High Flow Nasal Therapy Versus Noninvasive Ventilation in COPD Exacerbation

Study Overview
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Brief Summary
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Randomized multicenter non-inferiority trial comparing High flow nasal therapy (HFNT) versus Noninvasive ventilation (NIV) in patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure.

Detailed Description
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The interventions will be delivered in Emergency Departments or Intensive Care Units. The intervention under investigation will be High flow nasal therapy. Investigators will deliver HFNT to enrolled patients using any available device able to produce it. The flow will be initially set at 60 liters per minute and temperature at 37° C. The target will be an oxygen saturation (SpO2) of 88-92%. In case of patient not tolerating these settings, flow and temperature will be titrated to the maximum tolerated level. The intervention will last until one of the following conditions: 1) physician in charge decide to interrupt HFNT and start NIV because the patient shows signs of persisting worsening respiratory failure; 2) physician in charge decide to interrupt HFNT and perform endotracheal intubation and invasive mechanical ventilation because patient shows one or more of these conditions: respiratory arrest, respiratory pauses with loss of consciousness, psychomotor agitation making nursing care impossible, heart rate < 50 with loss of alertness, hemodynamic instability with systolic arterial blood pressure <70 mmHg, development of conditions requiring intubation either to protect the airway or to manage copious tracheal secretions, inability to tolerate the devices; 3) clinical improvement defined as all these conditions: normal mental status, hemodynamic stability, respiratory rate below 25 per minute, absence of activation of accessory respiratory muscles and paradoxical abdominal motion, no dyspnea arterial pH > 7.35, Arterial partial pressure of carbon dioxide (PaCO2) < 70 mmHg and Arterial partial pressure of oxygen (PaO2) > 55 mmHg with an inspired oxygen fraction (FiO2) < 0.35. In case of temporary interruption of the intervention for any cause, patients should receive oxygen supplementation with Venturi mask with a target of SpO2 88-92%.The comparator will be non invasive ventilation (NIV). NIV must be delivered by full or oronasal mask. The ventilator settings will be decided according to the usual practice: maximal tolerated inspiratory pressure to obtain a measured or estimated expired tidal volume of 6-8 mL·kg-1 of body weight and a positive end expiratory pressure (PEEP) between 3 and 5 cmH2O. An interface rotational strategy will be allowed among only different types of masks. The intervention will last until one of the following conditions: 1) physician in charge decide to interrupt NIV and perform endotracheal intubation and invasive mechanical ventilation because patient shows one or more of these conditions: respiratory arrest, respiratory pauses with loss of consciousness, psychomotor agitation making nursing care impossible, heart rate < 50 with loss of alertness, hemodynamic instability with systolic arterial blood pressure <70 mmHg, development of conditions requiring intubation either to protect the airway or to manage copious tracheal secretions, inability to tolerate the devices; 2) clinical improvement defined as all these conditions: normal mental status, hemodynamic stability, respiratory rate below 25 per minute, absence of activation of accessory respiratory muscles and paradoxical abdominal motion, no dyspnoea arterial pH > 7.35, Arterial partial pressure of carbon dioxide (PaCO2) < 70 mmHg and Arterial partial pressure of oxygen (PaO2) > 55 mmHg with an inspired oxygen fraction (FiO2) < 0.35. In case of temporary interruption of NIV for any cause, patients should receive oxygen supplementation with Venturi mask with a target of SpO2 88-92%.

Official Title
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High Flow Nasal Therapy Versus Noninvasive Ventilation in Mild to Moderate Acute Hypercapnic Respiratory Failure: A Non-inferiority Randomized Trial

Conditions
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COPD Exacerbation

Intervention / Treatment
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* Other: HFNT
* Other: NIV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure; 7.25 < pH < 7.35; Arterial Partial pressure of carbon dioxide (PaCO2) equal or greater than 55 mmHg; Age > 18 years/old Exclusion Criteria: Invasive mechanical ventilation in the last 60 days Use of any form of noninvasive ventilation or high flow oxygen through nasal cannula (HFNT) prior to study enrollment after the onset of acute hypercapnic respiratory failure (AHRF); Noninvasive home care ventilation; Unstable clinical condition (need for vasopressors for >24 h, acute coronary syndrome or life-threatening arrhythmias); Refusal of treatment; Agitation (RASS >= +2) or non-cooperation (Kelly Matthay >=5); Failure of more than two organs; Cardiac arrest; Respiratory arrest requiring tracheal intubation; Recent trauma or burns of the neck and face; Pregnancy; Refusal of consent; Inclusion in other research protocols.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Non-inferiority
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HFNT<br>HFNT performed with any available device. The flow will be initially set at 60 liters per minute and temperature at 37° C. The target will be an oxygen saturation (SpO2) of 88-92%. In case of patient not tolerating these settings, flow and temperature will be titrated to the maximum tolerated level. | Other: HFNT<br>* High flow nasal therapy<br>|
| Active Comparator: NIV<br>NIV must be delivered by full or oronasal mask with any available ventilator. The ventilator settings will be decided according to the usual practice: maximal tolerated inspiratory pressure to obtain a measured or estimated expired tidal volume of 6-8 mL·kg-1 of body weight and a positive end expiratory pressure (PEEP) between 3 and 5 cmH2O. An interface rotational strategy will be allowed among only different types of masks. | Other: NIV<br>* Noninvasive ventilation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial partial pressure of carbon dioxide (PaCO2) |  | 2 hours after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dyspnea evaluated with Borg dyspnea scale | Borg dyspnea scale: this is a 12-point validated scale that rates patient's difficulty in breathing. It starts at number 0 where breathing causes no difficulty at all and progresses through number 10 where breathing difficulty is maximal | 2 and 6 hours after randomization | 
| Arterial partial pressure of carbon dioxide (PaCO2) |  | 6 hours after randomization |