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

Andrea Cortegiani, Federico Longhini, Annalisa Carlucci, Raffaele Scala, Paolo Groff, Andrea Bruni, Eugenio Garofalo, Maria Rita Taliani, Uberto Maccari, Luigi Vetrugno, Enrico Lupia, Giovanni Misseri, Vittoria Comellini, Antonino Giarratano, Stefano Nava, Paolo Navalesi, Cesare Gregoretti, Andrea Cortegiani, Federico Longhini, Annalisa Carlucci, Raffaele Scala, Paolo Groff, Andrea Bruni, Eugenio Garofalo, Maria Rita Taliani, Uberto Maccari, Luigi Vetrugno, Enrico Lupia, Giovanni Misseri, Vittoria Comellini, Antonino Giarratano, Stefano Nava, Paolo Navalesi, Cesare Gregoretti

Abstract

Background: Noninvasive ventilation (NIV) is indicated to treat respiratory acidosis due to exacerbation of chronic obstructive pulmonary disease (COPD). Recent nonrandomized studies also demonstrated some physiological effects of high-flow nasal therapy (HFNT) in COPD patients. We designed a prospective, unblinded, multicenter, randomized controlled trial to assess the noninferiority of HFNT compared to NIV with respect to the reduction of arterial partial pressure of carbon dioxide (PaCO2) in patients with hypercapnic acute respiratory failure with mild-to-moderate respiratory acidosis.

Methods: We will enroll adult patients with acute hypercapnic respiratory failure, as defined by arterial pH between 7.25 and 7.35 and PaCO2 ≥ 55 mmHg. Patients will be randomly assigned 1:1 to receive NIV or HFNT. NIV will be applied through a mask with a dedicated ventilator in pressure support mode. Positive end-expiratory pressure will be set at 3-5 cmH2O with inspiratory support to obtain a tidal volume between 6 and 8 ml/kg of ideal body weight. HFNT will be initially set at a temperature of 37 °C and a flow of 60 L/min. At 2 and 6 h we will assess arterial blood gases, vital parameters, respiratory rate, treatment intolerance and failure, need for endotracheal intubation, time spent under mechanical ventilation (both invasive and NIV), intensive care unit and hospital length of stay, and hospital mortality. Based on an α error of 5% and a β error of 80%, with a standard deviation for PaCO2 equal to 15 mmHg and a noninferiority limit of 10 mmHg, we computed a sample size of 56 patients. Considering potential drop-outs and nonparametric analysis, the final computed sample size was 80 patients (40 per group).

Discussion: HFNT is more comfortable than NIV in COPD patients recovering from an episode of exacerbation. If HFNT would not be inferior to NIV, HFNT could be considered as an alternative to NIV to treat COPD patients with mild-to-moderate respiratory acidosis.

Trial registration: ClinicalTrials.gov, NCT03370666 . Registered on December 12, 2017.

Keywords: Acute respiratory failure; Carbon dioxide; Chronic obstructive pulmonary disease; Emergency department; High-flow oxygen therapy through nasal cannula; Intensive care unit; Noninvasive ventilation.

Conflict of interest statement

Prof. Stefano Nava’s institution received an unrestricted research grant from Fisher and Paykel. Prof. Paolo Navalesi’s institution received funding from Maquet Critical Care, Draeger and Intersurgical S.p.A.; he received honoraria/speaking fees from Maquet Critical Care, Orionpharma, Philips, Resmed, Merck Sharp & Dome and Novartis; and he discloses that he contributed to the development of the helmet Next, whose license for patent belongs to Intersurgical S.P.A., and receives royalties for that invention.

Prof. Federico Longhini and Prof. Paolo Navalesi contributed to the development of a device not discussed in the present study whose patent is in progress (European Patent application number EP20170199831). Dr Paolo Groff received fees for lectures from Aspen Pharmaceuticals and Menarini Pharmaceuticals (not relevant to this protocol). Prof. Cesare Gregoretti received fees for lectures or consultancies from Philips, Resmed, Vivisol, OrionPharma and Origin (not relevant to this protocol). The remaining authors disclose that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
A schedule for enrolment, intervention and assessment according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) indications. HFNT high-flow nasal therapy through nasal cannula, ICU intensive care unit, NIV noninvasive ventilation
Fig. 2
Fig. 2
Study flow chart according to CONsolidated Standards of Reporting Trials. COPD chronic obstructive pulmonary disease, HFNT high-flow nasal therapy through nasal cannula, ICU intensive care unit, NIV noninvasive ventilation, PaCO2 arterial partial pressure of carbon dioxide

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