Multicenter, Multinational, Clinical Trial of the Performance of RESPINOR DXT to Identify Patients at Increased Risk of Weaning Failure

Study Overview
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Brief Summary
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The study will be a multicenter, multinational, prospective single arm blinded study to validate DXT's performance to identify patients at increased risk of weaning failure during the spontaneous breathing trial (SBT). Continuous diaphragmatic excursion measurements by DXT will be conducted during the patients' first SBT. The recording shall be initiated 15 minutes prior to the first SBT and will end 15 minutes post SBT. All patients on mechanical ventilation in the ICU meeting the eligibility criteria shall undergo a daily screen for weaning readiness. If any of the components of the daily screen is not met, the patient will not undergo a SBT that day and continued to be screened daily. Patients passing daily screening criteria shall automatically receive an SBT. The SBT shall last for 30-120 minutes and be performed on continuous positive airway pressure up to 5 cm H2O and pressure support up to 7 cm H2O. The SBT shall be terminated and mechanical ventilation reinstituted at the original settings if the patient meets any of the SBT failure criteria. A trial is considered successful and physicians will be asked to approve extubation when the patient can breathe spontaneously for the whole trial. Patients shall be continued to be screened daily until extubation, 21 days after enrolment, performance of tracheostomy, death, or withdrawal of care. All patients shall be followed until hospital discharge or death.

Official Title
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Multicenter, Multinational, Clinical Trial of the Performance of RESPINOR DXT to Identify Patients at Increased Risk of Weaning Failure

Conditions
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Respiratory Failure

Intervention / Treatment
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* Device: RESPINOR DXT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients willing and able to give informed consent (either themselves or next of kin) Have undergone invasive mechanical ventilation > 24 hours Ready to wean according to criteria (from the sixth international consensus conference on intensive care medicine): Adequate cough Absence of excessive tracheobronchial secretion Resolution of disease acute phase for which the patient was intubated Clinical stability, defined as stable cardiovascular status (i.e. fC < 140 beats·min-1, systolic BP 90-160 mmHg, no or minimal vasopressors) and stable metabolic status Adequate oxygenation, defined as SaO2 > 90% on < FIO2 0.4 (or PaO2/FIO2 > 150 mmHg) and PEEP < 8 cmH2O Adequate pulmonary function, i.e. fR < 35 breaths·min-1 Adequate mentation, defined as no sedation or adequate mentation on sedation (or stable neurologic patient), i.e., patient awake, calm and responsive to simple orders (squeeze hand, knock the head, close the eyes), no agitation. Exclusion Criteria: Not registered with a social security system nor entitled to be Central or spinal neurological injury involving central ventilatory control Presence of a neuromuscular disease involving respiratory muscles Use of muscle-paralyzing agents within 24h before the study, except if given for intubation Known paralysis of a hemidiaphragm or suspicion of paralysis of a hemidiaphragm, defined by the radiographic evidence of elevation of a dome > 2.5 cm compared to the contralateral dome Tracheostomy Body mass index >35 kg/m2 Patient with therapeutic limitation, i.e. reduced expectancy to survive Pregnant woman or protected adult

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Weaning failure<br>Defined as the failure to pass a spontaneous breathing trial or the need for reintubation or death within 48 hours | Device: RESPINOR DXT<br>* Blinded, continuous diaphragmatic excursion measurements by DXT will be conducted during the patients' first SBT. The recording shall be initiated 15 minutes prior to the first SBT and will end 15 minutes post SBT.<br>|
| Weaning success<br>Defined as a successful spontaneous breathing trial and is not reintubated or dies in the first 48 hours after extubation. | Device: RESPINOR DXT<br>* Blinded, continuous diaphragmatic excursion measurements by DXT will be conducted during the patients' first SBT. The recording shall be initiated 15 minutes prior to the first SBT and will end 15 minutes post SBT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the rate of weaning failure between patients with a DE < 1.1 cm compared to those with a DE > 1.1 cm. | Median DE measurements taken during the second minute of the SBT will be used in the analysis. The hypothesis is that patients with DE < 1.1 cm will have significantly higher rate of weaning failure compared to those with a DE > 1.1 cm. The relative risk (RR) statistic will be used to assess the null hypothesis of equality. | Second minute of the first SBT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the rate of weaning failure with reintubation failure 72 hours and 7 days after extubation between patients with a DE <1.1 cm compared to those with a DE >1.1 cm. | Median DE measurements taken during the second minute of the SBT will be used in the analysis. The hypothesis is that patients with DE < 1.1 cm will have significantly higher rate of weaning failure compared to those with a DE > 1.1 cm. The relative risk (RR) statistic will be used to assess the null hypothesis of equality. | Second minute of the first SBT | 
| Subgroup analysis on the difference in the rate of weaning failure between patients with a DE <1.1 cm compared to those with a DE >1.1 cm excluding COVID-19 patients. Similar subgroup analysis for COVID-19 patients. | Median DE measurements taken during the second minute of the SBT will be used in the analysis. The hypothesis is that patients with DE < 1.1 cm will have significantly higher rate of weaning failure compared to those with a DE > 1.1 cm. The relative risk (RR) statistic will be used to assess the null hypothesis of equality. | Second minute of the first SBT | 
| Correlation between median DE measurements taken during the second minute of the SBT and duration of mechanical ventilation prior to the first SBT, after the SBT and total mechanical ventilation time. | Plots of DE values versus MV duration will be presented, together with the estimated correlation coefficient. | Second minute of the first SBT | 
| Correlation between median DE measurements taken during the second minute of the SBT and duration of ICU stay prior to the first SBT, after the SBT and total ICU time. | Plots of DE values versus ICU duration will be presented, together with the estimated correlation coefficient. | Second minute of the first SBT | 
| Confirm thresholds for DE to predict weaning outcome during the SBT for the whole sample. | Thresholds for continuous DE will be defined by ROC curve analysis. | Second minute of the first SBT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diaphragm ultrasound, Diaphragm function, Mechanical ventilation