Physiological Effects of Continuous Negative External Pressure for Acute Hypoxemic Respiratory Failure

Physiological Effects of Continuous Negative External Pressure for Acute Hypoxemic Respiratory Failure: A Pilot Crossover Trial

This study is being conducted to evaluate if wearing a non-invasive breathing support device over the chest/abdomen improves markers of breathing in patients with lung injury requiring high-flow oxygen. The breathing support device consists of a plastic shell that sits over the chest and abdomen and connects to a vacuum that helps the chest expand with breathing. This breathing support is known as continuous negative external pressure (CNEP). Study findings will help determine if this breathing support device might be useful for patients with acute hypoxemic respiratory failure (AHRF).

Study Overview

• Status: Recruiting
• Conditions: Acute Hypoxemic Respiratory Failure
• Intervention / Treatment: Device: HFNC only; Device: HFNC + CNEP10; Device: HFNC + CNEP20; Device: HFNC + CNEP30

Detailed Description

This study is a prospective randomized cross-over trial. Eligible, consenting participants will undergo 4 strategies of respiratory support: high-flow nasal cannula (HFNC) only, HFNC + continuous negative external pressure (CNEP) of 10 cmH2O, HFNC + CNEP of 20 cmH2O, HFNC + CNEP of 30 cmH2O. Throughout the study period, HFNC will be managed at a constant flow rate with fraction of inspired oxygen (FiO2) titrated to achieve goal oxygen saturation (SpO2) of 90-97%, measured via continuous pulse-oximetry. Each of the 4 strategies will be performed for 45 minutes per strategy, interspersed with a 15-minute washout period of HFNC only. Participants will be randomized to the sequence of strategies for respiratory support.

A summary of the sequence of trial procedures is as follows:

1. Perform baseline measures.
2. Wait 5-10 minutes for recovery.
3. Initiate first random treatment assignment for up to 45 minutes.
4. HFNC-only washout for 15 minutes
5. Initiate second random treatment assignment for up to 45 minutes.
6. HFNC-only washout for 15 minutes
7. Initiate third random treatment assignment for up to 45 minutes.
8. HFNC-only washout for 15 minutes
9. Initiate fourth random treatment assignment for up to 45 minutes.
10. Return to usual care (HFNC only)

If a participant does not tolerate a given level of CNEP, the patient will be returned to HFNC for 5 minutes and then given the option to attempt that CNEP level again. If the patient declines reattempt or does not tolerate that CNEP level on reattempt, the HFNC-only washout will be instituted for 15 minutes before proceeding to the next protocol step.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jeremy Beitler, MD, MPH; Phone Number: 212-305-0334; Email: jrb2266@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Jeremy Beitler, MD, MPH; Phone Number: 212-305-0334; Email: jrb2266@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older
• Acute hypoxemic respiratory failure
• Non-cardiogenic airspace opacities on chest radiograph or computed tomography (CT) scan
• High-flow nasal cannula (flow ≥ 30 LPM) initiated within last 96 hours (4 days)
• FiO2 ≥ 40%
• SpO2 ≥ 92%

Exclusion Criteria:

• Do-not-intubate order
• Anatomical factor predisposing to poor fit of cuirass (e.g. severe kyphosis or scoliosis)

• Use of cuirass precluded, e.g. due to:

  • Clinically prescribed prone positioning
  • Tense ascites
  • Severe abdominal pain
  • Abdominal wound or surgery
  • Pregnancy
  • Agitated delirium
• Prior intubation during hospital stay
• Cardiogenic pulmonary edema
• Exacerbation of asthma or COPD

• Chronic lung disease, including:

  • Interstitial lung disease
  • Cystic fibrosis
  • Lung mass, lung cancer, or metastasis to the lung
  • Lung transplant recipient
  • Any disease that requires home oxygen
• Glasgow coma score < 15
• Chest tube, pneumothorax, or pneumomediastinum
• Hemodynamic instability (mean arterial pressure < 55 mmHg or norepinephrine-equivalent vasopressor requirement > 0.1mcg/kg/min)
• Implantable electrical device (e.g. pacemaker, defibrillator, neurostimulator)
• Unreliable pulse-oximetry tracing
• Imminent intubation
• Anticipated lack of patient availability to complete study procedures (e.g. due to planned clinical procedure such as CT scan or dialysis during potential time of study)
• Attending physician refusal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HFNC only	Device: HFNC only; HFNC for 45 minutes, with FiO2 titrated to SpO2 of 90-97%
Experimental: HFNC + CNEP10	Device: HFNC + CNEP10; HFNC with CNEP of 10 cmH2O for 45 minutes, with FiO2 titrated to SpO2 of 90-97%
Experimental: HFNC + CNEP20	Device: HFNC + CNEP20; HFNC with CNEP of 20 cmH2O for 45 minutes, with FiO2 titrated to SpO2 of 90-97%
Experimental: HFNC + CNEP30	Device: HFNC + CNEP30; HFNC with CNEP of 30 cmH2O for 45 minutes, with FiO2 titrated to SpO2 of 90-97%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in SpO2/FiO2	The change in SpO2/FiO2 within each participant as measured at baseline and at the end of each treatment assignment period. The average SpO2/FiO2 over the last five minutes of the treatment period will be used.	At the end of each treatment period, up to 45 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Respiratory Rate	The change in Respiratory Rate within each participant as measured at baseline and at the end of each treatment assignment period. The average Respiratory Rate over the last five minutes of the treatment period will be used.	At the end of each treatment period, up to 45 minutes
Change from baseline in ROX Index	The change in ROX index within each participant as measured at baseline and at the end of each treatment assignment period. ROX index is calculated as SpO2/FiO2 divided by the Respiratory Rate. The average ROX index over the last five minutes of the treatment period will be used.	At the end of each treatment period, up to 45 minutes
Change from baseline in Transcutaneous Carbon Dioxide (CO2)	The change in Transcutaneous Carbon Dioxide within each participant as measured at baseline and at the end of each treatment assignment period. The average Transcutaneous Carbon Dioxide over the last five minutes of the treatment period will be used.	At the end of each treatment period, up to 45 minutes
Change from baseline in Heart Rate	The change in Heart Rate within each participant as measured at baseline and at the end of each treatment assignment period. The average Heart Rate over the last five minutes of the treatment period will be used.	At the end of each treatment period, up to 45 minutes
Change from baseline in Blood Pressure	The change in Blood Pressure within each participant as measured at baseline and at the end of each treatment assignment period. The average Blood Pressure over the last five minutes of the treatment period will be used.	At the end of each treatment period, up to 45 minutes
Change from baseline in Breathing Discomfort	The change in Breathing Discomfort within each participant as measured at baseline and at the end of each treatment assignment period. Breathing Discomfort will be measured with component A1 of the Multidimensional Dyspnea Profile.	At the end of each treatment period, up to 45 minutes
Change from baseline in Lightheadedness	The change in Lightheadedness within each participant as measured at baseline and at the end of each treatment assignment period. Lightheadedness will be measured with an ordinal scale ranging from 0 to 10.	At the end of each treatment period, up to 45 minutes
Change from baseline in Nausea	The change in Nausea within each participant as measured at baseline and at the end of each treatment assignment period. Nausea will be measured with an ordinal scale ranging from 0 to 10.	At the end of each treatment period, up to 45 minutes
Change from baseline in Skin Discomfort	The change in patient-reported Skin Discomfort as measured at baseline and at the end of each treatment assignment period. Skin Discomfort will be measured with an ordinal scale ranging from 0 to 10.	At the end of each treatment period, up to 45 minutes
Change from baseline in Skin Erythema	The change in Skin Erythema within each participant as measured at baseline and at the end of each treatment assignment period. Skin erythema will be measured by investigator visual assessment using a five-point scale.	At the end of each treatment period, up to 45 minutes
Tolerance of intervention period	Patient able to complete the entire treatment period of intervention without early discontinuation for intolerance	For the duration of each treatment period, up to 45 minutes
Proportion of time within 3 cm H2O of target CNEP level	Ability to reach and maintain the target CNEP level, defined as CNEP within ± 3 cm H2O of the prescribed value	For the duration of each treatment period, up to 45 minutes
Proportion of time within 5 cm H2O of target CNEP level	Ability to reach and maintain the target CNEP level, defined as CNEP within ± 5 cm H2O of the prescribed value	For the duration of each treatment period, up to 45 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in other components of the Multidimensional Dyspnea Profile	The change in other components of the Multidimensional Dyspnea Profile within each participant as measured at baseline and at the end of the study. At end of study, participants will be instructed to consider their breathing on average during CNEP to obtain the post-baseline measure.	At end of study
Change from baseline in Tidal Volume	The change in Tidal Volume within each participant as measured at baseline and at the end of each treatment assignment period, estimated from lung electrical impedance tomography. The average Tidal Volume over the last five minutes of the treatment period will be used.	At the end of each treatment period, up to 45 minutes
Change from baseline in End-Expiratory Lung Volume	The change in End-Expiratory Lung Volume within each participant as estimated from end-expiratory lung impedance measured at baseline and at the end of each treatment assignment period. The average End-Expiratory Lung Impedance over the last five minutes of the treatment period will be used to derive change in end-expiratory lung volume.	At the end of each treatment period, up to 45 minutes
Change from baseline in Minute Ventilation	The change in Minute Ventilation within each participant as measured at baseline and at the end of each treatment assignment period, estimated from lung electrical impedance tomography. The average Minute Ventilation over the last five minutes of the treatment period will be used.	At the end of each treatment period, up to 45 minutes
Change from baseline in Anteroposterior Ventilation Ratio	The change in Anteroposterior Ventilation Ratio within each participant as measured at baseline and at the end of each treatment assignment period, estimated from lung electrical impedance tomography. The average Anteroposterior Ventilation Ratio over the last five minutes of the treatment period will be used.	At the end of each treatment period, up to 45 minutes

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Jeremy Beitler, MD, MPH, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 29, 2022
• First Submitted That Met QC Criteria: December 29, 2022
• First Posted (Actual): January 9, 2023

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: atelectasis; mechanical ventilation; noninvasive ventilation; acute respiratory distress syndrome; high-flow nasal cannula; oxygen inhalation therapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: AAAT7361

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes