Multicenter, Multinational, Clinical Trial of the Performance of RESPINOR DXT to Identify Patients at Increased Risk of Weaning Failure (DE-RISK WF)

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Failure
• Intervention / Treatment: Device: RESPINOR DXT

• Study Type: Observational
• Enrollment (Actual): 193

Contacts and Locations

• Study Contact: Name: Marit Mellemseter; Phone Number: +4746810529; Email: m.mellemseter@respinor.com

Study Locations

• France
  • Angers, France
    • Centre hospitalier universitaire d'Angers
  • Lyon, France
    • Centre Hospitalier Saint Joseph Saint Luc
  • Paris, France
    • Hopital Universitaire Pitie Salpetriere
  • Cedex 12
    • Paris, Cedex 12, France, 75571
      • Hôpital Saint-Antoine
  • Chem. Des Bourrely
    • Marseille, Chem. Des Bourrely, France, 13015
      • Hôpitaux Universitaires de Marseille - AP-HM
  • Select One...
    • Montpellier, Select One..., France, 34090
      • Centre Hospitalier Universitaire de Montpellier
• Italy
  • Milan, Italy
    • Ospedale San Carlo Borromeo
• Norway
  • Oslo, Norway
    • Oslo University Hospital
  • Trondheim, Norway
    • St. Olavs University Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients under invasive mechanical ventilation in the intensive care unit

Description

Inclusion Criteria:

1. Patients willing and able to give informed consent (either themselves or next of kin)
2. Have undergone invasive mechanical ventilation > 24 hours

3. Ready to wean according to criteria (from the sixth international consensus conference on intensive care medicine):

   1. Adequate cough
   2. Absence of excessive tracheobronchial secretion
   3. Resolution of disease acute phase for which the patient was intubated
   4. 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
   5. Adequate oxygenation, defined as SaO2 > 90% on < FIO2 0.4 (or PaO2/FIO2 > 150 mmHg) and PEEP < 8 cmH2O
   6. Adequate pulmonary function, i.e. fR < 35 breaths·min-1
   7. 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:

1. Not registered with a social security system nor entitled to be
2. Central or spinal neurological injury involving central ventilatory control
3. Presence of a neuromuscular disease involving respiratory muscles
4. Use of muscle-paralyzing agents within 24h before the study, except if given for intubation
5. 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
6. Tracheostomy
7. Body mass index >35 kg/m2
8. Patient with therapeutic limitation, i.e. reduced expectancy to survive
9. Pregnant woman or protected adult

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Weaning failure; Defined as the failure to pass a spontaneous breathing trial or the need for reintubation or death within 48 hours	Device: RESPINOR DXT; 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.
Weaning success; Defined as a successful spontaneous breathing trial and is not reintubated or dies in the first 48 hours after extubation.	Device: RESPINOR DXT; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy - number of patients with overall acceptable signal quality from predefined quality criteria		First SBT
Safety - skin irritation severity	options 'no irritation', slight redness', 'red and moist tissue', 'granulation tissue', and 'infection leading to debridement'	After first SBT, when removing the sensors
Time spent on achieving good sensor placement	with options 0-5, 6-10 mins, 11-20 mins, 21-30 mins, > 30 mins	During sensor attachment before the first SBT
Safety - skin irritation frequency	Frequency of skin irritation presented in percentage for each category of skin irritation severity	After first SBT, when removing the sensors
Criteria for the Earlier Termination of the Trial - sample size calculation based on weaning failure rate	Sample size have been calculated with the basis of 4 main assumptions: proportion of weaning failure, assumed relative risk (RR), level of significance, and power. Of these, the proportion of weaning failure is independent of the outcome. Weaning failure rate was assumed to be 20%, requiring 218 patients to meet the endpoints (250 patients accounting for dropouts). If the observed weaning failure is 25%, the number of patients needed is 154 under the same assumptions. One interim assessment of study progress will be conducted. If the observed total proportion of weaning failure is 25% or above (only using the eCRF data, still blinded to the output from DXT), the Sponsor and Principal Investigator can recommend that the trial be concluded and analyzed according to the statistical analysis plan. The interim assessment will be conducted by calculating a 95% CI for the overall weaning failure. The CI will be calculated using the standard normal approximation for one sample proportions.	When a minimum of 154 subjects have been enrolled (180 when accounting for dropouts), through study completion, assessed up to 1 year

Collaborators and Investigators

• Sponsor: Respinor AS
• Collaborators: The Research Council of Norway
• Investigators: Principal Investigator: Michele Umbrello, MD, Ospedale San Carlo Borromeo; Principal Investigator: Øyvind Skraastad, MD, Oslo University Hospital; Principal Investigator: Alexandre Demoule, MD, Hopital Universitaire Pitie Salpetriere

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2021
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: January 4, 2021
• First Posted (Actual): January 6, 2021

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Mechanical ventilation; Diaphragm ultrasound; Diaphragm function
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: DXT-CS-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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