NHF vs NIV in Patients With Acute Exacerbation of COPD

Study Overview
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Brief Summary
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Although non-invasive ventilation (NIV) usage has increased significantly over time in COPD exacerbation, a great percentage of patients ( 30%) present contraindications to NIV or cannot tolerate it. Nasal high flow (NHF) has been introduced for the management of hypoxemic respiratory failure in adults with favorable effects on ventilation and respiratory mechanics. The above mentioned NHF positive effects has been observed also in stable COPD patients with or without chronic hypercapnia. In this study, the investigators hypothesize that NHF is not inferior to NIV for respiratory support in patients with COPD exacerbation and acute or acute on chronic hypercapnic respiratory failure.

Detailed Description
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The use of non-invasive ventilation (NIV) in COPD exacerbation has increased significantly over time since it has been shown to improve acute respiratory acidosis (increases pH and decreases PaCO2), decrease respiratory rate, work of breathing, severity of breathlessness and therefore reduce mortality and intubation rates. Despite all these favorable effect, a great percentage of patients ( 30%) present contraindications to NIV or cannot tolerate it increasing thus the possibility of NIV failure and consequently intubation rates. Over the past decade, nasal high flow (NHF) oxygen therapy has been introduced for the management of hypoxemic respiratory failure in adults. NHF can generate high flow rates up to 60 L·min-1 and through this mechanism exerts its positive effects on respiratory mechanics, carbon dioxide washout, patient's respiratory rate and work of breathing. Although the above mentioned NHF positive effects has been observed also in stable COPD patients with or without chronic hypercapnia, NHF use in COPD exacerbation is questionable and only a few case reports studies have been published showing favorable effects of NHF on COPD exacerbation. In this study, the investigators hypothesize that NHF is not inferior to NIV for respiratory support in patients with COPD exacerbation and acute or acute on chronic hypercapnic respiratory failure.

Official Title
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Nasal High Flow Versus Non-Invasive Ventilation in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease, Respiratory Failure, Acute Exacerbation Copd

Intervention / Treatment
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* Device: Nasal High Flow
* Device: Non-Invasive Ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with mild to moderate COPD exacerbation and the following characteristics persisting after initial medical therapy with bronchodilators and controlled oxygen therapy 7,25<pH<7,35 PaCO2>45mmHg RR>23 Ability to obtain written informed consent by the patient or patient's next of kin Exclusion Criteria: severe facial deformity Facial burns Fixed upper airway obstruction Criteria for imminent intubation and invasive mechanical ventilation (any of the following) respiratory or cardiac arrest gasping respiration pH <7.15 depressed consciousness (Glasgow Coma Score <8) psychomotor agitation inadequately controlled by sedation massive aspiration persistent inability to remove respiratory secretions heart rate < 50 ·min-1 with loss of alertness severe hemodynamic instability without response to fluids and vasoactive drugs severe ventricular arrhythmias

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nasal High Flow<br>Patients randomized to NHF device with initial settings of flow=50-60 L·min-1, temperature=37ο Celsius and FiO2 adjusted to maintain SpO2 between 88%-92%. | Device: Nasal High Flow<br>* Patients admitted to emergency department with COPD exacerbation combined with mild to moderate acute or acute on chronic hypercapnic respiratory failure will be randomized in one of the two study groups. In case of NHF it will be commence immediately with pre-defined settings<br>|
| Active Comparator: Non-Invasive Ventilation<br>Patients randomized to NIV with initial settings EPAP=3cmH2O, IPAP=15cmH2O, I:E=1:2 to 1:3, inspiratory time=0.8-1.2sec and FiO2 adjusted to maintain SpO2 between 88%-92%. | Device: Non-Invasive Ventilation<br>* Patients admitted to emergency department with COPD exacerbation combined with mild to moderate acute or acute on chronic hypercapnic respiratory failure will be randomized in one of the two study groups. In case of NIV it will be commence immediately with pre-defined settings<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of treatment failure | As treatment failure is defined any need to switch to other treatment group because of discomfort, intolerance or failure to improve physiologic parameters (especially respiratory rate and ABG) despite optimum settings | The first assessment will be held at 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on respiratory rate | This secondary outcome includes changes on respiratory rate (breaths per minute) | They will be assessed on baseline, before NIV or NHF initiation, and on 1, 2, 4, 6, 12, 24, 48 hours and once daily after day 3. | 
| Changes on arterial partial pressure of oxygen | This secondary outcome includes changes on arterial partial pressure of oxygen values (unit of measure will be mmHg) | They will be assessed on baseline, before NIV or NHF initiation, and on 1, 2, 4, 6, 12, 24, 48 hours and once daily after day 3. | 
| Changes on arterial partial pressure of carbon dioxide | This secondary outcome includes changes on arterial partial pressure of carbon dioxide (unit of measure will be mmHg) | They will be assessed on baseline, before NIV or NHF initiation, and on 1, 2, 4, 6, 12, 24, 48 hours and once daily after day 3. | 
| Changes on arterial pH | This secondary outcome includes changes on arterial pH values | They will be assessed on baseline, before NIV or NHF initiation, and on 1, 2, 4, 6, 12, 24, 48 hours and once daily after day 3. | 
| Changes on respiratory accessory muscle use | This secondary outcome includes recording of respiratory accessory muscle use (recording will be yes or no) | They will be assessed on baseline, before NIV or NHF initiation, and on 1, 2, 4, 6, 12, 24, 48 hours and once daily after day 3. | 
| Patient's dyspnea | Dyspnea will be assessed with a 10-point visual analog scale and also Borg scale for dyspnea | They will be assessed on baseline, before NIV or NHF initiation, and on 1, 2, 4, 6, 12, 24, 48 hours and once daily after day 3 (in those subjects whose neurological status allowed them to complete the evaluation) | 
| Pulmonary complications | Any pulmonary complication will be assessed and correlated with the allocated treatment | They will be assessed on baseline, before NIV or NHF initiation, and on 1, 2, 4, 6, 12, 24, 48 hours and once daily after day 3. | 
| Extrapulmonary complications | Any extrapulmonary complication will be assessed and correlated with the allocated treatment | They will be assessed on baseline, before NIV or NHF initiation, and on 1, 2, 4, 6, 12, 24, 48 hours and once daily after day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-invasive ventilation, Nasal High Flow