- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03406572
Use of Nasal High Flow Oxygen During Breaks of Non-invasive Ventilation for Patients With Hypercapnic Respiratory Failure (HIGH FLOW ACRF)
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Jean-Damien Ricard
- Phone Number: +33 01.47.60.61.95
- Email: jean-damien.ricard@aphp.fr
Study Locations
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Colombes, France, 92700
- Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HFHO Group
Patients will receive a first NIV session (for 2 hours) with predefined parameters, and ABG will be performed between one and two hours of starting NIV.
NIV will be extended according to ABG result (i.e.
extended if pH < 7.30).
Switch from NIV to oxygen will require predefined criteria.
In-between each NIV session, oxygen will be delivered using a high flow nasal cannula, with a flow of 50-60L/min and a FiO2 set to reach a targeted SpO2: 88%≤SpO2 ≤ 92%.
Predefined criteria will be used to resume NIV.
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Other Names:
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Active Comparator: Standard O2 Group
NIV will be initiated based on the same criteria and with the same parameters as the HFHO group.
ABG will also be performed between one and two hours and NIV extended according to ABG result (i.e.
extended if pH < 7.30).
Switch from NIV to oxygen will require the same predefined criteria as the HFHO group.
In-between each NIV session, oxygen will be delivered using standard low flow O2 to reach the same targeted SpO2: 88% ≤SpO2 ≤ 92%.
Similar criteria will be used to resume NIV
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Standard oxygen therapy
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Number of ventilator-free days (VFDs) alive
Time Frame: At day 28 after study enrollment
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At day 28 after study enrollment
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Delay of completion of stopping rules for NIV
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Patient self-assessement of comfort during each SB period measured by Visual Analog Scale (score range 0-10, higher values represent a better outcome)
Time Frame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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After 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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Nurse assessement of comfort during each SB period measured by Likert scale (score range1-5; higher values represent a better outcome)
Time Frame: After 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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After 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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Hospital length of stay
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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All cause mortality
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Proportion of patients with facial skin erythema and/or ulceration
Time Frame: 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
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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
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Number of NIV sessions
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Duration of NIV sessions (hours)
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Number of days between the day the patient first meets criteria for NIV cessation and day 28 post-randomization
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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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)
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Proportion of patients achieving 48 consecutive hours of daytime unassisted breathing
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Proportion of patients requiring NIV resumption after 48 consecutive hours of daytime unassisted breathing
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Patient self-assessement of comfort during each NIV period measured by Visual Analog Scale (score range 0-10, higher values represent a better outcome)
Time Frame: after 1 hour of NIV, up to 28 days
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after 1 hour of NIV, up to 28 days
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Nurse assessement of comfort during each NIV period measured by Likert scale (score range1-5; higher values represent a better outcome)
Time Frame: after 1 hour of NIV, up to 28 days
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after 1 hour of NIV, up to 28 days
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Patient self-assessement of dyspnea during each SB period measured by Visual Analog Scale (range 0-10; higher values represent a worst outcome)
Time Frame: after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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Nurse assessement of dyspnea during each SB period measured by Likert scale (score range1-5; higher values represent a worst outcome)
Time Frame: after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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Patient self-assessement of dyspnea during each NIV period measured by Visual Analog Scale (range 0-10; higher values represent a worst outcome)
Time Frame: after 1 hour of NIV, up to 28 days
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after 1 hour of NIV, up to 28 days
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Nurse assessement of dyspnea during each NIV period measured by Likert scale (score range1-5; higher values represent a worst outcome)
Time Frame: after 1 hour of NIV, up to 28 days
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after 1 hour of NIV, up to 28 days
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Respiratory rate during SB periods
Time Frame: after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
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Respiratory rate during NIV periods
Time Frame: after 1 hour of NIV, up to 28 days
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after 1 hour of NIV, up to 28 days
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Proportion of patients using accessory muscles during NIV periods
Time Frame: after 1 hour of NIV, up to 28 days
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after 1 hour of NIV, up to 28 days
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Daily arterial blood gases (ABG) (in terms of pH, PaCO2 and PaO2 measured between 8-10 am).
Time Frame: up to 28 days post-randomisation
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up to 28 days post-randomisation
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Proportion of patients with premature NIV cessation (intolerance) (defined by agitation and/or mask removal, and/or patient's wish to interrupt session before)
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Proportion of patients refusing to resume NIV (despite meeting criteria)
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Proportion of patients who need secondary intubation and IMV
Time Frame: 28 days post-randomisation
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28 days post-randomisation
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Proportion of patients with nasal bridge ulceration
Time Frame: 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
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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
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Proportion of patients with eye irritation
Time Frame: 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
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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
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Proportion of patients with nasal congestion
Time Frame: 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
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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
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Proportion of patients with nasal/oral dryness
Time Frame: 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
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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
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Proportion of patients with gastric distension
Time Frame: 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
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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
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Proportion of patients with nosocomial pneumonia
Time Frame: 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
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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
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Proportion of patients with pneumothorax
Time Frame: 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
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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
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Proportion of patients with arterial hypotension
Time Frame: 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
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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
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Proportion of patients with nostril ulceration (including nasolabial angle, columella, nostril sill)
Time Frame: 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
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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
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Proportion of patients with nose bleeding
Time Frame: 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
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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
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jean-Damien Ricard, Assistance Publique - Hôpitaux de Paris
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- K160911J
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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