Nasal high flow or noninvasive ventilation? navigating hypercapnic COPD exacerbation treatment: A randomized noninferiority clinical trial.

Noninvasive ventilation (NIV) has been the cornerstone for managing acute exacerbations of COPD (AECOPD) with hypercapnic respiratory failure. Nasal high flow (NHF) oxygen therapy has emerged as a potential alternative, offering a more tolerable modality with promising outcomes. The aim of the present study was to evaluate whether NHF respiratory support is noninferior to NIV with respect to treatment failure, in patients with mild-to-moderate hypercapnic AECOPD. In this multi-center, randomized, noninferiority trial, 105 patients with AECOPD and respiratory failure type II were enrolled. Participants were randomly assigned to receive either NHF therapy or NIV. The primary endpoint was the frequency of treatment failure, defined as the need for intubation and invasive mechanical ventilation or a switch to the alternative treatment group. Secondary endpoints included changes in respiratory parameters, patient comfort indicators, and the occurrence of complications. The findings revealed no significant difference in the primary outcome between the groups, with a treatment failure rate of 19.6 % (10 out of 51) in the NHF group and 14.8 % (8 out of 54) in the NIV group. Interestingly, NHF users reported significantly lower levels of dyspnea and discomfort at multiple follow-up points. Despite the differences in patient comfort, respiratory parameters such as respiratory rate, arterial blood gases, and use of accessory muscles of respiration showed no significant disparities between the groups throughout the study period. NHF therapy was similar to NIV in preventing treatment failure among patients with hypercapnic AECOPD, offering a viable alternative with enhanced comfort. The study was prospectively registered in ClinicalTrials.gov (Identifier: NCT03466385) on March 15, 2018.

Pantazopoulos I ，Boutlas S ，Mavrovounis G ，Papalampidou A ，Papagiannakis N ，Kontou M ，Bibaki E ，Athanasiou N ，Meletis G ，Gourgoulianis K ，Zakynthinos S ，Ischaki E ... -  《-》

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.

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 ... -  《Trials》

High flow nasal cannula oxygen therapy versus non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease with acute-moderate hypercapnic respiratory failure: a randomized controlled non-inferiority trial.

Although cumulative studies have demonstrated a beneficial effect of high-flow nasal cannula oxygen (HFNC) in acute hypercapnic respiratory failure, randomized trials to compare HFNC with non-invasive ventilation (NIV) as initial treatment in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients with acute-moderate hypercapnic respiratory failure are limited. The aim of this randomized, open label, non-inferiority trial was to compare treatment failure rates between HFNC and NIV in such patients. Patients diagnosed with AECOPD with a baseline arterial blood gas pH between 7.25 and 7.35 and PaCO2 ≥ 50 mmHg admitted to two intensive care units (ICUs) at a large tertiary academic teaching hospital between March 2018 and December 2022 were randomly assigned to HFNC or NIV. The primary endpoint was the rate of treatment failure, defined as endotracheal intubation or a switch to the other study treatment modality. Secondary endpoints were rates of intubation or treatment change, blood gas values, vital signs at one, 12, and 48 h, 28-day mortality, as well as ICU and hospital lengths of stay. 225 total patients (113 in the HFNC group and 112 in the NIV group) were included in the intention-to-treat analysis. The failure rate of the HFNC group was 25.7%, while the NIV group was 14.3%. The failure rate risk difference between the two groups was 11.38% (95% CI 0.25-21.20, P = 0.033), which was higher than the non-inferiority cut-off of 9%. In the per-protocol analysis, treatment failure occurred in 28 of 110 patients (25.5%) in the HFNC group and 15 of 109 patients (13.8%) in the NIV group (risk difference, 11.69%; 95% CI 0.48-22.60). The intubation rate in the HFNC group was higher than in the NIV group (14.2% vs 5.4%, P = 0.026). The treatment switch rate, ICU and hospital length of stay or 28-day mortality in the HFNC group were not statistically different from the NIV group (all P > 0.05). HFNC was not shown to be non-inferior to NIV and resulted in a higher incidence of treatment failure than NIV when used as the initial respiratory support for AECOPD patients with acute-moderate hypercapnic respiratory failure. chictr.org (ChiCTR1800014553). Registered 21 January 2018, http://www.chictr.org.cn.

Tan D ，Wang B ，Cao P ，Wang Y ，Sun J ，Geng P ，Walline JH ，Wang Y ，Wang C ... -  《CRITICAL CARE》

Nasal high-flow compared to non-invasive ventilation in treatment of acute acidotic hypercapnic exacerbation of chronic obstructive pulmonary disease-protocol for a randomized controlled noninferiority trial (ELVIS).

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a major negative impact on health status, rates of hospitalization, readmission, disease progression and mortality. Non-invasive ventilation (NIV) is the standard therapy for hypercapnic acidotic respiratory failure in AECOPD. Despite its beneficial effects, NIV is often poorly tolerated (11-34 % failure rate). An increasing number of studies have documented a beneficial effect of nasal high-flow (NHF) in acute hypercapnia. We designed a prospective, randomized, multi-centre, open label, non-inferiority trial to compare treatment failure in nasal NHF vs NIV in patients with acidotic hypercapnic AECOPD. The study will be conducted in about 35 sites in Germany. Patients with hypercapnic AECOPD with respiratory acidosis (pH < 7.35) will be randomized 1:1 to NIV or NHF. The primary outcome is the combined endpoint of intubation, treatment failure or death at 72 h. The switch from one to the other device marks a device failure but acts as a rescue treatment in absence of intubation criteria. A sample size of 720 was calculated to have 80% power for showing that NHF is non-inferior to NIV with a margin of 8 percentage points. Linear regression will be used for the confirmatory analysis. If NHF is shown to be non-inferior to NIV in acidotic hypercapnic AECOPD, it could become an important alternative treatment. ClinicalTrials.gov , NCT04881409 , Registered on May 11, 2021.

Bräunlich J ，Köppe-Bauernfeind N ，Petroff D ，Franke A ，Wirtz H ... -  《-》

Nasal high-flow therapy compared with non-invasive ventilation in COPD patients with chronic respiratory failure: A randomized controlled cross-over trial.

Non-invasive ventilation (NIV) is part of the standard of care for hypercapnic respiratory failure secondary to COPD, but may be poorly tolerated. Preliminary evidence suggests nasal high-flow (NHF) therapy may improve hypercapnia in COPD and be well tolerated. We compared NHF and NIV in people with COPD and chronic hypercapnic respiratory failure. Single-blind randomized controlled two-way cross-over single-centre trial was conducted in New Zealand. Twenty-four participants with stable hypercapnic COPD received: NHF at 45 L/min and NIV at 15/4 cm H2 O, each for 60 min with a 15-min washout in between. The primary outcome was transcutaneous partial pressure of carbon dioxide (PtCO2 ) at 60 min, adjusted for baseline. NIV reduced the PtCO2 more than NHF (mean (SD) at 60 min by -5.3 (5.0) vs -2.5 (3.5) mm Hg; difference: -2.8 (-5.0 to -0.5) P = 0.021). Difference across all time points was -2.5 mm Hg (95% CI -4.5 to -0.5, P = 0.016). There was no significant difference in the proportion of participants with a reduction of PtCO2  ≥ 4 or ≥ 8 mm Hg. Participants rated NHF significantly better for ease of application, comfort and fit. In stable COPD patients with chronic hypercapnia, NIV resulted in a greater reduction in PtCO2 compared with NHF, which was of uncertain clinical significance. NHF was better tolerated than NIV and may be a therapeutic option for some people with hypercapnic respiratory failure. ACTRN12616001701415 at www.anzctr.org.au.

McKinstry S ，Singer J ，Baarsma JP ，Weatherall M ，Beasley R ，Fingleton J ... -  《-》