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PReventing EXtubation FAILure Related to Cough (PREXFAIL)

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ClinicalTrials.gov Identifier: NCT03562000
Recruitment Status : Not yet recruiting
First Posted : June 19, 2018
Last Update Posted : June 18, 2019
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date  ICMJE June 8, 2018
First Posted Date  ICMJE June 19, 2018
Last Update Posted Date June 18, 2019
Estimated Study Start Date  ICMJE July 1, 2019
Estimated Primary Completion Date July 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
Re-intubation rate, including every cause [ Time Frame: 48 hours ]
Re-intubation rate, including every causes evaluated at 48h (expressed as a percentage). The causes could including include cardiac arrest, acute haemodynamic failure, acute neurological failure (agitation or increased loss of wakefulness compared to the initial state), acute respiratory failure (clinical signs of ARF, namely increased breathing rate > 40/min, pH < 7.35, SpO2 < 92% during > 5 min using a Fi = 1, repeated desaturations, intolerance to Non Invasive Ventilation). Any death before 48h is considered as an extubation failure, whatever its cause.
Original Primary Outcome Measures  ICMJE
 (submitted: June 8, 2018)
Re-intubation rate, including every cause [ Time Frame: 48 hours ]
Re-intubation rate, including every causes evaluated at 48h and including any cardiac arrest, acute haemodynamic failure, acute neurological failure (agitation or increased loss of wakefulness compared to the initial state), acute respiratory failure (clinical signs of ARF, namely increased breathing rate > 40/min, pH < 7.35, SpO2 < 92% during > 5 min using a Fi = 1, repeated desaturations, intolerance to Non Invasive Ventilation). Any death before 48h is considered as an extubation failure, whatever its cause.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
  • Evaluation of the efficacy on mortality. [ Time Frame: 90 days or the duration of the hospitalisation. ]
    Assessing the mortality rate at 90 days post-randomisation/extubation and assessing complementarily the mortality rate at the ICU discharge and at the hospital discharge.
  • Evaluation of the efficiency on ICU care management [ Time Frame: 90 days or the duration of the hospitalisation. ]
    Assessing the re-intubation rate at 7 days post-randomisation/extubation and assessing the overall extubation failure during the ICU hospitalisation (as a composite of the re-intubation rate and the tracheostomy rate). Describing the causes of re-intubation (related to bronchial overload, opposed to other causes such as acute pulmonary oedema, which will be analysed separately) and the post-extubation nosocomial pneumonia leading to a curative antibiotherapy in ICU. Assessing at 90 days post-randomisation/extubation the number of days without invasive respiratory support and without any respiratory support. Defining qualitatively the respiratory function at 90 days post-randomisation/extubation (dyspnoea, persistent bronchial overload, continuing physiotherapy). Describing the duration of: standard oxygenation, NIV after the first extubation, invasive ventilation after the first extubation, ICU stay and in-hospital stay.
  • Assessment of the clinical and biological efficacy of the cough assistance [ Time Frame: 24 hours ]
    Comparing between the two groups: i) a semi-quantitatively evaluation of the bronchial overload before extubation and after the first physiotherapy treatment post extubation (with and without intervention, respectively) using a convenient "Bronchial Overload scale" build on a Likert basis defined between 1 (low bronchial overload with a better excepted extubation outcome) to 5 (high bronchial overload with a worse excepted extubation outcome) and assessed by an third party; ii) the difference of arterial blood gas (with and without mechanical intervention on cough, respectively).
  • Assessment of the clinical tolerance of the intervention [ Time Frame: 7 days ]
    Assessing the number of treatment cessation due to tolerance issue and defined as Adverse Effects and Serious Adverse Effects. Describing the haemodynamic profiles of patient in both groups during the physiotherapy (with and without mechanical intervention on cough, respectively). Assessing the number of mechanical treatment failure requiring a change of the physiotherapy technique.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2018)
  • Evaluation of the efficacy on mortality. [ Time Frame: 90 days or the duration of the hospitalisation. ]
    Assessing the mortality rate at 90 days post-randomisation/extubation and assessing complementarily the mortality rate at the ICU discharge and at the hospital discharge.
  • Evaluation of the efficiency on ICU care management [ Time Frame: 90 days or the duration of the hospitalisation. ]
    Assessing the re-intubation rate at 7 days post-randomisation/extubation and assessing the overall extubation failure during the ICU hospitalisation (as a composite of the re-intubation rate and the tracheostomy rate). Describing the causes of re-intubation (related to bronchial overload, opposed to other causes such as acute pulmonary oedema, which will be analysed separately) and the post-extubation nosocomial pneumonia leading to a curative antibiotherapy in ICU. Assessing at 90 days post-randomisation/extubation the number of days without invasive respiratory support and without any respiratory support. Defining qualitatively the respiratory function at 90 days post-randomisation/extubation (dyspnoea, persistent bronchial overload, continuing physiotherapy). Describing the duration of: standard oxygenation, NIV after the first extubation, invasive ventilation after the first extubation, ICU stay and in-hospital stay.
  • Assessment of the clinical and biological efficacy of the cough assistance [ Time Frame: 24 hours ]
    Comparing between the two groups: i) a semi-quantitatively evaluation of the bronchial overload before extubation and after the first physiotherapy treatment post extubation (with and without intervention, respectively) using a convenient Likert scale between 1 to 5 and assessed by an third party; ii) the difference of arterial blood gas (with and without mechanical intervention on cough, respectively).
  • Assessment of the clinical tolerance of the intervention [ Time Frame: 7 days ]
    Assessing the number of treatment cessation due to tolerance issue and defined as Adverse Effects and Serious Adverse Effects. Describing the haemodynamic profiles of patient in both groups during the physiotherapy (with and without mechanical intervention on cough, respectively). Assessing the number of mechanical treatment failure requiring a change of the physiotherapy technique.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PReventing EXtubation FAILure Related to Cough
Official Title  ICMJE PReventing EXtubation FAILure by Cough Assistance and NIV in a Population Selected on Cough Peak Flow
Brief Summary

After the admission in ICU, most patients have to be intubated in order to control haematosis in case of acute respiratory failure, to reduce the metabolic crisis during severe haemodynamic shock, or to protect upper airways in case of impairment of consciousness. After the initial phase of etiological treatment, as soon as the patients no more required the intubation, weanibility has to be checked (thanks to a weaning trial with or without pressure support) before the separation attempt is decided on an evaluation of the overall extubability, based in particular on a subjective assessment of cough strength. The cases of re-intubation can be related to several factors such as: i) a ventilatory insufficiency indicating an imbalance between the muscular pomp function and the mechanical constraint of the chest; ii) an acute cardiogenic oedema; iii) an obstruction of the superior airways, possibly due to an imbalance between the bronchial overload and the cough efficacy.

Preventing extubation failure should avoid exposing such patients to an over-risk of morbidity and mortality due to the consequences of a prolonged invasive ventilation. This prevention can be implemented thanks to an early detection of the patients the most at risk and then a coherent intervention to manage of each risk factor involved. For example, the inspiratory insufficiency can be fixed by the use of Non-Invasive Ventilation (NIV), as proposed for patients developing a final hypercapnia at the end of the weanibility test.

Several studies have been conducted to improve the prediction of extubation failure. As this is notably influenced by the cough efficacy before extubation, it has been proposed to assess the peak flow expiratory during voluntary cough. The Cough Peak Flow could for example replaced some semi-quantitative measures of cough strength associated to a low reproducibility. The most validated threshold for a weak cough is < 60 L/min and it has recently been demonstrated that it remained valuable when directly assessed using the built-in ventilator flow-meter.

In the meantime, new devices of mechanical cough assistance have been developed and are frequently used for patients presenting a chronic neuro-muscular disease affecting their ability to spontaneously clear their airways from an inappropriate bronchial overload. However, the interest of such devices for a systematic use after extubation has not been validated with a sufficient level of evidence to be recommended, in particular because of the bias of the single randomised monocentric study.

The main objective of the study consists in demonstrating in an open multicentre randomised study (focused on the patients with an objective low cough strength) the superiority of a systematic strategy combining mechanical cough assistance and non-invasive ventilation on standard care (manual post-extubation physiotherapy and NIV for restrictive indications) to reduce the re-intubation rate at 48h.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Patients Intubated in ICU Before Extubation
Intervention  ICMJE
  • Device: Cough Assistance and Systematic Non-Invasive Ventilation

    A standardised bundle of intervention will be tested using the combination of two medical devices previously used in daily clinical practice but without guideline and objective selection criteria, namely:

    1. A mechanical cough assistance technic using the Cough Assist device (Model E70® by Philips Respironics, Carlsbad, CA, USA) before extubation then after extubation then 3 times a day (with possible additional treatment on demand) during 7 days maximum (with a possible cessation if the patient has strictly no bronchial overload during three consecutive physiotherapy sessions)
    2. A systematic Non-Invasive ventilation during 24h minimum to indirectly improve the clearance of bronchial overload and to reduce the overall risk of re-intubation related a relative hypoventilation associated to the weak cough.
  • Procedure: control group using the current gold standard of care after extubation, namely the manual drainage by a physiotherapist and the consensual use of Non-invasive ventilation
    1. After extubation, the physiotherapy will be managed according to standard care and cough assistance will be only manual. The use of a dedicated cough assistance device will be allowed if the bronchial overload clearance is repeatedly insufficient according to the physiotherapist in charge.
    2. Non-invasive ventilation will not be systematic and only used in case of pre-defined condition, such as: age > 65 years-old, BMI > 30, Chronic cardiac failure, COPD, hypercapnia at the end of the weaning trial, post-operative admissions after abdominal and thoracic surgery.
Study Arms  ICMJE
  • Experimental: Intervention group on cough and ventilation assistance
    Mechanical cough assistance during physiotherapy post-extubation in ICU and systematic indication of NIV.
    Intervention: Device: Cough Assistance and Systematic Non-Invasive Ventilation
  • Control group on cough and ventilation assistance
    Control group of extubated patients receiving the current gold standard strategy during physiotherapy after extubation in ICU and with selected indications of NIV.
    Intervention: Procedure: control group using the current gold standard of care after extubation, namely the manual drainage by a physiotherapist and the consensual use of Non-invasive ventilation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 8, 2018)
368
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2021
Estimated Primary Completion Date July 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Patients older than 18 years 2. Patients intubated for more than 24h before the extubation attempt 3. Patients able to follow simple commands and to provide a signed agreement (or, in case of neurological impairment, to confirm to a third person their will to be included in the study by their appropriate code).

    4. Patients included for their first extubation attempt after a successful weaning trial with a low pressure support (7-8 cmH2O) during 30-60 min or longer in case of neuromuscular disorders 5. No decision of care limitation 6. Informed consent form signed by the patient or by a third party attesting of the informed consent 7. Randomisation if the cough is objectively assessed as weak (CPF < 60 L/min et VT < 0.55 L). In other case, the patient with a strong cough are only included in an observational study with an outcome assessment.

Exclusion Criteria:

  • 1. Patient with tracheostomy 2. Weaning trial conducted without a pressure support technique 3. Failure of a weaning trial using a pressure support technique 4. Decision not to extubate after a successful weaning trial 5. Extubation of a patient already included after a previous extubation 6. Final extubation 7. Patients not affiliated to French health care system 8. Patients in poor medical condition (hemodynamic, respiratory instability) 9. Patients moribund or with previous decision of care limitation 10. Absence of informed consent document or patient under legal protection 11. Any clinical argument for a laryngeal oedema 12. No possibility of CPF assessment: ventilator non-adapted for assessment, no comprehension of the cough order despite a M6 response at the GCS, no measurable cough effort 13. Patient previously using a mechanical cough assistance 14. Deglutition disorders objectified or supposed (severe lesion of the brainstem), with a theoretical risk of tracheostomy 15. Contra-indication to mechanical cough assistance: pneumothorax or any lesion at risk of pneumothorax (such as costal fracture, emphysema, previous pneumothorax or other barotraumatism) 16. Contra-indication to Non-Invasive Ventilation: agitation, non-treated pneumothorax, thoracic wound, severe vomiting, active digestive haemorrhage with hematemesis, severe cranio-facial traumatism with pneumo-encephaly
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: GOBERT Florent, MD 04 72 68 12 96 florent.gobert01@chu-lyon.fr
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03562000
Other Study ID Numbers  ICMJE 69HCL18_0133
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hospices Civils de Lyon
Study Sponsor  ICMJE Hospices Civils de Lyon
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GOBERT Florent, MD Hospices Civils de Lyon
PRS Account Hospices Civils de Lyon
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP