High Flow Nasal Therapy Versus Noninvasive Ventilation in COPD Exacerbation

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

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.

Study Overview

• Status: Completed
• Conditions: COPD Exacerbation
• Intervention / Treatment: Other: HFNT; Other: NIV

Detailed Description

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%.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Arezzo, Italy
    • Ospedale S. Donato
  • Bologna, Italy
    • Ospedale Sant'Orsola Malpighi. Università Alma Mater
  • Catania, Italy
    • A.O.U. Policlinico-Vittorio Emanuele, Università degli Studi di Catania
  • Catanzaro, Italy
    • Azienda Ospedaliera Universitaria Mater Domini
  • Modena, Italy
    • University Hospital of Modena, Pneumology Unit and Center for Rare Lung Diseases, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia
  • Palermo, Italy
    • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone. Università degli Studi di Palermo
  • Pavia, Italy
    • IRCCS Maugeri
  • Perugia, Italy
    • Azienda Ospedaliera di Perugia
  • Torino, Italy
    • Ospedale Molinette
  • Udine, Italy
    • Azienda Sanitaria Universitaria integrata di Udine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HFNT; 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; High flow nasal therapy
ACTIVE_COMPARATOR: NIV; 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; Noninvasive ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory rate		2 and 6 hours after randomization
Discontinuation of the interventions	The inability of the patient to continue the treatment while there was still an indication for ventilatory support	At 6 hours after randomization
Overall discomfort related to the interface		At 6 hours after randomization
Presence of side effects	I.e., complaining for noise or too high temperature of flow, claustrophobia, gastric distension, vomiting, sweating, tightness	At 6 hours after randomization
Rate of treatment failure	defined as the presence of one or more of the following: arterial partial pressure of carbon dioxide (PaCO2) reduction, no change or reduction < 10 mmHg from baseline, worsening or no improvement in dyspnoea, respiratory rate > 30 breaths per minute, use of accessory respiratory muscles or paradoxical abdominal movement	At 6 hours after randomization
Rate of endotracheal intubation	Number of patients requiring endotracheal intubation	At 6 hours after randomization

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
• Collaborators: Azienda Ospedaliera Universitaria Mater Domini, Catanzaro
• Investigators: Study Director: Paolo Navalesi, MD, Azienda Ospedaliera Universitaria Mater Domini, Catanzaro

Publications and helpful links

General Publications

• Cortegiani A, Longhini F, Madotto F, Groff P, Scala R, Crimi C, Carlucci A, Bruni A, Garofalo E, Raineri SM, Tonelli R, Comellini V, Lupia E, Vetrugno L, Clini E, Giarratano A, Nava S, Navalesi P, Gregoretti C; H. F.-AECOPD study investigators. High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial. Crit Care. 2020 Dec 14;24(1):692. doi: 10.1186/s13054-020-03409-0.
• Cortegiani A, Longhini F, Carlucci A, Scala R, Groff P, Bruni A, Garofalo E, Taliani MR, Maccari U, Vetrugno L, Lupia E, Misseri G, Comellini V, Giarratano A, Nava S, Navalesi P, Gregoretti C. High-flow nasal therapy versus noninvasive ventilation in COPD patients with mild-to-moderate hypercapnic acute respiratory failure: study protocol for a noninferiority randomized clinical trial. Trials. 2019 Jul 22;20(1):450. doi: 10.1186/s13063-019-3514-1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 15, 2018
• Primary Completion (ACTUAL): March 25, 2020
• Study Completion (ACTUAL): April 15, 2020

Study Registration Dates

• First Submitted: November 29, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (ACTUAL): December 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 30, 2020
• Last Update Submitted That Met QC Criteria: April 29, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 07/17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No