Respiratory Muscle Structure and Function in Mechanically Ventilated Patients and Long-term Outcomes

Respiratory Insufficiency Clinical Trial

— RESPIRE  

Official title:

Respiratory Muscle Structure and Function in Mechanically Ventilated Patients and Long-term Outcomes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05857774
• Other study ID #: 22-5875
• Status: Recruiting
• Start date: April 27, 2023
• Est. completion date: June 30, 2026

Study information

• Verified date: May 2024
• Source: University Health Network, Toronto
• Contact: Rongyu (Cindy) Jin
• Phone: 4163404800
• Email: rongyu.jin[@]uhn.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Air is normally pumped in and out of the lungs by the muscles that contribute to inhalation and exhalation, called the respiratory muscles. The abdominal muscles help by forcing air out of your lungs during exhalation; whereas the diaphragm, the main muscle used for breathing, contracts to get air into the lungs during inhalation. With mechanical ventilation, respiratory muscles are able to rest and recover while the breathing machine takes over; however, this may cause respiratory muscle weakness. Patients who develop weakness of these muscles may require more assistance from the ventilator and take longer to recover their ability to breathe without assistance. The impact of this phenomenon on long-term outcomes is uncertain.

The RESPIRE study is designed to characterize how respiratory muscles change during mechanical ventilation and to evaluate the impact on long term quality of life. An additional objective of this study is to examine novel measures obtained from automated functions of a ventilator, that may better predict success from weaning from mechanical ventilation.

Description:

Previous work has established that diaphragm atrophy during mechanical ventilation is associated with adverse clinical outcomes. Abdominal muscles, which are engaged during breathing also undergo atrophy during mechanical ventilation. However, the relationship between these muscles and how they relate to long term function status is known and warrants further investigation.

Mechanical ventilation is a life-saving technique in patients with respiratory failure, however reasons why some patients require long term ventilation and are unsuccessful from weaning from ventilators are not fully elucidated. Respiratory muscle dysfunction as a result of mechanical ventilation is only recently being understood. Diaphragm atrophy is associated with adverse clinical outcomes, but the same is unknown if this holds true with abdominal muscle atrophy. Properly understanding the natural progression of diaphragm and abdominal muscle atrophy and dysfunction, and how they relate to each other, is critical to identifying markers or factors that may put particular patients at risk for long durations of mechanical ventilation and adverse clinical outcomes.

This study will provide important insights into the relationship between inspiratory and expiratory muscle function, and the evolution of functional impairments in critical care patients undergoing weaning from invasive mechanical ventilation. Further understanding of the pathophysiological processes of how these muscle groups interact in this context is important in moving forward with potential therapeutic strategies aimed at mitigating injury.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: June 30, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Cases Inclusion Criteria:

• Adult patients =18 years of age undergoing invasive mechanical ventilation in the ICU for any reason within 36 hours of intubation

Control condition A Inclusion Criteria:

• Non-invasively ventilated patients in the ICU within 36 hours of initiating non-invasive ventilation

Control condition B Inclusion Criteria

• Non-ventilated patients admitted to the ICU receiving no respiratory support or oxygen therapy alone, including high flow nasal cannula

Exclusion Criteria:

• Patients expected to be extubated within 24 hours of screening for eligibility

• Patients who have already undergone a SBT at time of screening

• Patients with a previously diagnosed neuromuscular disorder

• Patients receiving long-term invasive mechanical ventilation (prior to current hospitalization)

• Patients who have required previously (during current hospitalization) a period of invasive ventilation in ICU of more than 24 hours

• Patients who have previously been enrolled in the study

• Patients for whom post-hospital follow-up may be challenging, e.g. those who reside overseas or who have no fixed address

Related Conditions & MeSH terms

• Diaphragm Injury
• Lung Injury
• Mechanical Ventilation Complication
• Respiratory Insufficiency
• Wounds and Injuries

Intervention

Other:
• Sonographic measurements
Diaphragm thickness, diaphragm tidal thickening fraction, abdominal muscle thickness, rectus femoris cross-sectional area, maximal diaphragm thickening fraction, abdominal muscle thickening fraction
• Physiological measurements
Airway occlusion pressure, maximal inspiratory pressure, muscle research council score
• Biological measurements
Skeletal troponin-I

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quality of life at home	5-level EQ-5D (EQ-5D-5L) score - The EQ-5D-5L is a validated self-reported instrument assessing quality of life at the moment questionnaire is completed. Each question is scored from 1 (no problems) to 5 (inability to perform activity) and are independently assessed.	Day 180
Primary	Quality of life at home	Montreal Cognitive Assessment (MOCA) score - MoCA is a clinician-reported measure to assess for cognitive impairments. MoCA is scored out of 30 with scores <26 indicating cognitive impairment.	Day 180
Secondary	Duration of ventilation		Until hospital discharge (up to 6 months)
Secondary	Muscle research council score	Muscle research council score, is a validated measure of muscle strength. Possible scores range from 0 (complete paralysis) to 60 (normal strength). Assessments will be made at first spontaneous breathing trial & at day 14.	Until day 14
Secondary	Airway occlusion pressure (P0.1)	P0.1 will be assessed during spontaneous breathing trial. Spontaneous breathing trials (SBT) are standard of care to assess if patients are able to be extubated from mechanical ventilation. A specific time frame cannot be provided as SBT are only conducted when care team deem the patient as capable.	First spontaneous breathing trial (within 5 minutes of onset)
Secondary	Expiratory occlusion pressure (Pocc)	Pocc will be assessed during spontaneous breathing trial. Spontaneous breathing trials (SBT) are standard of care to assess if patients are able to be extubated from mechanical ventilation. A specific time frame cannot be provided as SBT are only conducted when care team deem the patient as capable.	First spontaneous breathing trial (within 5 minutes of onset)
Secondary	Maximal inspiratory pressure (MIP)	MIP will be assessed during spontaneous breathing trial. Spontaneous breathing trials (SBT) are standard of care to assess if patients are able to be extubated from mechanical ventilation. A specific time frame cannot be provided as SBT are only conducted when care team deem the patient as capable.	First spontaneous breathing trial within 30 minutes of onset
Secondary	Days alive and at home at 180 days post ICU discharge		Day 180
Secondary	Changes in abdominal muscle thickening fraction during cough	Abdominal muscle thickening fraction during cough will be assessed by ultrasound during SBT when care team deems patient capable and safe to do so, as such a specific time frame for SBT cannot be provided. Additionally abdominal muscle thickening fraction will be assessed at ICU discharge. A specific time frame cannot be provided as ICU discharge will vary between patients.	At first spontaneous breathing trial within 30 minutes of onset and at ICU discharge, an average of 7 days
Secondary	Maximal diaphragm thickening fraction	Maximal diaphragm thickening fraction will be assessed by ultrasound during SBT when care team deems patient capable and safe to do so, as such a specific time frame for SBT cannot be provided. Additionally abdominal muscle thickening fraction will be assessed at ICU discharge. A specific time frame cannot be provided as ICU discharge will vary between patients.	At first spontaneous breathing trial within 30 minutes of onset and at ICU discharge, an average of 7 days
Secondary	Changes in resting abdominal muscle thickening	Diaphragm ultrasound to measure thickening of abdominal muscles during resting tidal breathing.	Until Day 14
Secondary	Changes in resting thickening fraction	Diaphragm ultrasound to measure thickening fraction during resting tidal breathing.	Until Day 14