Clinical trial NCT03370666: High Flow Nasal Therapy Versus Noninvasive Ventilation in COPD Exacerbation
Official title: High Flow Nasal Therapy Versus Noninvasive Ventilation in Mild to Moderate Acute Hypercapnic Respiratory Failure: A Non-inferiority Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COPD Exacerbation
Lead sponsor: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera Universitaria Mater Domini, Catanzaro
First posted: 2017-12-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non-inferiority
Primary purpose: TREATMENT

Brief summary: 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: 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%.

Eligibility criteria: 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.

Primary outcomes:
measure: Arterial partial pressure of carbon dioxide (PaCO2)
timeFrame: 2 hours after randomization
Secondary outcomes:
measure: Dyspnea evaluated with Borg dyspnea scale
timeFrame: 2 and 6 hours after randomization
measure: Arterial partial pressure of carbon dioxide (PaCO2)
timeFrame: 6 hours after randomization
Other outcomes:
measure: Respiratory rate
timeFrame: 2 and 6 hours after randomization
measure: Discontinuation of the interventions
timeFrame: At 6 hours after randomization
measure: Overall discomfort related to the interface
timeFrame: At 6 hours after randomization
measure: Presence of side effects
timeFrame: At 6 hours after randomization
measure: Rate of treatment failure
timeFrame: At 6 hours after randomization
measure: Rate of endotracheal intubation
timeFrame: At 6 hours after randomization
Locations:
city: Arezzo
country: Italy
facility: Ospedale S. Donato
city: Bologna
country: Italy
facility: Ospedale Sant'Orsola Malpighi. Università Alma Mater
city: Catania
country: Italy
facility: A.O.U. Policlinico-Vittorio Emanuele, Università degli Studi di Catania
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Universitaria Mater Domini
city: Modena
country: Italy
facility: University Hospital of Modena, Pneumology Unit and Center for Rare Lung Diseases, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone. Università degli Studi di Palermo
city: Pavia
country: Italy
facility: IRCCS Maugeri
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia
city: Torino
country: Italy
facility: Ospedale Molinette
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine
Study officials:
affiliation: Azienda Ospedaliera Universitaria Mater Domini, Catanzaro
name: Paolo Navalesi, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.