Re-Evaluation of Systemic Early Neuromuscular Blockade and Transthoracic Ultrasound Assessment of the Diaphragm

Study Overview
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Brief Summary
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ROSETTA is a multi-centre study evaluating the time course of diaphragm thickness and function following exposure to neuromuscular blockade or control in patients with acute respiratory distress. ROSETTA is an ancillary study to the Re-evaluation of Systemic Early Neuromuscular Blockade (ROSE) trial (NCT02509078). It is designed to (1) test the feasibility of a multi-center evaluation of the diaphragm structure and function by ultrasound during mechanical ventilation and (2) determine whether neuromuscular blockade accelerates atrophy and dysfunction of the diaphragm in patients with acute respiratory distress syndrome (ARDS).

Detailed Description
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A growing body of evidence strongly suggests that mechanical ventilation injures the respiratory muscles, particularly the diaphragm. Due to the deleterious effects of diaphragm inactivity on diaphragm function, there are important concerns about the risk of diaphragm weakness and difficult liberation from mechanical ventilation following neuromuscular blockade. Sonographic measurements of diaphragm thickness provide a potentially useful window for studying diaphragm injury and function during mechanical ventilation. Patients enrolled in the ROSE trial (randomizing patients with moderate-severe acute respiratory distress syndrome to receive neuromuscular blockade or control for 2 days) will be eligible for participation in this study. Study patients will undergo regular diaphragm ultrasound to assess diaphragm thickness and activity during the first week of the study. Diaphragm function will be assessed by ultrasound on study days 7, 14, 21, and 28. ROSETTA is designed to: Test the feasibility of a multi-center evaluation of the diaphragm structure and function by ultrasound during mechanical ventilation; Determine whether neuromuscular blockade accelerates atrophy and dysfunction of the diaphragm in patients with acute respiratory distress syndrome; and Evaluate whether patients with greater diaphragm dysfunction exhibit worse functional outcomes compared to patients without diaphragm dysfunction.

Official Title
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Re-Evaluation of Systemic Early Neuromuscular Blockade and Transthoracic Ultrasound Assessment of the Diaphragm

Conditions
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Acute Respiratory Distress Syndrome, Diaphragm Injury, Neuromuscular Blockade

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients enrolled in the ROSE PETAL trial (adult patients with moderate-severe acute respiratory distress syndrome who have received invasive mechanical ventilation for less than 5 days) Exclusion Criteria: Patients expected to be extubated within 24 hours of screening for eligibility Patients with a contraindication to chest ultrasonography (chest tubes inserted over right lower chest wall; chest wall trauma)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with moderate or severe ARDS<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study feasibility - number of participating centers | The number of centers that participate in the study | Through study completion, an average of 18 months | 
| Study feasibility - number of trained sonographers in study | The number of trained sonographers who collect measurements with ultrasound in the study | Through study completion, an average of 18 months | 
| Study feasibility - enrolment rate | Percentage of potentially eligible patients in ROSE trial who are enrolled in ROSETTA | Through study completion, an average of 18 months | 
| Study feasibility - measurement acquisition rate | Percentage of scheduled study measurements that are actually collected | Through study completion, an average of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diaphragm function | Maximal diaphragm thickening fraction | Study day 7 | 
| Changes in diaphragm thickness over time with or without neuromuscular blockade |  | First week of study |