces in order to characterize and quantify regional distribution of lung volume at the bedside.
| Study group | Role | What they receive |
|---|---|---|
| EIT Guided PEEP Therapy | Experimental | Not described Receives: Device: Electrical Impedance Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - measured by Barotrauma
Measured: 3 days
Safety - measured by Gas Exchange
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2015 (estimated)
- Study start1 Mar 2016
- Primary completion1 Dec 2019 (estimated)
- Study completion1 Jul 2020 (estimated)
Why it stopped: Research team no longer available.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Walsh, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02596178
- Sponsor's protocol ID
- IRB-P00017859
- Status last verified
- Jun 2019
- First submitted
- 2 Nov 2015
- Last updated
- 5 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Titration of PEEP During Mechanical Ventilation in Patients With ARDS Using Electrical Impedance Tomography.
- ClinicalTrials.gov ID
- NCT02596178
- Acronym / sponsor ID
- IRB-P00017859
- Conditions
- Acute Respiratory Distress Syndrome
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Research team no longer available.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- 1 Dec 2019 (estimated)
- Study completion
- 1 Jul 2020 (estimated)
- First posted
- 4 Nov 2015 (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.
Lung units that participate in gas exchange are known as 'recruited' lung. Patients with lung injury suffer from a proportion of units that do not participate in gas exchange (i.e. the derecruited lung), which results in impaired gas exchange and induces an inflammatory cascade. The level of PEEP is often coupled to indices of oxygenation such as PaO2, PaO2 to FIO2 ratio, or oxygen index. Currently, two strategies are widely accepted and considered equivocal, one strategy using a lower PEEP level coupled to a certain oxygen requirement, the other using a higher PEEP level.
The primary purpose of this study is to demonstrate the safety and efficacy of an electrical impedance tomography (EIT) PEEP titration protocol designed to recruit collapsed lung in children with ARDS and properly maintain lung volumes by setting an optimal PEEP level. A safety system has been developed using the ARDSnet FIO2/PEEP High (upper threshold limit) and Low (lower threshold limit) algorithm. Efficacy will be defined as an improvement in lung volume as assessed by electrical impedance tomography, lung compliance and by an improvement in markers of gas exchange. Safety will be defined as the incidence of barotrauma and hemodynamic consequences that occur during the protocol. Those results will be compared to incidences of barotrauma and hemodynamic compromise within the ARDS literature. Knowledge gained from this pilot will be instrumental in developing an EIT imagine guided protocol which will allow us to conduct future RCTs utilizing EIT technology
Detailed description
Currently, clinical practice regarding positive end expiratory pressure (PEEP) strategies for Acute Respiratory Distress Syndrome (ARDS) revolves around two PEEP/FIO2 algorithms developed NHLBI research ARDSnet program. These two algorithms are known as the "High" PEEP/ lower FIO2 and "Low" PEEP/ higher FIO2 protocols. The High PEEP/ lower FIO2 protocol is seen as aggressive or the highest PEEP level a clinician would want to set, while the low PEEP/ higher FIO2 is seen as lowest PEEP level a clinician would set. While many studies have demonstrated safety and efficacy of a PEEP setting based on a required fraction of inspired oxygen (FIO2) to maintain adequate oxygenation, yet there are equal outcomes between the two strategies. There is growing evidence that the Low PEEP/ higher FIO2 protocol leaves large proportions of the lung derecruited and the High PEEP/FIO2 protocol may create overdistension in the compliant sections of the lung that are largely free from disease as it uses a single gas exchange (oxygenation) parameter to determine PEEP settings.
Specific Aim 1: To demonstrate safety of an EIT guided PEEP titration strategy. (Hypothesis: EIT guided titration of PEEP will improve ventilation and oxygenation without increasing incidence of barotrauma or hemodynamic compromise.)
Specific Aim 2: To demonstrate the efficacy of a PEEP titration strategy to increase distribution of ventilation and improve oxygenation in children with ARDS utilizing an EIT guided protocol within two standards of care. (Hypothesis: EIT guided titration of PEEP will lead to a more homogeneous distribution of ventilation, improved lung compliance and improved ventilation and oxygenation.) Background and Significance Lung units participating in gas exchange are known as 'recruited' lung. Patients with lung injury suffer from a proportion of lung units which not participating in gas exchange (i.e. the derecruited state), at times resulting in impaired gas exchange. Derecruitment of alveoli may also cause intrapulmonary shunting and worsen lung injury through atelectotrauma. Outcomes in ARDS have improved significantly since clinicians have begun to employ lung protective strategies, including low-tidal volume ventilation and permissive hypercapnea. However, low-tidal volume ventilation has been recognized to decrease recruited lung volume, a phenomenon that persists despite the aggressive positive end-expiratory pressure (PEEP) strategy employed in ARDSNet studies. Atelectasis associated with low-tidal volume ventilation is relieved through the use of so-called sigh breaths, higher levels of PEEP or recruitment maneuverers. Further, the proportion of lung remaining in the derecruited state may contribute to the morbidity and mortality associated with ARDS. In adults, several strategies have been utilized to recruit the lung: sustained inflation (SI) and the maximal recruitment strategy. The so-called open lung approach (OLA) includes an SI followed by the setting of PEEP to the measured lower inflection point of the PV curve. An alternative approach to setting PEEP is a decremental PEEP titration, which includes the sequential lowering of PEEP until a predetermined decrement in PaO2 or SaO2 occurs.
The impact of lung recruitment in the long-term course of ARDS is not yet clear. It is clear that lung recruitment is most effective earlier in the course of ARDS. Grasso et al demonstrated that patients who received a recruitment maneuver on day 1±0.3 of ARDS could be recruited, versus patients recruited on day 7±1. Similarly, Gattinoni et al7 and Crotti et al found limited recruitment in patients who were well along in the course of ARDS. Borges et al, Tugrul et al, and Girgis et al all recruited patients early in the course of ARDS, and each found marked lung recruitment, on average, in all the patients studied. Each of these studied demonstrated an ability to improve oxygen saturations and (sometimes studied) end-expiratory lung volume. While no study has examined the effect of this change on morbidity or mortality, in children hypoxemia is known to be a common cause of morbidity. Importantly in children, treatment of hypoxia often drives escalating ventilator settings, the use of high frequency oscillatory ventilation (HFOV) or the use of extra-corporeal membrane oxygenation (ECMO). Early recruitment and proper titration of PEEP in children with ARDS may prevent the need for escalation of care towards these more invasive, and risk-imposing therapies.
Electrical Impedance Tomography (EIT) Barber and Brown introduced electrical impedance tomography to the medical community in the early 1980s. From there a wide spectrum of applications in medicine ranging from gastric emptying, brain function, breast imaging, to lung function have been explored. It is our belief that the most valuable benefit of EIT is in the monitoring of regional lung function in critically ill patients. Early EIT devices fell susceptible to poor sensitivity and signal interference in the clinical setting. After years and a renewed interest from a few commercial companies interested in ventilation technology, many of these shortcomings have been resolved. As with any new modality, EIT and its clinical utility and application need to be methodically explored; therefore we propose this IRB protocol to take us a step closer on this journey to develop a clinically useful tool.
Electrical impedance tomography capitalizes on changes in electrical impendence between air-filled versus tissue or fluid-filled spaces in order to characterize and quantify regional distribution of lung volume at the bedside. This technology has been validated in animal and human studies. The technology utilizes a series of 16 electrodes placed across the patient's chest. As small currents, which are undetectable to the subject, are passed between the electrodes, impedance is measured between and amongst the series. Through a complex interrogation and manipulation of these impedance values, a two-dimensional image is formed, and has been shown to correlate with clinical and radiographic changes in patients. The ability to estimate lung volume and regional distribution of gas non-invasively and in real time may give us insight as to what mode of ventilation or setting is more effective in optimizing positive pressure ventilation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EIT Guided PEEP Therapy | Experimental | Device: Electrical Impedance Tomography |
Who may qualify
- Ages
- 2 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 1. All intubated and mechanically ventilated patients will be screened for the following inclusion criteria: 2. Age: Age 2 to 35 years 3. Arterial line 4. Have ARDS based on the following definition:
- The Berlin definition of ARDS36 i. Blood gas criteria:
- Mild: PaO2/FiO2 ratio of 201-300,
- Moderate: PaO2/FIO2 ratio of 101-200
- Severe: PaO2/FIO2 ratio of < 100 ii. Acute onset (within 1 week) of bilateral (patchy, diffuse, or homogeneous) infiltrates consistent with pulmonary edema on chest radiograph, and iii. No evidence of left atrial hypertension
Key exclusion criteria (23 listed)
- Meets the above criteria for ARDS for > 72 hours
- < 2 years of age or chest circumference < 55 cm.
- Clinically recognized airways disease (e.g. anatomic or reactive airway disease by history, treatment or flow graphics)
- Uncuffed endotracheal tube in place
- Airleak
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 |
|---|---|---|
| Electrical Impedance TomographyElectrical impedance tomography capitalizes on changes in electrical impendence between air-filled versus tissue or fluid-filled spaces in order to characterize and quantify regional distribution of lung volume at the bedside. | Device | EIT Guided PEEP Therapy |
Primary outcome
Safety - measured by Barotrauma
Time frame: 3 days
Safety - measured by Gas Exchange
Time frame: 3 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2019.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Electrical Impedance Tomography in people with Acute Respiratory Distress Syndrome, run by Boston Children's Hospital 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 6 inclusion and 23 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: withdrawn, as of the sponsor's last update on 5 Jun 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 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 was withdrawn before enrolling participants, so there are no results.
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?
Safety - measured by Barotrauma (time frame: 3 days). The study lists 2 primary outcomes in all. 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 5 Jun 2019.