Clinical trial NCT03406572: Use of Nasal High Flow Oxygen During Breaks of Non-invasive Ventilation for Patients With Hypercapnic Respiratory Failure
Official title: Comparison of High Flow Nasal Cannula Oxygen and Conventional Oxygen Therapy on Ventilatory Support Duration During Acute-on-chronic Respiratory Failure: a Multicenter, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypercapnic Respiratory Failure
Keywords: Acute on chronic respiratory failure
High-Flow heated and humidified nasal oxygen therapy
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Direction Générale de l'Offre de Soins
First posted: 2018-01-23
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Chronic respiratory insufficiency and COPD are the third leading cause of death worldwide. Patients decompensate at various stages of their disease and exhibit acute-on-chronic respiratory failure (ACRF), a frequent cause of ICU hospitalization for hypercapnic acute respiratory failure (ARF). Non-invasive ventilation (NIV) is the first line ventilatory treatment for hypercapnic ARF. It is applied intermittently, separated by periods of spontaneous breathing (SB) with standard oxygen (O2).

Standard O2 has drawbacks that limit the benefit of intermittent NIV in hypercapnic ARF: limited gas flow which is well below the patient's inspiratory flow rate, limited capacity and efficiency of oxygenation with non-controlled FiO2 (risk of excessive oxygen and induced hypercapnia), and cold and dry gas leading to discomfort and under-humidification of the airways and tracheobronchial secretions. Benefits in terms of work of breathing and CO2 removal resulting from PEEP and pressure support applied during NIV periods could be rapidly lost during standard O2.

Recently, use of high-flow heated and humidified nasal oxygen therapy (HFHO) has gained enthusiasm among intensivists to manage ARF. HFHO delivers high flows (up to 60L/min, that generate moderate PEEP) of heated and humidified oxygen at a controlled and adjustable FiO2 (21 to 100%) that rapidly improve respiratory distress symptoms, oxygenation, respiratory comfort and outcome of patients with hypoxemic ARF.

These unique features of HFHO could overcome some of the drawbacks of standard O2 during SB periods in hypercapnic ARF. Indeed, PEEP effect, washout of nasopharyngeal dead-space limiting CO2 re-breathing and inspired gas conditioning preserving adequate mucosal function and secretion removal, could potentially contribute to decrease airways resistance, intrinsic PEEP and work of breathing, while improving patient comfort. Investigators aim to determine if the use of HFHO, as compared to standard O2, increases the number of ventilator-free days (VFDs) and alive at day 28 in patients with hypercapnic ARF admitted in an ICU, an intermediate care, or a respiratory care unit, and requiring NIV.

Detailed description: In both groups, treatment will start with a first NIV session of 2 hours, with arterial blood gas measurement between one hour and two hours after initiating the NIV session. The NIV will be extended for those patients with a pH \< 7.30. In both groups, patients will be assessed for their tolerance of NIV and their ability to switch to spontaneous breathing every hour +/- 30 min, except during sleep (10 pm-8 am); they will be assessed for their tolerance of spontaneous breathing and for the need of resumption of NIV every 2 hours+/- 30 min and every 4 +/- 1 hours thereafter. To ensure the consistency of indications of NIV and invasive mechanical ventilation (IMV) across centers and reduce potential bias, NIV and IMV will be initiated and stopped in the same way in the two groups, using predefined criteria.

* Inclusion (day 0): informed consent, randomisation (HFHO group/standard O2 group), NIV initiation (for 2 hours), clinical and paraclinical exam including ABG, data collection
* Follow-up (day 1 to day 28) : NIV, clinical exam, ABG, data collection

Eligibility criteria: Inclusion criteria

* Adult patients aged 18 or above, admitted to an ICU, an intermediate care or a respiratory care unit;
* Chronic respiratory disease previously documented or strongly suspected on clinical, radiological and blood gazes data and pulmonary function tests, in connection with an obstructive respiratory disease (COPD, emphysema, overlap-syndrome (COPD + obstructive sleep apnoea) or mixed (bronchiectasis, obesity-hypoventilation syndrome))
* Patients requiring NIV for hypercapnic ARF (whatever the precipitating cause) i.e. with clinical signs of moderate to severe respiratory distress : dyspnea and /or respiratory rate \> 25/min and/or use of accessory respiratory muscles and/or paradoxical abdominal motion and/or signs of respiratory encephalopathy (sleepiness, asterixis, confusion); and respiratory acidosis on arterial blood gases, defined by pH\<7.35 and PaCO2 \> 45 mmHg despite the careful supply of oxygen and appropriate therapy that may include bronchodilators, corticosteroids and antibiotics

Exclusion criteria

* Contraindications to NIV;
* Purely restrictive lung disease (thoracic deformity, neuro-muscular pathology) and pure obstructive sleep apnoea (without spirometric disturbance or daytime gas anomaly)
* Immediate need for intubation (respiratory or cardiac arrest);
* Persistent hemodynamic instability (use of vasopressors for \> 1 hour);
* Multiple organ failure (score SOFA\>6);
* NIV treatement for \>3 consecutive hours (without any interruption) before admission to ICU, intermediate care, or respiratory care unit and before randomization;
* Anticipated difficulties to conduct NIV (facial trauma or deformation, edentulous patient);
* End stage chronic respiratory insufficiency (defined as use of NIV at home or CPAP treatment at home and life expectancy below 6 month);
* Non-treated pneumothorax;
* Impossibility to perform subjective assessment of dyspnea and comfort (cognitive impairment);
* Patient under guardianship or trusteeship;
* Pregnancy/breastfeeding;
* Decision to withhold or to withdraw life-sustaining treatments (including intubation)
* Moribund state
* Current participation in another clinical trial with an endpoint related to NIV.
* No affiliation to social security (beneficial or assignee);
* Refusal to participate to the study (patient or legal representative or family member or close relative if present

Primary outcomes:
measure: Number of ventilator-free days (VFDs) alive
timeFrame: At day 28 after study enrollment
Secondary outcomes:
measure: Delay of completion of stopping rules for NIV
timeFrame: 28 days post-randomisation
measure: Patient self-assessement of comfort during each SB period measured by Visual Analog Scale (score range 0-10, higher values represent a better outcome)
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
measure: Nurse assessement of comfort during each SB period measured by Likert scale (score range1-5; higher values represent a better outcome)
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
measure: Hospital length of stay
timeFrame: 28 days post-randomisation
measure: All cause mortality
timeFrame: 28 days post-randomisation
measure: Proportion of patients with facial skin erythema and/or ulceration
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Number of NIV sessions
timeFrame: 28 days post-randomisation
measure: Duration of NIV sessions (hours)
timeFrame: 28 days post-randomisation
measure: Number of days between the day the patient first meets criteria for NIV cessation and day 28 post-randomization
timeFrame: 28 days post-randomisation
measure: Number of days between the day of initially achieving unassisted ventilation and day 28 post-randomization (i.e. after having successfully spent 48 consecutive hours of unassisted breathing)
timeFrame: 28 days post-randomisation
measure: Proportion of patients achieving 48 consecutive hours of daytime unassisted breathing
timeFrame: 28 days post-randomisation
measure: Proportion of patients requiring NIV resumption after 48 consecutive hours of daytime unassisted breathing
timeFrame: 28 days post-randomisation
measure: Patient self-assessement of comfort during each NIV period measured by Visual Analog Scale (score range 0-10, higher values represent a better outcome)
timeFrame: after 1 hour of NIV, up to 28 days
measure: Nurse assessement of comfort during each NIV period measured by Likert scale (score range1-5; higher values represent a better outcome)
timeFrame: after 1 hour of NIV, up to 28 days
measure: Patient self-assessement of dyspnea during each SB period measured by Visual Analog Scale (range 0-10; higher values represent a worst outcome)
timeFrame: after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
measure: Nurse assessement of dyspnea during each SB period measured by Likert scale (score range1-5; higher values represent a worst outcome)
timeFrame: after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
measure: Patient self-assessement of dyspnea during each NIV period measured by Visual Analog Scale (range 0-10; higher values represent a worst outcome)
timeFrame: after 1 hour of NIV, up to 28 days
measure: Nurse assessement of dyspnea during each NIV period measured by Likert scale (score range1-5; higher values represent a worst outcome)
timeFrame: after 1 hour of NIV, up to 28 days
measure: Respiratory rate during SB periods
timeFrame: after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
measure: Respiratory rate during NIV periods
timeFrame: after 1 hour of NIV, up to 28 days
measure: Proportion of patients using accessory muscles during NIV periods
timeFrame: after 1 hour of NIV, up to 28 days
measure: Daily arterial blood gases (ABG) (in terms of pH, PaCO2 and PaO2 measured between 8-10 am).
timeFrame: up to 28 days post-randomisation
measure: Proportion of patients with premature NIV cessation (intolerance) (defined by agitation and/or mask removal, and/or patient's wish to interrupt session before)
timeFrame: 28 days post-randomisation
measure: Proportion of patients refusing to resume NIV (despite meeting criteria)
timeFrame: 28 days post-randomisation
measure: Proportion of patients who need secondary intubation and IMV
timeFrame: 28 days post-randomisation
measure: Proportion of patients with nasal bridge ulceration
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Proportion of patients with eye irritation
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Proportion of patients with nasal congestion
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Proportion of patients with nasal/oral dryness
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Proportion of patients with gastric distension
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Proportion of patients with nosocomial pneumonia
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Proportion of patients with pneumothorax
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Proportion of patients with arterial hypotension
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Proportion of patients with nostril ulceration (including nasolabial angle, columella, nostril sill)
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
measure: Proportion of patients with nose bleeding
timeFrame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Other outcomes:
Locations:
city: Colombes
country: France
facility: Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean-Damien Ricard
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ricard JD, Dib F, Esposito-Farese M, Messika J, Girault C; REVA network. Comparison of high flow nasal cannula oxygen and conventional oxygen therapy on ventilatory support duration during acute-on-chronic respiratory failure: study protocol of a multicentre, randomised, controlled trial. The 'HIGH-FLOW ACRF' study. BMJ Open. 2018 Sep 19;8(9):e022983. doi: 10.1136/bmjopen-2018-022983.