ARDS (Acute Respiratory Distress Syndrome)PROTECT-ARDSNCT07790133
Trial of Total Lung Protective Ventilation in Adult VV-ECMO Patients With Severe ARDS
A study testing Mechanical Power Targeted Ventilation in people with ARDS (Acute Respiratory Distress Syndrome) and VV ECMO, run by University of Virginia at 1 site in United States.
Trial summary
The purpose of this study is to find a better way to protect the lungs of patients with Acute Respiratory Distress Syndrome (ARDS) who are being treated with a mechanical ventilator in addition to an extracorporeal membrane oxygenation (ECMO) machine. ARDS is a serious lung condition that makes it hard to breathe. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ARDS (Acute Respiratory Distress Syndrome), VV ECMO
- What is being tested?
- Mechanical Power Targeted Ventilation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2026to 31 Dec 2028
- Phase
- Interventional
- 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
Who may be able to join
- On VV ECMO for less than 24 hours at time of study consent
- Severe ARDS as the primary etiology of respiratory failure defined by:
- Acute onset: Within 1 week of known clinical insult
- Bilateral infiltrates: Evidence of fluid/inflammation in both lungs on X-ray, CT, or US, not fully explained by cardiac failure or fluid overload
- Origin of Edema: Respiratory failure not fully explained by cardiac failure or fluid overload
- Oxygenation impairment (Severe): PaO2/FiO2 ≤ 100 mm HG (Partial pressure of arterial oxygen/Fraction of inspired oxygen)
- Age 18 or greater
Who cannot join
- Have received ECMO for >24 hours
- Are on VV ECMO but are not mechanically ventilated, or are planned not to have/not require invasive mechanical ventilation for >24 hours
- Patient is pregnant
- Patient is a prisoner
- Receiving VV ECMO as a bridge to transplant or history of lung transplant
- History of pneumectomy or lobectomy
- Age < 18
- Are on any hybrid configuration of ECMO including an arterial limb (i.e., VAV, VVA, VA, etc.)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Virginia
Charlottesville, Virginia, 22903
Department of Anesthesiology, (434) 924-9508, ZNN7YF@uvahealth.org
Jenny Phillips, RN, CCRC, 434-297-8136, JVP8A@uvahealth.org
About this study
Official title: Pilot Trial Evaluating a Mechanical Power Targeted Ventilation Strategy in Adult VV ECMO Patients With Severe ARDS
The purpose of this study is to find a better way to protect the lungs of patients with Acute Respiratory Distress Syndrome (ARDS) who are being treated with a mechanical ventilator in addition to an extracorporeal membrane oxygenation (ECMO) machine. ARDS is a serious lung condition that makes it hard to breathe. People with ARDS often need care in the intensive care unit (ICU) and can become very sick with high mortality rates despite optimal care.
Doctors usually support patients with through ARDS with a breathing machine called a ventilator. The ventilator helps lungs imitate taking small breaths to help protect the lungs from more damage, however ventilator induced lung injury (VILI) can still contribute significantly to organ injury.
For patients in whom a ventilator is not enough support due to the severity of their lung disease, veno-venous (VV) ECMO can fully support the lungs while they recover. In these sickest patients, it is important to avoid causing more lung damage with the ventilator. Protecting the lungs may help them heal faster and may also help protect other parts of the body. More people are now being treated with VV ECMO, but there is still not enough research to know which ventilator settings are safest and work best. Most current recommendations are based on doctors' experience instead of research studies. This study will help researchers learn the best way to use ventilators for patients on VV ECMO and improve their recovery.
Read the detailed description
Acute respiratory distress syndrome (ARDS) is a common intensive care unit (ICU) admission diagnosis with mortality nearing 50% in severe cases. Traditional management focuses on lung protective ventilation consisting of low tidal volumes while limiting plateau and driving pressures. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a guideline recommended intervention for patients with severe ARDS refractory to other interventions. The optimal lung protective ventilation strategy for patients supported by VV-ECMO is unknown.
Over the past few decades, significant effort in the form of multiple international, multicenter, randomized controlled trials have evaluated lung protective ventilation strategies in ARDS, highlighted by the ARMA trial which showed an 8.8% absolute mortality reduction with low tidal volume ventilation and limiting plateau pressure to <30 cmH2O compared to standard of care at the time. These trials have helped define lung protective ventilation parameters over the past few decades, leading to significant improvements in mortality over that time. For patients with respiratory failure refractory enough to require VV ECMO support, avoiding further ventilator induced lung injury (VILI) is paramount to optimize the chances of lung recovery and avoid extrapulmonary organ dysfunction. However, despite the rapid increase in the utilization of VV ECMO for severe respiratory failure, very little prospective or randomized research has attempted to evaluate what constitutes lung protective ventilation in this patient population. In the absence of any current randomized trial evidence, management guidelines rely on expert opinion alone. These guidelines are extrapolated from lung protective ventilation studied in patients undergoing conventional mechanical ventilation despite significant differences introduced by the presence of the ECMO circuit, most notably the ability of the circuit to assume most if not all of the pulmonary support while enabling ultra-low tidal volume "lung rest" ventilation with tidal volumes of 3-4 cc/kg predicted body weight (PBW), limiting plateau pressures to ≤ 24 cmH2O but no greater than 30 cmH2O, and maintaining a respiratory rate of 4-15 breaths/minute but no greater than 30. Notably, the largest prospective observational trial of patients supported by VV ECMO for respiratory failure did not suggest an outcome benefit for any of these single traditionally targeted ventilator variables. Given the increasing utilization of VV ECMO for ARDS, there is a need for prospective evaluation of a more comprehensive approach to ventilator management as a means to minimize VILI and improve outcomes in this critically ill patient population.
Mechanical power (MP) attempts to more comprehensively unify all ventilator-related causes of lung injury such as distending pressure, tidal volume, flow, and respiratory rate into a single, quantifiable variable. Thus, MP is an innovative approach to more comprehensively reducing VILI compared to traditional tidal volume or plateau targets, providing a potential new benchmark for enhanced lung-protective ventilation. MP has been independently associated with poor patient outcomes even with low tidal volume and driving pressure in multiple studies in patients with and without ARDS, as well as ECMO and non-ECMO supported patient populations across numerous retrospective and observational studies. However, despite this strong correlation, the feasibility of prospectively evaluating a MP-based strategy in a randomized fashion remains unknown. The aim of this trial is to evaluate the feasibility, safety, and tolerability of a MP-targeted ventilation protocol in patients with severe ARDS requiring VV ECMO support as the first step in ultimately evaluating the ability of such a strategy to directly impact and improve patient-oriented outcomes.
Description of Study Intervention:
After randomization, patients will subsequently be assigned to either a low mechanical power target (2-4 J/min) or usual care. This range was chosen as it closely mirrors the power of normal breathing in healthy subjects and falls on the lower range of that reported in retrospective and observational trials, indicating potential feasibility. As a part of the protocol, patients in both arms will meet the current standard of care regarding the individual parameters of ultra-lung protective ventilation and "lung rest" while on VV-ECMO as it is currently defined. The low mechanical power target arm will follow a well-defined mechanical ventilator management algorithm to meet the assigned target, as described below. Patients in the usual care arm will be managed at the discretion of the treating intensivist with care, including mechanical ventilation settings, sedation, VV ECMO, and additional adjunct therapies, reflecting current best practice guidelines.
For patients assigned to the intervention arm, the patient will be placed on volume control (VC) or pressure control (PC) ventilation with either an initial tidal volume of 3-4cc/kg predicted body weight (PBW) (for VC) or inspiratory pressure required to reach the same tidal volume goal (for PC), FiO2 set between 0.30-0.50, and a PEEP of at least 10. This tidal volume or inspiratory pressure, for VC and PC ventilation respectively, will then be titrated down to meet a goal plateau pressure of less than or equal to 24 cmH2O, and a target driving pressure no greater than 14 cmH2O. Finally, the respiratory rate will then be titrated between 1 and 15 to meet the specified mechanical power goal range. Once the respiratory rate has been lowered to 8, tidal volumes (or inspiratory pressure required to meet this goal) will be lowered to 3cc/kg PBW prior to further reductions in respiratory rate. MP will be calculated every two hours and adjusted as needed to stay within the goal MP range until pre-specified weaning criteria are met.
- Being tested
- Mechanical Power Targeted Ventilation
- Keywords
- ARDS, VV ECMO, Mechanical Power, Ventilator Induced Lung Injury
- Medical subject headings
- Acute Lung Injury, Ventilator-Induced Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mechanical Power Targeted VentilationProcedure or surgery
For patients assigned to the intervention arm, the patient will be placed on volume control (VC) or pressure control (PC) ventilation with either an initial tidal volume of 3-4cc/kg predicted body weight (PBW) (for VC) or inspiratory pressure required to reach the same tidal volume goal (for PC), FiO2 set between 0.30-0.50, and PEEP of at least 10. This tidal volume or inspiratory pressure, for VC and PC respectively, will then be titrated down to meet a goal plateau pressure of less than or equal to 24 cmH2O, and a target driving pressure no greater than 14 cmH2O. Finally, the respiratory rate will then be titrated between 1 and 15 to meet the specified mechanical power goal range. Once the respiratory rate has been lowered to 8, tidal volumes will be lowered to 3cc/kg PBW prior to further reductions in respiratory rate. Mechanical power (MP) will be calculated every two hours and adjusted as needed to stay within the goal MP range until pre-defined weaning criteria are met.
| Study group | Role | What they receive |
|---|---|---|
| Routine Care | No intervention | This arm will receive routine care for all aspects of care including ECMO and mechanical ventilation as decided by the attending physician. |
| Targeted Intervention | Experimental | This group will have their mechanical ventilator settings adjusted by the study team to a target mechanical power of between 2-4 J/minute, closely mimicking the mechanical power of that required for healthy adult breathing. The adjustments will be made using the mechanical power ventilation formula with information specific to the person, titrating each of the variables historically associated with ventilator induced lung injury in tandem. The ventilator will be monitored and adjusted as needed every 2 hours for 7 days while patients are on ECMO. Receives: Procedure: Mechanical Power Targeted Ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of prospective, randomized mechanical power-based strategy to establish a causal relationship between MP and clinical outcomes.
The primary outcome is to assess the feasibility of the intervention protocol, as assessed by the number of patients adhering to mechanical power (MP) protocol, with a target adherence of >/= 90% of the intervention time spent within the assigned mechanical power range.
Measured: From enrollment to the end of the intervention window of 7 days.
Secondary outcomes (3)
To evaluate the safety of a total lung protective ventilation strategy utilizing a mechanical power targeted strategy versus conventional ultra-low tidal volume ventilation.
Secondary outcome one: safety, as measured by the incidence of refractory hypoxemia and/or hypercarbia occurring during intervention window as defined by a sustained PaO2 of <50 mmHg or saturation <85% on two arterial blood gases drawn >30 minutes apart and for hypercarbia as sustained PaCO2 >65 mmHg with associated respiratory acidosis noted by a pH < 7.20 on two arterial blood gases drawn >30 minutes apart. Reported as number of patients in whom either incidence occurred at least one time during intervention window.
Measured: From enrollment to end of intervention window of 7 days
To evaluate the tolerability of a total lung protective ventilation strategy utilizing a mechanical power targeted strategy versus conventional ultra-low tidal volume ventilation.
Second outcome measure: Tolerability; as measured by sedative requirements as assessed by daily the Richmond Agitation-Sedation Scale (RASS) ranging from -5 to +4 with lower scores indicating a need for deeper sedation and less tolerability. Reported as median numerical score with interquartile range (IQR).
Measured: From enrollment to end of intervention window of 7 days
To evaluate the tolerability of a total lung protective ventilation strategy utilizing a mechanical power targeted strategy versus conventional ultra-low tidal volume ventilation.
Second outcome measure: Tolerability; as measured by requirement for use of continuous neuromuscular blockade. Reported as median number of days with interquartile ranges for which a patient requires continuous neuromuscular blockade for greater than four hours. A lower median number of days receiving continuous neuromuscular blockade indicates greater tolerability.
Measured: From enrollment to end of intervention window of 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2026
- Study start1 Sep 2026 (estimated)
- Primary completion30 Sep 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for ARDS (Acute Respiratory Distress Syndrome)Studies of the same condition, open and under way.
- More trials run by University of VirginiaThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ryan Lee, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07790133
- Sponsor's protocol ID
- HSR 303640
- Other IDs
- FP00429174
- Acronym
- PROTECT-ARDS
- Status last verified
- Aug 2026
- First submitted
- 13 Aug 2026
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All de-identified IPD that underlie results in a publication.
Publications
van der Zee P, Rietdijk W, Somhorst P, Endeman H, Gommers D. A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality. Crit Care. 2020 May 24;24(1):243. doi: 10.1186/s13054-020-02913-7.
PubMed 32448370Tonna JE, Peltan I, Brown SM, Herrick JS, Keenan HT; University of Utah Mechanical Power Study Group. Mechanical power and driving pressure as predictors of mortality among patients with ARDS. Intensive Care Med. 2020 Oct;46(10):1941-1943. doi: 10.1007/s00134-020-06130-2. Epub 2020 Jun 5. No abstract available.
PubMed 32504104von During S, Liu K, Munshi L, Kim SJ, Urner M, Adhikari NKJ, Parhar KKS, Fan E. The Association Between Mechanical Power Within the First 24 Hours and ICU Mortality in Mechanically Ventilated Adult Patients With Acute Hypoxemic Respiratory Failure: A Registry-Based Cohort Study. Chest. 2025 Oct;168(4):901-911. doi: 10.1016/j.chest.2025.03.012. Epub 2025 Mar 28.
PubMed 40158848von During S, Parhar KKS, Adhikari NKJ, Urner M, Kim SJ, Munshi L, Liu K, Fan E. Understanding ventilator-induced lung injury: The role of mechanical power. J Crit Care. 2025 Feb;85:154902. doi: 10.1016/j.jcrc.2024.154902. Epub 2024 Sep 5.
PubMed 39241350Serpa Neto A, Deliberato RO, Johnson AEW, Bos LD, Amorim P, Pereira SM, Cazati DC, Cordioli RL, Correa TD, Pollard TJ, Schettino GPP, Timenetsky KT, Celi LA, Pelosi P, Gama de Abreu M, Schultz MJ; PROVE Network Investigators. Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts. Intensive Care Med. 2018 Nov;44(11):1914-1922. doi: 10.1007/s00134-018-5375-6. Epub 2018 Oct 5.
PubMed 30291378Gattinoni L, Tonetti T, Cressoni M, Cadringher P, Herrmann P, Moerer O, Protti A, Gotti M, Chiurazzi C, Carlesso E, Chiumello D, Quintel M. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016 Oct;42(10):1567-1575. doi: 10.1007/s00134-016-4505-2. Epub 2016 Sep 12.
PubMed 27620287Schmidt M, Pham T, Arcadipane A, Agerstrand C, Ohshimo S, Pellegrino V, Vuylsteke A, Guervilly C, McGuinness S, Pierard S, Breeding J, Stewart C, Ching SSW, Camuso JM, Stephens RS, King B, Herr D, Schultz MJ, Neuville M, Zogheib E, Mira JP, Roze H, Pierrot M, Tobin A, Hodgson C, Chevret S, Brodie D, Combes A. Mechanical Ventilation Management during Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome. An International Multicenter Prospective Cohort. Am J Respir Crit Care Med. 2019 Oct 15;200(8):1002-1012. doi: 10.1164/rccm.201806-1094OC.
PubMed 31144997Tonna JE, Abrams D, Brodie D, Greenwood JC, Rubio Mateo-Sidron JA, Usman A, Fan E. Management of Adult Patients Supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO J. 2021 Jun 1;67(6):601-610. doi: 10.1097/MAT.0000000000001432.
PubMed 33965970Qadir N, Sahetya S, Munshi L, Summers C, Abrams D, Beitler J, Bellani G, Brower RG, Burry L, Chen JT, Hodgson C, Hough CL, Lamontagne F, Law A, Papazian L, Pham T, Rubin E, Siuba M, Telias I, Patolia S, Chaudhuri D, Walkey A, Rochwerg B, Fan E. An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2024 Jan 1;209(1):24-36. doi: 10.1164/rccm.202311-2011ST.
PubMed 38032683Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
PubMed 26903337
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Trial Evaluating a Mechanical Power Targeted Ventilation Strategy in Adult VV ECMO Patients With Severe ARDS
- ClinicalTrials.gov ID
- NCT07790133
- Acronym / sponsor ID
- PROTECT-ARDS / HSR 303640
- Keywords
- ARDS, VV ECMO, Mechanical Power, Ventilator Induced Lung Injury
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 27 Aug 2026 (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 purpose of this study is to find a better way to protect the lungs of patients with Acute Respiratory Distress Syndrome (ARDS) who are being treated with a mechanical ventilator in addition to an extracorporeal membrane oxygenation (ECMO) machine. ARDS is a serious lung condition that makes it hard to breathe. People with ARDS often need care in the intensive care unit (ICU) and can become very sick with high mortality rates despite optimal care.
Doctors usually support patients with through ARDS with a breathing machine called a ventilator. The ventilator helps lungs imitate taking small breaths to help protect the lungs from more damage, however ventilator induced lung injury (VILI) can still contribute significantly to organ injury.
For patients in whom a ventilator is not enough support due to the severity of their lung disease, veno-venous (VV) ECMO can fully support the lungs while they recover. In these sickest patients, it is important to avoid causing more lung damage with the ventilator. Protecting the lungs may help them heal faster and may also help protect other parts of the body. More people are now being treated with VV ECMO, but there is still not enough research to know which ventilator settings are safest and work best. Most current recommendations are based on doctors' experience instead of research studies. This study will help researchers learn the best way to use ventilators for patients on VV ECMO and improve their recovery.
Detailed description
Acute respiratory distress syndrome (ARDS) is a common intensive care unit (ICU) admission diagnosis with mortality nearing 50% in severe cases. Traditional management focuses on lung protective ventilation consisting of low tidal volumes while limiting plateau and driving pressures. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a guideline recommended intervention for patients with severe ARDS refractory to other interventions. The optimal lung protective ventilation strategy for patients supported by VV-ECMO is unknown.
Over the past few decades, significant effort in the form of multiple international, multicenter, randomized controlled trials have evaluated lung protective ventilation strategies in ARDS, highlighted by the ARMA trial which showed an 8.8% absolute mortality reduction with low tidal volume ventilation and limiting plateau pressure to <30 cmH2O compared to standard of care at the time. These trials have helped define lung protective ventilation parameters over the past few decades, leading to significant improvements in mortality over that time. For patients with respiratory failure refractory enough to require VV ECMO support, avoiding further ventilator induced lung injury (VILI) is paramount to optimize the chances of lung recovery and avoid extrapulmonary organ dysfunction. However, despite the rapid increase in the utilization of VV ECMO for severe respiratory failure, very little prospective or randomized research has attempted to evaluate what constitutes lung protective ventilation in this patient population. In the absence of any current randomized trial evidence, management guidelines rely on expert opinion alone. These guidelines are extrapolated from lung protective ventilation studied in patients undergoing conventional mechanical ventilation despite significant differences introduced by the presence of the ECMO circuit, most notably the ability of the circuit to assume most if not all of the pulmonary support while enabling ultra-low tidal volume "lung rest" ventilation with tidal volumes of 3-4 cc/kg predicted body weight (PBW), limiting plateau pressures to ≤ 24 cmH2O but no greater than 30 cmH2O, and maintaining a respiratory rate of 4-15 breaths/minute but no greater than 30. Notably, the largest prospective observational trial of patients supported by VV ECMO for respiratory failure did not suggest an outcome benefit for any of these single traditionally targeted ventilator variables. Given the increasing utilization of VV ECMO for ARDS, there is a need for prospective evaluation of a more comprehensive approach to ventilator management as a means to minimize VILI and improve outcomes in this critically ill patient population.
Mechanical power (MP) attempts to more comprehensively unify all ventilator-related causes of lung injury such as distending pressure, tidal volume, flow, and respiratory rate into a single, quantifiable variable. Thus, MP is an innovative approach to more comprehensively reducing VILI compared to traditional tidal volume or plateau targets, providing a potential new benchmark for enhanced lung-protective ventilation. MP has been independently associated with poor patient outcomes even with low tidal volume and driving pressure in multiple studies in patients with and without ARDS, as well as ECMO and non-ECMO supported patient populations across numerous retrospective and observational studies. However, despite this strong correlation, the feasibility of prospectively evaluating a MP-based strategy in a randomized fashion remains unknown. The aim of this trial is to evaluate the feasibility, safety, and tolerability of a MP-targeted ventilation protocol in patients with severe ARDS requiring VV ECMO support as the first step in ultimately evaluating the ability of such a strategy to directly impact and improve patient-oriented outcomes.
Description of Study Intervention:
After randomization, patients will subsequently be assigned to either a low mechanical power target (2-4 J/min) or usual care. This range was chosen as it closely mirrors the power of normal breathing in healthy subjects and falls on the lower range of that reported in retrospective and observational trials, indicating potential feasibility. As a part of the protocol, patients in both arms will meet the current standard of care regarding the individual parameters of ultra-lung protective ventilation and "lung rest" while on VV-ECMO as it is currently defined. The low mechanical power target arm will follow a well-defined mechanical ventilator management algorithm to meet the assigned target, as described below. Patients in the usual care arm will be managed at the discretion of the treating intensivist with care, including mechanical ventilation settings, sedation, VV ECMO, and additional adjunct therapies, reflecting current best practice guidelines.
For patients assigned to the intervention arm, the patient will be placed on volume control (VC) or pressure control (PC) ventilation with either an initial tidal volume of 3-4cc/kg predicted body weight (PBW) (for VC) or inspiratory pressure required to reach the same tidal volume goal (for PC), FiO2 set between 0.30-0.50, and a PEEP of at least 10. This tidal volume or inspiratory pressure, for VC and PC ventilation respectively, will then be titrated down to meet a goal plateau pressure of less than or equal to 24 cmH2O, and a target driving pressure no greater than 14 cmH2O. Finally, the respiratory rate will then be titrated between 1 and 15 to meet the specified mechanical power goal range. Once the respiratory rate has been lowered to 8, tidal volumes (or inspiratory pressure required to meet this goal) will be lowered to 3cc/kg PBW prior to further reductions in respiratory rate. MP will be calculated every two hours and adjusted as needed to stay within the goal MP range until pre-specified weaning criteria are met.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Routine Care | No intervention | –This arm will receive routine care for all aspects of care including ECMO and mechanical ventilation as decided by the attending physician. |
| Targeted Intervention | Experimental | Procedure: Mechanical Power Targeted VentilationThis group will have their mechanical ventilator settings adjusted by the study team to a target mechanical power of between 2-4 J/minute, closely mimicking the mechanical power of that required for healthy adult breathing. The adjustments will be made using the mechanical power ventilation formula with information specific to the person, titrating each of the variables historically associated with ventilator induced lung injury in tandem. The ventilator will be monitored and adjusted as needed every 2 hours for 7 days while patients are on ECMO. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- On VV ECMO for less than 24 hours at time of study consent
- Severe ARDS as the primary etiology of respiratory failure defined by:
- Age 18 or greater
Key exclusion criteria (8 listed)
- Have received ECMO for >24 hours
- Are on VV ECMO but are not mechanically ventilated, or are planned not to have/not require invasive mechanical ventilation for >24 hours
- Patient is pregnant
- Patient is a prisoner
- Receiving VV ECMO as a bridge to transplant or history of lung 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 |
|---|---|---|
| Mechanical Power Targeted VentilationFor patients assigned to the intervention arm, the patient will be placed on volume control (VC) or pressure control (PC) ventilation with either an initial tidal volume of 3-4cc/kg predicted body weight (PBW) (for VC) or inspiratory pressure required to reach the same tidal volume goal (for PC), FiO2 set between 0.30-0.50, and PEEP of at least 10. This tidal volume or inspiratory pressure, for VC and PC respectively, will then be titrated down to meet a goal plateau pressure of less than or equal to 24 cmH2O, and a target driving pressure no greater than 14 cmH2O. Finally, the respiratory rate will then be titrated between 1 and 15 to meet the specified mechanical power goal range. Once the respiratory rate has been lowered to 8, tidal volumes will be lowered to 3cc/kg PBW prior to further reductions in respiratory rate. Mechanical power (MP) will be calculated every two hours and adjusted as needed to stay within the goal MP range until pre-defined weaning criteria are met. | Procedure or surgery | Targeted Intervention |
Primary outcome
Feasibility of prospective, randomized mechanical power-based strategy to establish a causal relationship between MP and clinical outcomes.
Time frame: From enrollment to the end of the intervention window of 7 days.
The primary outcome is to assess the feasibility of the intervention protocol, as assessed by the number of patients adhering to mechanical power (MP) protocol, with a target adherence of >/= 90% of the intervention time spent within the assigned mechanical power range.
3 secondary outcomes
To evaluate the safety of a total lung protective ventilation strategy utilizing a mechanical power targeted strategy versus conventional ultra-low tidal volume ventilation.
Time frame: From enrollment to end of intervention window of 7 days
To evaluate the tolerability of a total lung protective ventilation strategy utilizing a mechanical power targeted strategy versus conventional ultra-low tidal volume ventilation.
Time frame: From enrollment to end of intervention window of 7 days
To evaluate the tolerability of a total lung protective ventilation strategy utilizing a mechanical power targeted strategy versus conventional ultra-low tidal volume ventilation.
Time frame: From enrollment to end of intervention window of 7 days
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 1 Sep 2026.
- Background: PubMed 32448370van der Zee P, Rietdijk W, Somhorst P, Endeman H, Gommers D. A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality. Crit Care. 2020 May 24;24(1):243. doi: 10.1186/s13054-020-02913-7.
- Background: PubMed 32504104Tonna JE, Peltan I, Brown SM, Herrick JS, Keenan HT; University of Utah Mechanical Power Study Group. Mechanical power and driving pressure as predictors of mortality among patients with ARDS. Intensive Care Med. 2020 Oct;46(10):1941-1943. doi: 10.1007/s00134-020-06130-2. Epub 2020 Jun 5. No abstract available.
- Background: PubMed 40158848von During S, Liu K, Munshi L, Kim SJ, Urner M, Adhikari NKJ, Parhar KKS, Fan E. The Association Between Mechanical Power Within the First 24 Hours and ICU Mortality in Mechanically Ventilated Adult Patients With Acute Hypoxemic Respiratory Failure: A Registry-Based Cohort Study. Chest. 2025 Oct;168(4):901-911. doi: 10.1016/j.chest.2025.03.012. Epub 2025 Mar 28.
- Background: PubMed 39241350von During S, Parhar KKS, Adhikari NKJ, Urner M, Kim SJ, Munshi L, Liu K, Fan E. Understanding ventilator-induced lung injury: The role of mechanical power. J Crit Care. 2025 Feb;85:154902. doi: 10.1016/j.jcrc.2024.154902. Epub 2024 Sep 5.
- Background: PubMed 30291378Serpa Neto A, Deliberato RO, Johnson AEW, Bos LD, Amorim P, Pereira SM, Cazati DC, Cordioli RL, Correa TD, Pollard TJ, Schettino GPP, Timenetsky KT, Celi LA, Pelosi P, Gama de Abreu M, Schultz MJ; PROVE Network Investigators. Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts. Intensive Care Med. 2018 Nov;44(11):1914-1922. doi: 10.1007/s00134-018-5375-6. Epub 2018 Oct 5.
- Background: PubMed 27620287Gattinoni L, Tonetti T, Cressoni M, Cadringher P, Herrmann P, Moerer O, Protti A, Gotti M, Chiurazzi C, Carlesso E, Chiumello D, Quintel M. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016 Oct;42(10):1567-1575. doi: 10.1007/s00134-016-4505-2. Epub 2016 Sep 12.
- Background: PubMed 31144997Schmidt M, Pham T, Arcadipane A, Agerstrand C, Ohshimo S, Pellegrino V, Vuylsteke A, Guervilly C, McGuinness S, Pierard S, Breeding J, Stewart C, Ching SSW, Camuso JM, Stephens RS, King B, Herr D, Schultz MJ, Neuville M, Zogheib E, Mira JP, Roze H, Pierrot M, Tobin A, Hodgson C, Chevret S, Brodie D, Combes A. Mechanical Ventilation Management during Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome. An International Multicenter Prospective Cohort. Am J Respir Crit Care Med. 2019 Oct 15;200(8):1002-1012. doi: 10.1164/rccm.201806-1094OC.
- Background: PubMed 33965970Tonna JE, Abrams D, Brodie D, Greenwood JC, Rubio Mateo-Sidron JA, Usman A, Fan E. Management of Adult Patients Supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO J. 2021 Jun 1;67(6):601-610. doi: 10.1097/MAT.0000000000001432.
- Background: PubMed 38032683Qadir N, Sahetya S, Munshi L, Summers C, Abrams D, Beitler J, Bellani G, Brower RG, Burry L, Chen JT, Hodgson C, Hough CL, Lamontagne F, Law A, Papazian L, Pham T, Rubin E, Siuba M, Telias I, Patolia S, Chaudhuri D, Walkey A, Rochwerg B, Fan E. An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2024 Jan 1;209(1):24-36. doi: 10.1164/rccm.202311-2011ST.
- Background: PubMed 26903337Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
- Individual participant dataSharing planned: Yes. All de-identified IPD that underlie results in a publication.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mechanical Power Targeted Ventilation in people with ARDS (Acute Respiratory Distress Syndrome) and VV ECMO, run by University of Virginia 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: opening soon, as of the sponsor's last update on 1 Sep 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 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?
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 Ryan Lee, MD ((434) 924-9508, ZNN7YF@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of prospective, randomized mechanical power-based strategy to establish a causal relationship between MP and clinical outcomes. (time frame: From enrollment to the end of the intervention window of 7 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07790133, which also lists 10 linked publications.
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 1 Sep 2026.