Trial Outcomes & Findings for Providing Optimal PEEP During Mechanical Ventilation for Obese Patients Using Esophageal Balloon (NCT NCT03951064)

NCT ID: NCT03951064

Last Updated: 2024-06-05

Results Overview

The number of days a patient is alive and free from the ventilator up to day 28.

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 6 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2024-06-05

Participant Flow

Participant milestones

Measure	Optimal Post End Expiratory Pressure (PEEP) Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and Post End Expiratory Pressure (PEEP) setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm water (H2O) and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve.	ARDSNet High PEEP Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and fraction of inspired oxygen (FiO2) Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Overall Study STARTED	3	3
Overall Study COMPLETED	3	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Providing Optimal PEEP During Mechanical Ventilation for Obese Patients Using Esophageal Balloon

Baseline characteristics by cohort

Measure	Optimal PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.	Total n=6 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days

The number of days a patient is alive and free from the ventilator up to day 28.

Outcome measures

Measure	Optimal PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Number of Ventilator-Free Days (VFD) by Day 28	2.33 Days Standard Deviation 5.86	6.67 Days Standard Deviation 13.32

SECONDARY outcome

Timeframe: 72 hours after extubation

Intubated within 72 hours of extubation

Outcome measures

Measure	Optimal PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Number of Participants Reintubated	2 Participants	1 Participants

SECONDARY outcome

Timeframe: maximum duration of ICU stay, up to 46 days

Number of days spent in the ICU

Outcome measures

Measure	Optimal PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
ICU Length of Stay	37.33 Days Standard Deviation 7.77	24.00 Days Standard Deviation 18.33

SECONDARY outcome

Timeframe: maximum duration of hospital stay, up to 83 days

Number of days spent in the Hospital

Outcome measures

Measure	Optimal PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Hospital Length of Stay	62.67 Days Standard Deviation 18.45	33.67 Days Standard Deviation 29.02

SECONDARY outcome

Timeframe: during mechanical ventilation, up to 28 days

Whether the patient required a tracheostomy to be liberated from the ventilator

Outcome measures

Measure	Optimal PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Number of Patients Receiving a Tracheostomy	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 28 days

Population: This measure only applies to the Control group. These data were not collected for the Optimal PEEP arm.

Extubation prior to meeting established criteria (Control group only). Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. This is the current standard of care based on the SBT protocol at UNC Hospitals. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking.

Outcome measures

Measure	Optimal PEEP Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Number of Patients Extubated Early	—	2 Participants

SECONDARY outcome

Timeframe: during mechanical ventilation, up to 28 days

Measures the mental and physical state of a sedated patient. Range from -5 to +4. A score of 0 indicates a calm arousable patient and is the ideal score. A score of +4 indicates a very combative participant and a score of -5 indicates an unarousable participant. This outcome captures the highest score measured throughout mechanical ventilation with scores on the extreme ends of the range reflecting a worse outcome.

Outcome measures

Measure	Optimal PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Highest Richmond Agitation and Sedation Scale	2.33 score on a scale Standard Deviation 0.58	2.00 score on a scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: during mechanical ventilation, up to 28 days

Measures the mental and physical state of a sedated patient. Range from -5 to +4. A score of 0 indicates a calm arousable patient and is the ideal score. A score of +4 indicates a very combative participant and a score of -5 indicates an unarousable participant. This outcome captures the lowest score measured throughout mechanical ventilation with scores on the extreme ends of the range reflecting a worse outcome.

Outcome measures

Measure	Optimal PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 Participants Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Lowest Richmond Agitation and Sedation Scale	-4.67 score on a scale Standard Deviation 0.58	-4.67 score on a scale Standard Deviation 0.58

Adverse Events

Optimal PEEP

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

ARDSNet High PEEP

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Measure	Optimal PEEP n=3 participants at risk Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 participants at risk Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Respiratory, thoracic and mediastinal disorders Pneumothorax	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).

Other adverse events

Measure	Optimal PEEP n=3 participants at risk Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. Mechanical ventilation settings were monitored daily and PEEP setting adjusted based on the balloon measurements. Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Intervention Spontaneous Breathing Trial (SBT) and Extubation: Participants undergo an SBT regardless of PEEP level. The PEEP that generates a Ptp of 0 was considered the optimal PEEP, and this will not be lowered for the SBT. The Intervention Group SBT will consist of a trial of a pressure support of 5 cm H2O and Optimal PEEP. Intervention Weaning after Tracheostomy: Based on the use of optimal PEEP in this group, and the experience in the previous study protocol, the investigators will place participants in the Intervention group on Tracheostomy Collar Trial only with a speaking valve. This simulates the normal process of utilizing the upper airway to maintain lung inflation that is performed automatically when a participant does not have an artificial airway.	ARDSNet High PEEP n=3 participants at risk Obese adult participants presenting to the ICU with acute respiratory failure requiring mechanical ventilation were enrolled. PEEP in the control group will be determined by High PEEP ARDSnet PEEP/FiO2 table. Titration of PEEP will occur when clinically indicated by partial pressure of oxygen (PaO2) or oxygen saturation (SpO2), and FiO2 Esophageal balloon: Participants will have an esophageal balloon catheter inserted by a research investigator. The catheter will be inserted into the nare while upright (head of bed \>30 degrees) to a depth slightly more than the estimated distance from the lower sternum to the back of the ear (typically around 60 cm). Placement confirmed with the presence of cardiac oscillations on the esophageal probe. The probe will then be secured to the nasal opening using tape. Control Spontaneous Breathing Trial and Extubation: Participants in the Control group will undergo an SBT when they reach a PEEP ≤8 cm H2O. SBT and extubation prior to meeting these criteria will be based on primary medical team's discretion and will be recorded for analysis and safety tracking. Control Weaning after Tracheostomy: The control group will be placed on Tracheostomy Collar Trial with no requirement for speaking valve. They may utilize a speaking valve if tolerated and desired, but there is no requirement as there is in the Intervention group.
Renal and urinary disorders Renal failure	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).
Respiratory, thoracic and mediastinal disorders Emphysema	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).
Respiratory, thoracic and mediastinal disorders Atelectasis	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).
Renal and urinary disorders Elevated creatinine kinase	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).
Skin and subcutaneous tissue disorders Folliculitis	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).
Metabolism and nutrition disorders Hypophosphatemia	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).
Blood and lymphatic system disorders Thrombocytopenia	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).
Infections and infestations Thrush	33.3% 1/3 • Number of events 1 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).	0.00% 0/3 • From the time of signing the informed consent through 28 days of mechanical ventilation or successful extubation (whichever occurred first).

Additional Information

Jackson Pettee

University of North Carolina at Chapel Hill

Phone: 984-215-6872

Email: jackson_pettee@med.unc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place