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Non-invasive Ventilation Following Extubation (Prophylactic) to Prevent Extubation Failure in Critically Obese Patients (EXTUB-OBESE)

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ClinicalTrials.gov Identifier: NCT04014920
Recruitment Status : Recruiting
First Posted : July 10, 2019
Last Update Posted : October 7, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Montpellier

Tracking Information
First Submitted Date  ICMJE July 9, 2019
First Posted Date  ICMJE July 10, 2019
Last Update Posted Date October 7, 2019
Actual Study Start Date  ICMJE October 2, 2019
Estimated Primary Completion Date March 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2019)
The failure of the treatment, defined by a composite criteria [ Time Frame: 72 hours ]
The failure of the treatment, defined by a composite criteria combining the treatment failure, defined as reintubation for mechanical ventilation, switch to the other study treatment, or premature study-treatment discontinuation
Original Primary Outcome Measures  ICMJE
 (submitted: July 9, 2019)
The failure of the treatment, defined by a composite criteria [ Time Frame: 72h ]
The failure of the treatment, defined by a composite criteria combining the treatment failure, defined as reintubation for mechanical ventilation, switch to the other study treatment, or premature study-treatment discontinuation
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2019)
  • Incidence of acute respiratory failure [ Time Frame: up to Day 7 ]
    Occurrence of acute respiratory failure
  • Oxygenation [ Time Frame: Up to Day 7 ]
    Oxygenation will be assessed based on the lowest SpO2 value and on PaO2/FiO2 (if available)
  • Organ failure [ Time Frame: Up to Day 7 ]
    Number of organ failures as assessed by the daily SOFA score each day until Day-7
  • ICU all-cause mortality [ Time Frame: up to day 28 ]
  • Tracheal intubation rate [ Time Frame: up to day 28 ]
  • Length of stay in ICU and in hospital [ Time Frame: up to day 90 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Non-invasive Ventilation Following Extubation (Prophylactic) to Prevent Extubation Failure in Critically Obese Patients
Official Title  ICMJE Non-invasive Ventilation Following Extubation (Prophylactic) to Prevent Extubation Failure in Critically Obese Patients: a Prospective, Randomized, Multicenter Study
Brief Summary Mechanical ventilation is the first artificial support used in intensive care. After a period of invasive mechanical ventilation, patients should be separated from the ventilator (weaning period of mechanical ventilation). If weaning and extubation (removal of the tracheal tube) are successful in approximately 80 to 90% of resuscitation patients, 10 to 20% will develop acute respiratory failure (ARF) in the days following extubation. Obesity concerns 20 to 30% of resuscitation admissions in France. The pathophysiological changes in the obese patient explain the over-risk of desaturation and ARF in the post-extubation period. In order to decrease the incidence of extubation failure (need for reintubation within 48-72h post-extubation) of the most fragile patients, it is recommended in intensive care unit to prophylactically use various ventilatory support strategies and / or oxygenation, among which noninvasive ventilation (NIV) and oxygen therapy, which can be administered in two ways: High-Flow Humidified Nasal Oxygen Therapy (HFNO) or standard oxygen therapy. These strategies have never been compared in the obese post-extubation critically ill patient. Our hypothesis is that NIV is superior to oxygen to prevent the development of ARF in obese extubated patients in intensive care unit.
Detailed Description

Mechanical ventilation is the first artificial support used in intensive care unit (ICU). After a period of invasive mechanical ventilation, patients should be separated from the ventilator (weaning period of mechanical ventilation). If weaning and extubation (removal of the tracheal intubation tube) is successful in approximately 80 to 90% of resuscitation patients, 10 to 20% will develop acute respiratory failure (ARF) in the days following extubation . This incidence is higher in the patients most fragile in the respiratory field (obese patients, chronic obstructive pulmonary disease (COPD), elderly, heart failure, postoperative cardio-thoracic and / or abdominal surgery ...) . The management of post-extubation ARF consists of etiological treatment associated with ventilatory support which usually requires the use of new endotracheal intubation to deliver "invasive" artificial ventilation. This invasive ventilation is responsible for excess morbidity and excess mortality . Therefore, it is fundamental for the physician to prevent by all means the occurrence of ARF post-extubation. One of the most important causes of extubation failure is the imbalance between the burden imposed on the respiratory system and its ability to overcome it, leading to gas exchange abnormalities, namely hypoxia and hypercapnia. Ensuring adequate oxygenation is therefore essential after extubation. In ICU, oxygen therapy is commonly used to improve and provide adequate oxygenation .

Obesity, a major public health problem in the industrialized countries, concerns 10 to 20% of resuscitation admissions in France. It is associated with excess morbidity and longer mechanical ventilation time compared to the general population. Effect on mortality is controversial , some studies suggesting a protective or neutral effect of obesity , named "obesity paradox" . At the ventilatory level, several pathophysiological changes are combined and contribute to an increase in the incidence of respiratory complications . Pulmonary volumes are amputated, the Body Mass Index (BMI) being negatively correlated with the functional residual capacity and vital capacity. The compliance of the respiratory system is reduced by the weight of the chest wall. Decreased compliance and increased airway resistance lead to increased respiratory muscle work. All of these pathophysiological changes in the obese patient explain the over-risk of desaturation and ARF in the post-extubation period. In addition to the intrinsic risk factors associated with obesity, the post-extubation period is marked by numerous risk factors for the development of ARF and extubation failure.

However, the exploration of different modern modalities of adequate post-extubation oxygen therapy in obese resuscitation patients to prevent the occurrence of extubation failure or post-extubation ARF has never been studied.

For over 20 years, Non-Invasive Ventilation (NIV) has been an essential modality in the prevention ("preventive NIV") and management ("curative NIV") of respiratory failure in ICU. The advantages of this ventilation modality are: respect for airway defense mechanisms (speech and cough maintenance), elimination of laryngeal and tracheal trauma induced by an intubation tube, improved comfort, reduction of the risk of bronchopulmonary nosocomial infection .

An alternative to NIV is the simple administration of oxygen. Two devices delivering low oxygen flows are commonly used for oxygen therapy after extubation: the Venturi mask and the nasal cannulas. The nasal cannulas are preferred by patients and less likely to be removed, but they can cause discomfort due to dryness of nasal mucosa when oxygen flows greater than 4 L/min are used. The Venturi mask delivers predetermined oxygen concentrations ranging from 24 to 60%, but the mask is generally less comfortable than the nasal cannula and more likely to be displaced or removed . In clinical practice, the Venturi mask is more frequently used after extubation because critically ill patients breathe preferentially through an open mouth rather than the nose.

More recently, a new oxygen therapy device has been marketed. This device (Optiflow®, Fisher & Paykel, New Zealand) of High Flow Nasal Humidified Oxygen Therapy (HFNO) is able to deliver oxygen humidified by nasal cannulas. This system has several theoretical advantages: high flow rates reduce the dilution of inhaled oxygen and allow precise distribution of FiO2 throughout the inspiratory phase by adapting the peak flow rate to the patient. The high oxygen flow can also have a washing effect on the dead space of the nasopharynx. In addition, a flow-dependent effect helps to generate a continuous positive end-expiratory pressure (PEEP) , related to an air entrainment mechanism, which has been documented in healthy volunteers and COPD patients. Finally, the use of a high level of humidity could prevent alterations of the ciliated epithelium of the respiratory tract, maintain the activity of the muco-ciliary system, and facilitate the elimination of secretions . In a study in non-obese patients, HFNO was shown to improve oxygenation compared to the Venturi mask, while reducing respiratory rate, PaCO2 and discomfort in patients receiving oxygen therapy after extubation. These positive effects of HFNO were associated with less interface displacement and less oxygen desaturations than the Venturi mask. A secondary result was that the need for reintubation at 48 h was lower with HFNO than with the Venturi mask (4% vs 21%).

In summary, in order to decrease the incidence of extubation failure (need for reintubation within 48-72h post-extubation) of the most fragile patients (including obese patients), it is recommended in intensive care unit to prophylactically use various ventilatory support strategies and / or oxygenation, among which:

  • NIV which allows to deliver an established level of oxygen delivered via ventilatory assistance using two levels of pressure (inspiratory aid + positive expiratory pressure), but intermittently, with duration of sessions dependent on the tolerance of the patient.
  • Oxygen therapy, which can be administered in two ways: HFNO or standard oxygen therapy.

3.2 Knowledge gap and research hypothesis In an observational study of 124 patients, EL Sohl et al. compared NIV to standard oxygen to prevent extubation failure, and showed a 16% absolute risk reduction of ARF using NIV compared to standard oxygen following extubation. In 155 post cardiac surgery obese patients, Corley et al. compared HFNO and standard oxygen to prevent extubation failure, without showing any difference.

However, none of these studies compared simultaneously the most recent devices available: NIV, HFNO and standard oxygen, nor their association. HFNO is now often used, and the PEP issued by HFNO is much lower than that issued by the NIV. The opening of the cells and the probable maintenance of the residual functional capacity is less when using HFNO than NIV. Thus, the two oxygenation methods (NIV and HFNO) appear complementary in case of ARF following extubation in obese patients. The benefit of NIV +/- HFNO compared to oxygen (standard oxygen or HFNO) to improve the quality of post-extubation oxygenation of overall ICU obese patients has never been studied.

In this multicenter, randomized, controlled, interventional study in mechanically ventilated obese critically ill patients, we will test the hypothesis that NIV (associated to HFNO or standard oxygen) is superior to oxygen (HFNO or standard oxygen) to prevent the development of ARF in obese extubated patients in intensive care unit.

3.3 Originality and innovative aspects of the study NIV has proven effective in small observational studies in preventing ARF following extubation of obese patients, in ICU or postoperative setting. The control group was standard oxygen therapy, which was the standard of care a few years ago. Nowadays, HFNO is more and more used, and has proven to be non-inferior to NIV in ARF patients following cardiothoracic surgery and in high risk patients after extubation in the ICU. To date no prospective randomized study has compared NIV (alternated with HFNO or standard oxygen) with oxygen therapy (HFNO or standard oxygen) to prevent extubation failure in obese patients. This study would be the first to compare the association of the most recent advances in term of oxygenation and lung recruitment in critically ill patients: NIV, HFNO and standard oxygen.

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
  • Obesity
  • Ventilation
  • Intensive Care Unit
Intervention  ICMJE
  • Device: Oxygen group
    The control group will receive oxygen (first randomization), HFNO oxygen or standard oxygen (second randomization)
  • Device: NIV Group
    The experimental group will receive NIV (first randomization) alternated with HFNO or standard oxygen (second randomization)
Study Arms  ICMJE
  • Active Comparator: Oxygen Group
    Patient will receive standard oxygenotherapy
    Intervention: Device: Oxygen group
  • Experimental: NIV Group
    Patient will receive non invasive ventilation
    Intervention: Device: NIV Group
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 9, 2019)
1000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2024
Estimated Primary Completion Date March 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult (age ≥ 18 years)
  • Subjects must be covered by public health insurance
  • Obese patients defined by a body mass index ≥ 30 kg/m²
  • Extubation after a length of mechanical ventilation >= 6 hours
  • Written informed consent from the patient or proxy (if present) before inclusion or once possible when patient has been included in a context of emergency.

Exclusion Criteria:

  • Refusal of study participation or to pursue the study by the patient
  • Hypercapnia with a formal indication for NIV (PaCO2 ≥ 50 mmHg, formal indication for NIV)
  • Isolated cardiogenic pulmonary edema (formal indication for NIV). Patients with pulmonary edema associated with another ARF etiology can be included.
  • Pregnancy or breastfeeding
  • Anatomical factors precluding the use of NIV and/or HFNO
  • Absence of coverage by the French statutory healthcare insurance system
  • Patients with tracheostomy
  • Patients with CPAP for obstructive apnea syndrome
  • Patients with decision of no-reintubate (limitation)
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: Audrey DE JONG 0033467337271 a-de_jong@chu-montpellier.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04014920
Other Study ID Numbers  ICMJE 7770
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Supporting Materials: Clinical Study Report (CSR)
Time Frame: 12 months after the main publication
Access Criteria: Data are provided to qualified investigators free of charge. Required documents to request data include a summary of the research plan, request form, and IRB review. Dataset will be shared after careful examination by the study board of investigators.
Responsible Party University Hospital, Montpellier
Study Sponsor  ICMJE University Hospital, Montpellier
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University Hospital, Montpellier
Verification Date October 2019

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