Prospective Randomized Trial of Total Lung Protective Ventilation in Adult VV-ECMO Patients With Severe ARDS

NCT07790133 | Not Yet Recruiting DMC

• 2 other identifiers: HSR 303640FP00429174
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

ARDS (Acute Respiratory Distress Syndrome); VV ECMO

Keywords

ARDS; VV ECMO; Mechanical Power; Ventilator Induced Lung Injury

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  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.

  From enrollment to end of intervention window of 7 days

Other Outcomes (11)

• Exploratory additional outcomes

  From enrollment to end of intervention window at day 7.

• Exploratory additional outcomes

  From enrollment to end of study participation (post hospitalization visit 12 weeks after discharge.)

• Exploratory additional outcomes

  From enrollment to end of study participation (post hospitalization visit 12 weeks after discharge.)

Study Arms (2)

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.

Procedure: Mechanical Power Targeted Ventilation

Interventions

Mechanical Power Targeted Ventilation PROCEDURE

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.

Targeted Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Related Publications (10)

• 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.

  PMID: 32448370 BACKGROUND

• Tonna 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.

  PMID: 32504104 BACKGROUND

• von 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.

  PMID: 40158848 BACKGROUND

• von 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.

  PMID: 39241350 BACKGROUND

• Serpa 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.

  PMID: 30291378 BACKGROUND

• Gattinoni 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.

  PMID: 27620287 BACKGROUND

• Schmidt 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.

  PMID: 31144997 BACKGROUND

• Tonna 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.

  PMID: 33965970 BACKGROUND

• Qadir 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.

  PMID: 38032683 BACKGROUND

• Bellani 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.

  PMID: 26903337 BACKGROUND

MeSH Terms

Conditions

Acute Lung Injury; Ventilator-Induced Lung Injury

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Ryan Lee, MD

CONTACT

(434) 924-9508; ZNN7YF@uvahealth.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ryan Lee, MD, Assistant Professor of Anesthesiology and Emergency Medicine, Division of Critical Care

Study Record Dates

• First Submitted: August 13, 2026
• First Posted: August 27, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 27, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 2 years after the publication of results.

Locations

US (1)