Top

Trials

Published in:

Open Access 01-12-2022 | Non-Invasive Ventilation | Study protocol

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)

Authors: Jens Bräunlich, Nicole Köppe-Bauernfeind, David Petroff, Annegret Franke, Hubert Wirtz

Published in: Trials | Issue 1/2022

Abstract

Background

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.

Methods

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.

Discussion

If NHF is shown to be non-inferior to NIV in acidotic hypercapnic AECOPD, it could become an important alternative treatment.

Trial registration

ClinicalTrials.gov, NCT04881409, Registered on May 11, 2021

Available only for authorised users

Decker R. 2020 GOLD REPORT. https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.1wms.pdf. Published online December 12, 2019:1-141.

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. Samet J, ed. PLoS medicine. 2006;3(11):e442. doi:https://doi.org/10.1371/journal.pmed.0030442

Soriano JB, Abajobir AA, Abate KH, Abera SF, Agrawal A, Ahmed MB, et al. Articles Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017;5(9):691–706. https://doi.org/10.1016/s2213-2600(17)30293-x.CrossRef

Hartl S, Lopez-Campos JL, Pozo-Rodriguez F, Castro-Acosta A, Studnicka M, Kaiser B, et al. Risk of death and readmission of hospital-admitted COPD exacerbations: European COPD Audit. Eur Respir J. 2016;47(1):113–21. https://doi.org/10.1183/13993003.01391-2014.CrossRefPubMed

Osadnik CR, Tee VS, Carson-Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017;7(7):CD004104. https://doi.org/10.1002/14651858.cd004104.pub4.CrossRefPubMed

Rochwerg B, Brochard L, Elliott MW, Hess D, Hill NS, Nava S, Navalesi (members o P, Antonelli M, Brozek J, Conti G, Ferrer M, Guntupalli K, Jaber S, Keenan S, Mancebo J, Mehta S, Raoof (members o S Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J 2017;50(2):1602426. doi:https://doi.org/10.1183/13993003.02426-2016

Plant PK, Owen JL, Elliott MW. Non-invasive ventilation in acute exacerbations of chronic obstructive pulmonary disease: long term survival and predictors of in-hospital outcome. Thorax. 2001;56(9):708–12. https://doi.org/10.1136/thorax.56.9.708.CrossRefPubMedPubMedCentral

Carrera M, Marin JM, Antón A, et al. A controlled trial of noninvasive ventilation for chronic obstructive pulmonary disease exacerbations. J Crit Care. 2009;24(3):473.e7–14. https://doi.org/10.1016/j.jcrc.2008.08.007.CrossRef

Confalonieri M, Garuti G, Cattaruzza MS, Osborn JF, Antonelli M, Conti G, et al. Italian noninvasive positive pressure ventilation (NPPV) study group. A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. Eur Respir J. 2005;25(2):348–55. https://doi.org/10.1183/09031936.05.00085304.CrossRefPubMed

10.

Tissot A, Jaffre S, Gagnadoux F, et al. Home non-invasive ventilation fails to improve quality of life in the elderly: results from a multicenter cohort study. Staffieri F, ed. PloS one. 2015;10(10):e0141156. doi:https://doi.org/10.1371/journal.pone.0141156

11.

Bräunlich J, Mauersberger F, Wirtz H. Effectiveness of nasal highflow in hypercapnic COPD patients is flow and leakage dependent. BMC Pulm Med. 2018;18(1):14. https://doi.org/10.1186/s12890-018-0576-x.CrossRefPubMedPubMedCentral

12.

Bräunlich J, Beyer D, Mai D, Hammerschmidt S, Seyfarth HJ, Wirtz H. Effects of nasal high flow on ventilation in volunteers, COPD and idiopathic pulmonary fibrosis patients. Respiration. 2013;85(4):319–25. https://doi.org/10.1159/000342027.CrossRefPubMed

13.

Bräunlich J, Goldner F, Wirtz H. Nasal highflow eliminates CO2 from lower airways. Respir Physiol Neurobiol. 2017;242:86–8. https://doi.org/10.1016/j.resp.2017.03.012.CrossRefPubMed

14.

Bräunlich J, Dellweg D, Bastian A, Budweiser S, Randerath W, Triché D, et al. Nasal high-flow versus noninvasive ventilation in patients with chronic hypercapnic COPD. Int J Chronic Obstruct Pulmonary Dis. 2019;14:1411–21. https://doi.org/10.2147/copd.s206111.CrossRef

15.

Biselli P, Fricke K, Grote L, et al. Reductions in dead space ventilation with nasal high flow depend on physiological dead space volume: metabolic hood measurements during sleep in patients with COPD and controls. Eur Respir J. 2018;51(5). https://doi.org/10.1183/13993003.02251-2017.

16.

Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. New Engl J Medicine. 2015;372(23):2185–96. https://doi.org/10.1056/nejmoa1503326.CrossRef

17.

Maggiore SM, Idone FA, Vaschetto R, Festa R, Cataldo A, Antonicelli F, et al. Nasal high-flow versus venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190(3):282–8. https://doi.org/10.1164/rccm.201402-0364oc.CrossRefPubMed

18.

Hernández G, Vaquero C, Colinas L, Cuena R, González P, Canabal A, et al. Effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: a randomized clinical trial. JAMA. 2016;316(15):1565–74. https://doi.org/10.1001/jama.2016.14194.CrossRefPubMed

19.

Bräunlich J, Wirtz H. Nasal high-flow in acute hypercapnic exacerbation of COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:3895–7. https://doi.org/10.2147/copd.s185001.CrossRefPubMedPubMedCentral

20.

Bräunlich J, Köhler M, Wirtz H. Nasal highflow improves ventilation in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:1077–85. https://doi.org/10.2147/copd.s104616.CrossRefPubMedPubMedCentral

21.

Frizzola M, Miller TL, Rodriguez ME, Zhu Y, Rojas J, Hesek A, et al. High-flow nasal cannula: impact on oxygenation and ventilation in an acute lung injury model. Pediatr Pulmonol. 2011;46(1):67–74. https://doi.org/10.1002/ppul.21326.CrossRefPubMed

22.

Pisani L, Fasano L, Corcione N, Comellini V, Musti MA, Brandao M, et al. Change in pulmonary mechanics and the effect on breathing pattern of high flow oxygen therapy in stable hypercapnic COPD. Thorax. 2017;72(4):373–5. https://doi.org/10.1136/thoraxjnl-2016-209673.CrossRefPubMed

23.

Jeong JH, Kim DH, Kim SC, Kang C, Lee SH, Kang TS, et al. Changes in arterial blood gases after use of high-flow nasal cannula therapy in the ED. Am J Emerg Med. 2015;33(10):1344–9. https://doi.org/10.1016/j.ajem.2015.07.060.CrossRefPubMed

24.

Doshi P, Whittle JS, Bublewicz M, et al. High-velocity nasal insufflation in the treatment of respiratory failure: a randomized clinical trial. Ann Emerg Med. Published online January 5, 2018;72(1):73-83. doi:https://doi.org/10.1016/j.annemergmed.2017.12.006

25.

Lee CC, Mankodi D, Shaharyar S, Ravindranathan S, Danckers M, Herscovici P, et al. High flow nasal cannula versus conventional oxygen therapy and non-invasive ventilation in adults with acute hypoxemic respiratory failure: a systematic review. Respiratory Med. 2016;121:100–8. https://doi.org/10.1016/j.rmed.2016.11.004.CrossRef

26.

Pisani L, Betti S, Biglia C, et al. Effects of high-flow nasal cannula in patients with persistent hypercapnia after an acute COPD exacerbation: a prospective pilot study. BMC Pulm Med. 2020;20(1):12. Published online January 11, 2020:1-9. doi:https://doi.org/10.1186/s12890-020-1048-7

27.

Windisch W, Freidel K, Schucher B, Baumann H, Wiebel M, Matthys H, et al. The Severe Respiratory Insufficiency (SRI) Questionnaire: a specific measure of health-related quality of life in patients receiving home mechanical ventilation. J Clin Epidemiol. 2003;56(8):752–9. https://doi.org/10.1016/S0895-4356(03)00088-X.CrossRefPubMed

28.

Jones PW, Quirk FH, Baveystock CM. The St George’s Respiratory Questionnaire. Respiratory Med. 1991;85 Suppl B:25-31-discussion 33-7.

29.

Jones PW. A self-complete measure of health status for chronic airflow limitation. The St. George’s Respiratory Questionnaire. Am Rev Respir Dis. 1992;145(6):1321–7. https://doi.org/10.1164/ajrccm/145.6.1321.CrossRefPubMed

30.

Committee for Medicinal Products for Human Use (CHMP): Guideline on the choice of the non-inferiority margin. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-choice-non-inferiority-margin_en.pdf) Published online May 30, 2006.

31.

Hintze JPASS. Kaysville. Utah, USA: NCSS; 2011. (Software)

32.

Rochwerg B, Einav S, Chaudhuri D, Mancebo J, Mauri T, Helviz Y, et al. The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline. Intensive Care Med. 2020;46(12):1–12. https://doi.org/10.1007/s00134-020-06312-y.CrossRef

33.

Ferreyro BL, Angriman F, Munshi L, del Sorbo L, Ferguson ND, Rochwerg B, et al. Association of noninvasive oxygenation strategies with all-cause mortality in adults with acute hypoxemic respiratory failure. JAMA. 2020;324(1):57–11. https://doi.org/10.1001/jama.2020.9524.CrossRefPubMed

34.

Bräunlich J, Seyfarth HJ, Wirtz H. Nasal high-flow versus non-invasive ventilation in stable hypercapnic COPD: a preliminary report. Multidiscip Respir Med. 2015;10(1):27. https://doi.org/10.1186/s40248-015-0019-y.CrossRefPubMedPubMedCentral

35.

Cortegiani A, Longhini F, Madotto F, et al. High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial. Crit Care. 2020;24(1):692. https://doi.org/10.1186/s13054-020-03409-0.CrossRefPubMedPubMedCentral

Title: 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)
Authors: Jens Bräunlich
Nicole Köppe-Bauernfeind
David Petroff
Annegret Franke
Hubert Wirtz
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Non-Invasive Ventilation
Chronic Obstructive Lung Disease
Published in: Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-021-05978-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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)

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2022

Exploring the effects of a combined exercise programme on pain and fatigue outcomes in people with systemic sclerosis: study protocol for a large European multi-centre randomised controlled trial

Effectiveness of the Shenzhuo formula in the treatment of patients with macroalbuminuria secondary to diabetic kidney disease: protocol update and statistical analysis plan

PROPENSIX: pressure garment therapy using compressive dynamic Lycra® sleeve to improve bi-manual performance in unilateral cerebral palsy: a multicenter randomized controlled trial protocol

Self-guided digital treatment with virtual reality for panic disorder and agoraphobia: a study protocol for a randomized controlled trial

Cerebral mechanism of Tuina analgesia in management of knee osteoarthritis using multimodal MRI: study protocol for a randomised controlled trial

High-dose Intensity-modulated proton therapy versus Standard-dose Intensity-modulated RadIation therapy for esophageal squamous cell carcinoma (HI-SIRI): study protocol for a randomized controlled clinical trial