Adiposity Distribution in Acute Respiratory Failure

NCT07019987 | Not Yet Recruiting DMC

• 1 other identifier: 2025P001410
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Acute Hypoxemic Respiratory Failure (AHRF) is a condition in which injury to the lungs impairs the ability of the air sacs (alveoli) to ventilate and exchange oxygen. This impairment may be worsened in individuals with elevated body weight, particularly when fat tissue compresses the lungs and promotes alveolar collapse. The impact of body weight on lung function may be greater in individuals with upper-body fat distribution. Two common interventions for AHRF-positive end-expiratory pressure (PEEP) and prone positioning-are used to improve lung ventilation. However, it is unclear whether these therapies are equally effective across different body weight categories and fat distributions. This study will evaluate whether body weight and fat distribution affect patients' lung inflation responses to PEEP and prone positioning. Lung inflation will be assessed using electrical impedance tomography (EIT), a bedside imaging tool that maps lung ventilation, and esophageal manometry, which estimates lung compression through a thin catheter placed in the esophagus. Laboratory tests will also be used to measure markers of inflammation and AHRF severity and find correlations with fat distribution and responses to the tested treatments.. Patients with AHRF requiring mechanical ventilation will be enrolled across a range of body weights. Each participant will undergo combinations of two PEEP levels and two body positions (supine and prone) for 30 minutes each. At the end of the study procedures, clinical care will continue as determined by the treating team.

Conditions

Acute Hypoxemic Respiratory Failure; Obesity

Keywords

acute hypoxemic respiratory failure; obesity; electrical impedance tomography; esophageal manometry; mechanical ventilation; prone positioning; positive end expiratory pressure

Outcome Measures

Primary Outcomes (1)

• Driving pressure with PEEP titration and prone position

  The primary outcome will be the difference in driving pressure (inspiratory plateau pressure minus total PEEP, in cmH2O) in response to PEEP titration strategies and to prone position. Changes in driving pressure will be correlated with body mass index, and with measurements of thoracic, and abdominal circumference.

  Day 1, after 30 minutes in each combination of PEEP and body position

Secondary Outcomes (1)

• Regional ventilation

  Day 1, after 30 minutes in each combination of PEEP and body position

Other Outcomes (26)

• Age

  Day 1

• Height

  Day 1

• Weight

  Day 1

Study Arms (1)

Single Arm: Ventilatory Assessment at Two PEEP Levels and Body Positions

EXPERIMENTAL

A total of 80 patients will undergo sequential assessments during mechanical ventilation at two levels of PEEP: 1. Clinician-set PEEP (PEEP\_CLIN) 2. PEEP determined by EIT-guided titration (PEEP\_TIT) These interventions will be applied first in the supine position, with each PEEP level maintained for approximately 30 minutes. Afterward, patients will be repositioned to the prone position, and the same assessments and EIT-guided PEEP titration will be repeated.

Other: PEEP Titration Using Electrical Impedance Tomography (EIT); Procedure: Body Positioning: Supine and Prone

Interventions

PEEP Titration Using Electrical Impedance Tomography (EIT) OTHER

EIT will be used to guide individualized PEEP titration in mechanically ventilated patients with AHRF. Each subject will receive mechanical ventilation at two PEEP levels: PEEP\_CLIN (set by the treating clinician) PEEP\_TIT (identified using EIT to minimize alveolar collapse and overdistension) Both levels will be maintained for 30 minutes in each body position, with continuous physiologic data collected during each phase.

Single Arm: Ventilatory Assessment at Two PEEP Levels and Body Positions

Body Positioning: Supine and Prone PROCEDURE

Each subject will be ventilated in both the supine and prone positions. Positioning will follow institutional protocols and be coordinated with clinical staff to ensure safety. After supine assessments are completed, the patient will be transitioned to prone, followed by a recruitment maneuver to standardize lung volume history. The PEEP titration protocol will then be repeated in the prone position.

Single Arm: Ventilatory Assessment at Two PEEP Levels and Body Positions

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AHRF with PaO2/FiO2 \<= 300 mmHg) intubated for less than 72 hours
• Presence of an arterial line for blood gas measurement and blood pressure monitoring
• years or older

You may not qualify if:

• Suspected pregnancy, pregnancy or less than six weeks postpartum
• Younger than 18 years or older than 80 years.
• Subject enrolled in another interventional research study
• Presence of pneumothorax
• Usage of any devices with electric current generation such as pacemaker or internal cardiac defibrillator
• Preexisting chronic lung disease or pulmonary hypertension
• Acute cardiac failure causing pulmonary edema
• Past medical history of lung malignancy or pneumonectomy, or lung transplant
• Hemodynamic instability, defined as:
• Persistent systolic blood pressure \<90 mmHg and/or \>180 mmHg despite the use of vasopressor or vasodilators, or
• Requiring an increment in inotropic-vasopressors over the past two hours just before enrollment: more than 15 mcg/min for norepinephrine and dopamine, more than 10 mcg/min in epinephrine; and more than 50 mcg/ min for phenylephrine.
• Contraindications to placement in the prone position: complex abdominal surgical dressing, recent sternotomy, unstable spine or pelvic fractures, intracranial hypertension, serious facial injury
• Extracorporeal life support

Sponsors & Collaborators

• Maurizio F. Cereda, MD: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (6)

• Hao D, Low S, Di Fenza R, Shenoy ES, Ananian L, Prout LA, La Vita CJ, Berra L. Prone Positioning of Intubated Patients with an Elevated Body-Mass Index. N Engl J Med. 2022 Apr 7;386(14):e34. doi: 10.1056/NEJMvcm2108494. No abstract available.

  PMID: 35388669 BACKGROUND

• Kompaniyets L, Goodman AB, Belay B, Freedman DS, Sucosky MS, Lange SJ, Gundlapalli AV, Boehmer TK, Blanck HM. Body Mass Index and Risk for COVID-19-Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death - United States, March-December 2020. MMWR Morb Mortal Wkly Rep. 2021 Mar 12;70(10):355-361. doi: 10.15585/mmwr.mm7010e4.

  PMID: 33705371 BACKGROUND

• Behazin N, Jones SB, Cohen RI, Loring SH. Respiratory restriction and elevated pleural and esophageal pressures in morbid obesity. J Appl Physiol (1985). 2010 Jan;108(1):212-8. doi: 10.1152/japplphysiol.91356.2008. Epub 2009 Nov 12.

  PMID: 19910329 BACKGROUND

• De Santis Santiago R, Teggia Droghi M, Fumagalli J, Marrazzo F, Florio G, Grassi LG, Gomes S, Morais CCA, Ramos OPS, Bottiroli M, Pinciroli R, Imber DA, Bagchi A, Shelton K, Sonny A, Bittner EA, Amato MBP, Kacmarek RM, Berra L; Lung Rescue Team Investigators. High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial. Am J Respir Crit Care Med. 2021 Mar 1;203(5):575-584. doi: 10.1164/rccm.201909-1687OC.

  PMID: 32876469 BACKGROUND

• Florio G, De Santis Santiago RR, Fumagalli J, Imber DA, Marrazzo F, Sonny A, Bagchi A, Fitch AK, Anekwe CV, Amato MBP, Arora P, Kacmarek RM, Berra L. Pleural Pressure Targeted Positive Airway Pressure Improves Cardiopulmonary Function in Spontaneously Breathing Patients With Obesity. Chest. 2021 Jun;159(6):2373-2383. doi: 10.1016/j.chest.2021.01.055. Epub 2021 May 8.

  PMID: 34099131 BACKGROUND

• Spina S, Mantz L, Xin Y, Moscho DC, Ribeiro De Santis Santiago R, Grassi L, Nova A, Gerard SE, Bittner EA, Fintelmann FJ, Berra L, Cereda M. The pleural gradient does not reflect the superimposed pressure in patients with class III obesity. Crit Care. 2024 Sep 16;28(1):306. doi: 10.1186/s13054-024-05097-6.

  PMID: 39285477 BACKGROUND

MeSH Terms

Conditions

Respiratory Insufficiency; Obesity

Interventions

Prone Position

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Posture; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Maurizio F Cereda, MD

CONTACT

16176430987; mcereda@mgh.harvard.edu

Lorenzo Berra, MD

CONTACT

617 724 0743; LBERRA@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Anesthesia

Model Details: In a prospective, single-center, physiological, crossover study, the investigators will recruit 80 mechanically ventilated adults with acute hypoxemic respiratory failure, across four standard body mass index categories (normal weight, overweight, class I obesity, class II/III obesity) and sex.

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: June 13, 2025
• Study Start (Estimated): January 1, 2028
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): June 30, 2030
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)