Personalized Ventilator Settings for Patients on ECMO

NCT07673250 | Not Yet Recruiting DMC FDA Device

• 2 other identifiers: 8055931K23HL181397
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

While mechanical ventilation can be used to sustain life in those with lung injury, it, can further worsen lung injury or prevent lung healing resulting in high morbidity and mortality as seen in Acute Respiratory Distress Syndrome (ARDS). Using extracorporeal membrane oxygenation (ECMO), the highest level of life support also known as the heart-lung machine, investigators may minimize injury from mechanical ventilation to allow the lungs to heal; however, the optimal ventilator strategies while on ECMO are unknown. This study will evaluate personalized ventilator strategy compared to standard of care ventilation.

Conditions

Acute Respiratory Distress Syndrome (ARDS); Extracorporeal Membrane Oxygenation; Respiratory Failure Patients Treated With ECMO; Respiratory Failure, ICU; Ventilator Induced Lung Injury

Keywords

Respiratory failure; ARDS; Acute Respiratory Distress Syndrome; ECMO; Pneumonia; Lung injury; Influenza; COVID; Viruses; Personalized ventilator settings; Positive end expiratory pressure; PEEP

Outcome Measures

Primary Outcomes (3)

• Biomarker outcomes (IL-6 and sRAGE)

  IL-6 is a marker of systemic inflammation, previously used in studies of ECMO and ARDS. sRAGE is a marker of systemic inflammation and acute lung injury, previously used in studies of ECMO and ARDS.

  Baseline at enrollment, 24±12 hours post enrollment, 48±12 hours post enrollment, 72±12 hours post enrollment, and end of ECMO run.

• Respiratory gas exchange (dead space, oxygenation).

  Arterial oxygenation (mmHg) will be assessed with the arterial blood gas. Deadspace fraction (unitless) will be calculated by the end-title CO2 monitoring.

  Baseline at enrollment, 24±12 hours post enrollment, 48±12 hours post enrollment, 72±12 hours post enrollment.

• Respiratory mechanics (compliance of the respiratory system, tidal volume, and imaging)

  Compliance (ml/cmH2O) and tidal volumes (milliliters) will be measured by the ventilator. Imaging assessed will be the daily chest x-ray.

  Baseline at enrollment, 24±12 hours post enrollment, 48±12 hours post enrollment, and 72±12 hours post enrollment.

Secondary Outcomes (1)

• Exploratory plasma, urine, and respiratory biomarkers.

  Baseline at enrollment, 24±12 hours post enrollment, 48±12 hours post enrollment, 72±12 hours post enrollment, and end of ECMO run.

Study Arms (2)

Standard of Care Ventilator Settings while on ECMO

NO INTERVENTION

Classic ventilator settings for patients on ECMO. Pressure control, with a respiratory rate of 10, driving pressure of 10, and PEEP of 10.

Personalized PEEP

EXPERIMENTAL

Classic ventilator settings for patients on ECMO. Pressure control, with a respiratory rate of 10, driving pressure of 10, and a personalized PEEP (intervention)

Device: Personalized Positive End-Expiratory Pressure (PEEP)

Interventions

Personalized Positive End-Expiratory Pressure (PEEP) DEVICE

The personalized Positive End-Expiratory Pressure (PEEP) will be determined by esophageal manometry or electrical impedance tomography (EIT)

Also known as: Esophageal manometry, Titration of PEEP by end-expiratory transpulmonary pressure, Titration of PEEP by electrical impedance tomography (EIT)

Personalized PEEP

Eligibility Criteria

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

1. History of Lung or Cardiac Transplantation, or definite bridge to transplantation 2. Patient is not committed to full support 3. Treating clinician refusal, or unwillingness to commit to controlled therapeutics (Esophageal Pressure Guided Positive End-Expiratory Pressure and neuromuscular blockade) 4. Inability to get informed consent from the patient or legally authorized representative (LAR) 5. Patients with contraindications to esophageal balloon placement or inability to successfully place an esophageal balloon will have personalized PEEP determined by electrical impedance tomography. a. Contraindications include recently treated or bleeding varices, esophageal stricture, hematemesis, esophageal trauma, recent esophageal surgery or other contraindication for nasogastric tube placement, or severe coagulopathy. 6. Severe barotrauma that requires lower mean airway pressure (i.e., PEEP) per the treating physician. 7. Patients who are pregnant or prisoners. 8. Has been on V-V ECMO \> 72 hours.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Diego: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UC San Diego Health Jacobs Medical Center

La Jolla, California, 92037, United States

Location

Related Publications (11)

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• Dianti J, Tisminetzky M, Ferreyro BL, Englesakis M, Del Sorbo L, Sud S, Talmor D, Ball L, Meade M, Hodgson C, Beitler JR, Sahetya S, Nichol A, Fan E, Rochwerg B, Brochard L, Slutsky AS, Ferguson ND, Serpa Neto A, Adhikari NKJ, Angriman F, Goligher EC. Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis. Am J Respir Crit Care Med. 2022 Jun 1;205(11):1300-1310. doi: 10.1164/rccm.202108-1972OC.

  PMID: 35180042 BACKGROUND

• Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring SH. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008 Nov 13;359(20):2095-104. doi: 10.1056/NEJMoa0708638. Epub 2008 Nov 11.

  PMID: 19001507 BACKGROUND

• Brodie D, Slutsky AS, Combes A. Extracorporeal Life Support for Adults With Respiratory Failure and Related Indications: A Review. JAMA. 2019 Aug 13;322(6):557-568. doi: 10.1001/jama.2019.9302.

  PMID: 31408142 BACKGROUND

• Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, Maury E, Levy B, Cohen Y, Richard C, Kalfon P, Bouadma L, Mehdaoui H, Beduneau G, Lebreton G, Brochard L, Ferguson ND, Fan E, Slutsky AS, Brodie D, Mercat A; EOLIA Trial Group, REVA, and ECMONet. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018 May 24;378(21):1965-1975. doi: 10.1056/NEJMoa1800385.

  PMID: 29791822 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

• Beitler JR, Sarge T, Banner-Goodspeed VM, Gong MN, Cook D, Novack V, Loring SH, Talmor D; EPVent-2 Study Group. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure-Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2019 Mar 5;321(9):846-857. doi: 10.1001/jama.2019.0555.

  PMID: 30776290 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

• Lam MTY, Duttke SH, Odish MF, Le HD, Hansen EA, Nguyen CT, Trescott S, Kim R, Deota S, Chang MW, Patel A, Hepokoski M, Alotaibi M, Rolfsen M, Perofsky K, Warden AS, Foley J, Ramirez SI, Dan JM, Abbott RK, Crotty S, Crotty Alexander LE, Malhotra A, Panda S, Benner CW, Coufal NG. Dynamic activity in cis-regulatory elements of leukocytes identifies transcription factor activation and stratifies COVID-19 severity in ICU patients. Cell Rep Med. 2023 Feb 21;4(2):100935. doi: 10.1016/j.xcrm.2023.100935. Epub 2023 Jan 25.

  PMID: 36758547 BACKGROUND

• Odish MF, Yang J, Cheng G, Yi C, Golts E, Madani M, Pollema T, Owens RL. Treatment of Bronchopleural and Alveolopleural Fistulas in Acute Respiratory Distress Syndrome With Extracorporeal Membrane Oxygenation, a Case Series and Literature Review. Crit Care Explor. 2021 May 14;3(5):e0393. doi: 10.1097/CCE.0000000000000393. eCollection 2021 May.

  PMID: 34036268 BACKGROUND

• Odish M, Pollema T, Meier A, Hepokoski M, Yi C, Spragg R, Patel HH, Alexander LEC, Sun XS, Jain S, Simonson TS, Malhotra A, Owens RL. Very Low Driving-Pressure Ventilation in Patients With COVID-19 Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation: A Physiologic Study. J Cardiothorac Vasc Anesth. 2023 Mar;37(3):423-431. doi: 10.1053/j.jvca.2022.11.033. Epub 2022 Nov 28.

  PMID: 36567221 BACKGROUND

MeSH Terms

Conditions

Respiratory Distress Syndrome; Respiratory Insufficiency; Ventilator-Induced Lung Injury; Pneumonia; Lung Injury; Influenza, Human; Virus Diseases

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Respiratory Tract Infections; Infections; Thoracic Injuries; Wounds and Injuries; Orthomyxoviridae Infections; RNA Virus Infections

Study Officials

• Mazen F Odish, M.D.

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mazen F Odish, M.D.

CONTACT

858-657-7023; modish@health.ucsd.edu

Robert L Owens, M.D.

CONTACT

858-657-5258; rowens@health.ucsd.edu

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: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: June 27, 2025
• First Posted: June 29, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2031
• Last Updated: June 29, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)