Volume Support/Assist Control Mode Ventilation and Diaphragmatic Atrophy

A Phase III Randomized Trial Comparing the Effects of Volume Support and Assist Control Mode Ventilation on Ventilator-Free Days and Diaphragmatic Atrophy

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

Study Overview

• Status: Recruiting
• Conditions: Mechanical Ventilation Complication
• Intervention / Treatment: Other: Volume Support Mode Mechanical Ventilation; Other: Assist Control Mode Mechanical Ventilation

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.

• Study Type: Interventional
• Enrollment (Estimated): 468
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bhakti Patel, MD; Phone Number: 773-702-0902; Email: bpatel@bsd.uchicago.edu
• Study Contact Backup: Name: Anne S Pohlman, MSN; Phone Number: 773-702-3804; Email: apohlman@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago Medical Center
      • Contact: Anne S Pohlman, MSN; Phone Number: 773-702-3804; Email: apohlman@bsd.uchicago.edu
      • Contact: Bhakti Patel, MD; Phone Number: 773-702-0902; Email: bpatel@.bsd.uchicago.edu
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Not yet recruiting
      • University of Iowa
      • Contact: Roger Struble, MD; Phone Number: 785-342-6930; Email: roger-struble@uiowa.edu
      • Contact: Boulos Nasser, MD; Phone Number: 3193546563; Email: boulos-nassar@uiowa.edu
      • Principal Investigator: Roger Struble, MD

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Volume Support Mode Mechanical Ventilation; Volume support mode ventilation is a spontaneous mode where a target goal volume is set on the ventilator. This ventilatory strategy is dependent on patients spontaneously breathing and triggering (or activating) the ventilator to support the breath. The ventilator adjusts the amount of pressure support to deliver with each breath (i.e. if the patient's tidal volume is greater than the set target volume, then the ventilator will decrease the amount of pressure support in the subsequent breath to try to achieve the goal volume and vice versa). The respiratory rate is not set in this mode of ventilation and is dependent on the patient. For patients randomized to this mode, the goal tidal volume will be set at 6 cc/kg of ideal body weight (IBW).	Other: Volume Support Mode Mechanical Ventilation; This is a spontaneous mode of mechanical ventilation that depends on the patient's efforts. A target volume (6 cc/kg of IBW), PEEP and FiO2 are set by the medical team, and the ventilator varies the inspiratory pressure support with each breath to achieve the target volume. The respiratory rate is fully dependent on the patient. Sedation while on mechanical ventilation will be set at a goal RASS of 0 to -2.
Active Comparator: Assist Control Mode Mechanical Ventilation; In assist control mode ventilation, the machine is programmed to deliver a set tidal volume and set respiratory rate. Patients can breathe over the set respiratory rate, but the volume of breath that they receive is fixed and delivered by the ventilator. For patients randomized to this mode, the tidal volume will be set at 6 cc/kg of ideal body weight (IBW).	Other: Assist Control Mode Mechanical Ventilation; This is a controlled mode of mechanical ventilation that is independent of patient's efforts. A tidal volume (6 cc/kg of IBW), respiratory rate, PEEP and FiO2 are set by the medical team. Sedation while on mechanical ventilation will be set at a goal RASS of 0 to -2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-Free Days	A Phase III Primary Outcome; Defined as days alive and free from mechanical ventilation at day 28	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Diaphragm Atrophy	Defined as percentage decline in diaphragm thickness per day	Through study completion, an average of 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Noninvasive Measurements of Diaphragm Inspiratory Strength 3.+ 9+ Noninvasive Measurements of Diaphragm Function	negative inspiratory force (nif)--measured unit cm H2O	Through study completion, an average of 28 days
Noninvasive Measurements of Diaphragm Expiratory Strength	positive expiratory force (pef)--measured unit cm H2O	Through study completion, an average of 28 days
Diaphragm Thickening Fraction	(diaphragm thickness at end expiration - diaphragm thickness at end inspiration)/diaphragm thickness at end expiration; measured by ultrasound	Through study completion, an average of 28 days
Duration of Mechanical Ventilation	Days on mechanical ventilation	28 days
Frequency of Ventilator-Related Complications	Including the Following: -reintubation; tracheostomy; mechanical ventilation > 14 days; patients with delirium	Through study completion, an average of 28 days
Readmission to ICU During Same Hospital Admission	Bivariate outcome regarding readmission to ICU--"Yes or No"	Through study completion, an average of 28 days
Death in ICU	Death that occurs while in the ICU	90 days
Death in Hospital	Death that occurs while in the Hospital	90 days
Discharge Destination	i.e. home, long term assisted care, skilled nursing facility, death	90 days
Mortality	measured at 28 days, 90 days, and 1 year	1 month, 3 months, and 12 months

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Study Director: John P Kress, MD, University of Chicago; Principal Investigator: Bhakti Patel, MD, University of Chicago; Principal Investigator: Roger Struble, MD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2019
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: February 27, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Mechanical Ventilation; Intubation; Delirium; Diaphragm Atrophy; Ventilator Induced Diaphragm Dysfunction; Volume Support Mode; Assist Control Mode; Diaphragm Thickening Fraction; Ventilator-Free Days
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy
• Other Study ID Numbers: 18-1482

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No