Clinical trial NCT03901924: Volume Support/Assist Control Mode Ventilation and Diaphragmatic Atrophy
Official title: A Phase III Randomized Trial Comparing the Effects of Volume Support and Assist Control Mode Ventilation on Ventilator-Free Days and Diaphragmatic Atrophy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mechanical Ventilation Complication
Keywords: Diaphragm Atrophy
Ventilator Induced Diaphragm Dysfunction
Mechanical Ventilation
Volume Support Mode
Assist Control Mode
Diaphragm Thickening Fraction
Intubation
Delirium
Ventilator-Free Days
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2019-04-03
Enrollment: 468
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to determine how controlled mode ventilation and support mode ventilation impact ventilator-free days and diaphragmatic atrophy.

Detailed description: Ventilator-induced diaphragmatic dysfunction (VIDD) is characterized by diaphragmatic atrophy and weakness leading to an inability to liberate from the ventilator. Patients with VIDD have increased intensive care unit and hospital length of stay, higher reintubation rates, and need for tracheostomy. There are two commonly used modes of ventilation in the ICU - controlled and support mode ventilation. Conventional practice is to initiate mechanical ventilation with controlled mode followed by a support mode to facilitate weaning and eventual extubation. However, this approach may induce irreversible diaphragmatic atrophy. Observational studies suggest that controlled ventilation is associated with higher rates of diaphragmatic atrophy than support modes of ventilation. Diaphragmatic atrophy occurs within the first 24 hours of mechanical ventilation. To date, it remains unknown whether early initiation of support mode ventilation prevents VIDD and its associated complications in comparison to controlled mode ventilation.

The investigators hypothesize that by initiating subjects on support mode ventilation, an associated increase in ventilator-free days will be seen in comparison to subjects on controlled mode ventilation. Subjects on support mode ventilation will have less diaphragmatic atrophy and weakness than subjects on controlled mode ventilation. To investigate this hypothesis,investigators are conducting a phase III randomized trial examining the effects of volume support mode versus assist control mode ventilation on ventilator-free days and rate of diaphragm atrophy.

enrolled subjects requiring mechanical ventilation will be randomized to either volume support mode or assist control mode within 24 hours of mechanical ventilation initiation. Diaphragm thickness will be measured by ultrasound daily and subsequently diaphragm atrophy rate will be calculated in each arm. The operator acquiring ultrasound images will be blinded to the ventilator mode that the subject was randomized to. Subjects in the study will follow standard ICU sedation awakening trials and spontaneous breathing trials. The medical team in charge of the subject will determine when the subject will be liberated from the ventilator.

There will be up to a 24 hour period from initiation of standard, non-study mechanical ventilation during which the subject can be consented and enrolled. This will allow the research team time to contact the subject and/or family in order to obtain informed consent. Once randomized, all subjects will be initiated on study mode of ventilation. The medical team will direct other aspects of care.

The phase III trial will be powered to determine if there is a statistically significant difference in rate of diaphragm atrophy and ventilator-free days between volume support mode and assist control mode.

Eligibility criteria: Inclusion Criteria:

subjects \> 18 years of age that have been intubated and mechanically ventilated for \< 36 hours at the time of screening will be eligible for enrollment

Exclusion Criteria:

1. pregnancy
2. cardiopulmonary arrest
3. history of diaphragmatic paralysis or neuromuscular disease
4. chronic obstructive pulmonary disease (COPD) or asthma exacerbation with evidence of auto-PEEPing requiring intubation
5. neuromuscular blockade
6. expectation to be liberated from ventilator in \< 24 hours
7. history of mechanical ventilation in the last 6 months
8. presence of tracheostomy
9. high cervical spine injury

Primary outcomes:
measure: Ventilator-Free Days
timeFrame: 28 days
Secondary outcomes:
measure: Rate of Diaphragm Atrophy
timeFrame: Through study completion, an average of 28 days
Other outcomes:
measure: Noninvasive Measurements of Diaphragm Inspiratory Strength 3.+ 9+ Noninvasive Measurements of Diaphragm Function
timeFrame: Through study completion, an average of 28 days
measure: Noninvasive Measurements of Diaphragm Expiratory Strength
timeFrame: Through study completion, an average of 28 days
measure: Diaphragm Thickening Fraction
timeFrame: Through study completion, an average of 28 days
measure: Duration of Mechanical Ventilation
timeFrame: 28 days
measure: Frequency of Ventilator-Related Complications
timeFrame: Through study completion, an average of 28 days
measure: Readmission to ICU During Same Hospital Admission
timeFrame: Through study completion, an average of 28 days
measure: Death in ICU
timeFrame: 90 days
measure: Death in Hospital
timeFrame: 90 days
measure: Discharge Destination
timeFrame: 90 days
measure: Mortality
timeFrame: 1 month, 3 months, and 12 months
Locations:
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
Study officials:
affiliation: University of Chicago
name: John P Kress, MD
role: STUDY_DIRECTOR
affiliation: University of Chicago
name: Bhakti Patel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: Roger Struble, MD
role: PRINCIPAL_INVESTIGATOR
References: