High-intensity versus low-intensity noninvasive positive pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (HAPPEN): study protocol for a multicenter randomized controlled trial

Zujin Luo, Chao Wu, Qi Li, Jian Zhu, Baosen Pang, Yan Shi, Yingmin Ma, Zhixin Cao, HAPPEN collaboration group, Baosen Pang, Bing Dai, Bing Sun, Chao Wu, Chao Zhang, Chen Liu, Dan Wang, Dawei Zheng, Dongmei Li, Fucheng An, Hangyong He, Heli Wang, Hongmei Wu, Hongru Liu, Huiqing Ge, Jian Zhu, Jing Zhou, Juan Wang, Kailiang Duan, Kailv Wang, Lianxiang Guo, Lin Chen, Ling Yu, Lirong Liang, Lixin Xie, Longguang Wu, Lujiang Li, Manyan Zhang, Mingdong Hu, Mingwei Chen, Panpan Zhang, Pengfei Li, Qi Li, Qian Li, Qiang Dang, Qingyuan Zhan, Rongbo Wang, Rui Sun, Runxia Shao, Sanhong Zhang, Shengyu Wang, Sijie Liu, Tianjun Chen, Wenshuai Feng, Wujie Lu, Xiaohong Yang, Xiaohua Hou, Xiaoping Zhang, Xiaowu Tan, Xinghui Wu, Xiuhong Jing, Xiuhong Ma, Xiuzhi Yang, Yaoming Hu, Yichong Li, Yingmin Ma, Yonghong Xiang, Yongpeng An, Yongxiang Zhang, Yunhui Lv, Yurong Zhang, Zhaohui Tong, Zhifang Liu, Zhijun Feng, Zhixin Cao, Zhiyang Yin, Zujin Luo, Zujin Luo, Chao Wu, Qi Li, Jian Zhu, Baosen Pang, Yan Shi, Yingmin Ma, Zhixin Cao, HAPPEN collaboration group, Baosen Pang, Bing Dai, Bing Sun, Chao Wu, Chao Zhang, Chen Liu, Dan Wang, Dawei Zheng, Dongmei Li, Fucheng An, Hangyong He, Heli Wang, Hongmei Wu, Hongru Liu, Huiqing Ge, Jian Zhu, Jing Zhou, Juan Wang, Kailiang Duan, Kailv Wang, Lianxiang Guo, Lin Chen, Ling Yu, Lirong Liang, Lixin Xie, Longguang Wu, Lujiang Li, Manyan Zhang, Mingdong Hu, Mingwei Chen, Panpan Zhang, Pengfei Li, Qi Li, Qian Li, Qiang Dang, Qingyuan Zhan, Rongbo Wang, Rui Sun, Runxia Shao, Sanhong Zhang, Shengyu Wang, Sijie Liu, Tianjun Chen, Wenshuai Feng, Wujie Lu, Xiaohong Yang, Xiaohua Hou, Xiaoping Zhang, Xiaowu Tan, Xinghui Wu, Xiuhong Jing, Xiuhong Ma, Xiuzhi Yang, Yaoming Hu, Yichong Li, Yingmin Ma, Yonghong Xiang, Yongpeng An, Yongxiang Zhang, Yunhui Lv, Yurong Zhang, Zhaohui Tong, Zhifang Liu, Zhijun Feng, Zhixin Cao, Zhiyang Yin, Zujin Luo

Abstract

Background: Despite the positive outcomes of the use of noninvasive positive pressure ventilation (NPPV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), NPPV fails in approximately 15% of patients with AECOPD, possibly because the inspiratory pressure delivered by conventional low-intensity NPPV is insufficient to improve ventilatory status for these patients. High-intensity NPPV, a novel form that delivers high inspiratory pressure, is believed to more efficiently augment alveolar ventilation than low-intensity NPPV, and it has been shown to improve ventilatory status more than low-intensity NPPV in stable AECOPD patients. Whether the application of high-intensity NPPV has therapeutic advantages over low-intensity NPPV in patients with AECOPD remains to be determined. The high-intensity versus low-intensity NPPV in patients with AECOPD (HAPPEN) study will examine whether high-intensity NPPV is more effective for correcting hypercapnia than low-intensity NPPV, hence reducing the need for intubation and improving survival.

Methods/design: The HAPPEN study is a multicenter, two-arm, single-blind, prospective, randomized controlled trial. In total, 600 AECOPD patients with low to moderate hypercapnic respiratory failure will be included and randomized to receive high-intensity or low-intensity NPPV, with randomization stratified by study center. The primary endpoint is NPPV failure rate, defined as the need for endotracheal intubation and invasive ventilation. Secondary endpoints include the decrement of arterial carbon dioxide tension from baseline to 2 h after randomization, in-hospital and 28-day mortality, and 90-day survival. Patients will be followed up for 90 days after randomization.

Discussion: The HAPPEN study will be the first randomized controlled study to investigate whether high-intensity NPPV better corrects hypercapnia and reduces the need for intubation and mortality in AECOPD patients than low-intensity NPPV. The results will help critical care physicians decide the intensity of NPPV delivery to patients with AECOPD.

Trial registration: ClinicalTrials.gov, NCT02985918 . Registered on 7 December 2016.

Keywords: Chronic obstructive pulmonary disease; Endotracheal intubation; Exacerbation; High-intensity; Hypercapnia; Low-intensity; Mortality; Noninvasive positive pressure ventilation.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the ethics committee at each participating center. The protocol has reached version 6, in which there were no changes. Relevant amendments to the protocol will be submitted to the ethics committee for further approval, as warranted. Written informed consent to the study will be obtained from the patients, patients’ next of kin, or other surrogate decision makers where appropriate. A trained investigator is collecting the informed consent documents at each site.

Consent for publication

The written informed consent for the analysis and publication of anonymized data will be obtained from the patients, patients’ next of kin, or other surrogate decision makers, where appropriate.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CONSORT diagram. AECOPD acute exacerbation of chronic obstructive pulmonary disease, NPPV noninvasive positive pressure ventilation, VT tidal volume, IPAP inspiratory positive airway pressure
Fig. 2
Fig. 2
SPIRIT schedule of enrollment, intervention, and assessments. APACHE Acute Physiology And Chronic Health Evaluation, NPPV noninvasive positive pressure ventilation, GCS Glasgow coma scale ICU intensive care unit

References

    1. Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med. 2017;195(5):557–582. doi: 10.1164/rccm.201701-0218PP.
    1. Adeloye D, Chua S, Lee C, Basquill C, Papana A, Theodoratou E, et al. Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J Glob Health. 2015;5(2):020415. doi: 10.7189/jogh.05.020415.
    1. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–2128. doi: 10.1016/S0140-6736(12)61728-0.
    1. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–2196. doi: 10.1016/S0140-6736(12)61729-2.
    1. Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4):347–365. doi: 10.1164/rccm.201204-0596PP.
    1. Song Y, Chen R, Zhan Q, Chen S, Luo Z, Ou J, Wang C. The optimum timing to wean invasive ventilation for patients with AECOPD or COPD with pulmonary infection. Int J Chron Obstruct Pulmon Dis. 2016;11:535–542. doi: 10.2147/COPD.S96541.
    1. Chandra D, Stamm JA, Taylor B, Ramos RM, Satterwhite L, Krishnan JA, et al. Outcomes of noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease in the United States, 1998-2008. Am J Respir Crit Care Med. 2012;185(2):152–159. doi: 10.1164/rccm.201106-1094OC.
    1. Cabrini L, Esquinas A, Pasin L, Nardelli P, Frati E, Pintaudi M, et al. An international survey on noninvasive ventilation use for acute respiratory failure in general non-monitored wards. Respir Care. 2015;60(4):586–592. doi: 10.4187/respcare.03593.
    1. Stefan MS, Shieh MS, Pekow PS, Rothberg MB, Steingrub JS, Lagu T, et al. Epidemiology and outcomes of acute respiratory failure in the United States, 2001 to 2009: a national survey. J Hosp Med. 2013;8(2):76–82. doi: 10.1002/jhm.2004.
    1. Walkey AJ, Wiener RS. Use of noninvasive ventilation in patients with acute respiratory failure, 2000-2009: a population-based study. Ann Am Thorac Soc. 2013;10(1):10–17. doi: 10.1513/AnnalsATS.201206-034OC.
    1. Esteban A, Frutos-Vivar F, Muriel A, Ferguson ND, Penuelas O, Abraira V, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013;188(2):220–230. doi: 10.1164/rccm.201212-2169OC.
    1. Hill NS. Noninvasive ventilation for chronic obstructive pulmonary disease. Respir Care. 2004;49(1):72–87.
    1. Brochard L, Mancebo J, Wysocki M, Lofaso F, Conti G, Rauss A, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995;333(13):817–822. doi: 10.1056/NEJM199509283331301.
    1. Kramer N, Meyer TJ, Meharg J, Cece RD, Hill NS. Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med. 1995;151(6):1799–1806. doi: 10.1164/ajrccm.151.6.7767523.
    1. Celikel T, Sungur M, Ceyhan B, Karakurt S. Comparison of noninvasive positive pressure ventilation with standard medical therapy in hypercapnic acute respiratory failure. Chest. 1998;114(6):1636–1642. doi: 10.1378/chest.114.6.1636.
    1. Collaborative Research Group of Noninvasive Mechanical Ventilation for Chronic Obstructive Pulmonary Disease Early use of non-invasive positive pressure ventilation for acute exacerbations of chronic obstructive pulmonary disease: a multicentre randomized controlled trial. Chin Med J. 2005;118(24):2034–2040.
    1. Lightowler JV, Wedzicha JA, Elliott MW, Ram FS. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ. 2003;326(7382):185. doi: 10.1136/bmj.326.7382.185.
    1. Ram FS, Picot J, Lightowler J, Wedzicha JA. Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2004;3:CD004104.
    1. Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet. 2000;355(9219):1931–1935. doi: 10.1016/S0140-6736(00)02323-0.
    1. Contou D, Fragnoli C, Cordoba-Izquierdo A, Boissier F, Brun-Buisson C, Thille AW. Noninvasive ventilation for acute hypercapnic respiratory failure: intubation rate in an experienced unit. Respir Care. 2013;58(12):2045–2052. doi: 10.4187/respcare.02456.
    1. Anton A, Guell R, Gomez J, Serrano J, Castellano A, Carrasco JL, et al. Predicting the result of noninvasive ventilation in severe acute exacerbations of patients with chronic airflow limitation. Chest. 2000;117(3):828–833. doi: 10.1378/chest.117.3.828.
    1. 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):708–712. doi: 10.1136/thorax.56.9.708.
    1. Ambrosino N, Foglio K, Rubini F, Clini E, Nava S, Vitacca M. Non-invasive mechanical ventilation in acute respiratory failure due to chronic obstructive pulmonary disease: correlates for success. Thorax. 1995;50(7):755–757. doi: 10.1136/thx.50.7.755.
    1. Carlucci A, Richard JC, Wysocki M, Lepage E, Brochard L. Noninvasive versus conventional mechanical ventilation. An epidemiologic survey. Am J Respir Crit Care Med. 2001;163(4):874–880. doi: 10.1164/ajrccm.163.4.2006027.
    1. Windisch W, Haenel M, Storre JH, Dreher M. High-intensity non-invasive positive pressure ventilation for stable hypercapnic COPD. Int J Med Sci. 2009;6(2):72–76. doi: 10.7150/ijms.6.72.
    1. Vrijsen B, Chatwin M, Contal O, Derom E, Janssens JP, Kampelmacher MJ, et al. Hot topics in noninvasive ventilation: report of a working group at the International Symposium on Sleep-Disordered Breathing in Leuven, Belgium. Respir Care. 2015;60(9):1337–1362. doi: 10.4187/respcare.03796.
    1. Windisch W, Kostic S, Dreher M, Virchow JC, Jr, Sorichter S. Outcome of patients with stable COPD receiving controlled noninvasive positive pressure ventilation aimed at a maximal reduction of Pa(CO2) Chest. 2005;128(2):657–662. doi: 10.1378/chest.128.2.657.
    1. Dreher M, Storre JH, Schmoor C, Windisch W. High-intensity versus low-intensity non-invasive ventilation in patients with stable hypercapnic COPD: a randomised crossover trial. Thorax. 2010;65(4):303–308. doi: 10.1136/thx.2009.124263.
    1. Cao Z, Luo Z, Hou A, Nie Q, Xie B, An X, et al. Volume-targeted versus pressure-limited noninvasive ventilation in subjects with acute hypercapnic respiratory failure: a multicenter randomized controlled trial. Respir Care. 2016;61(11):1440–1450. doi: 10.4187/respcare.04619.
    1. Ferrer M, Valencia M, Nicolas JM, Bernadich O, Badia JR, Torres A. Early noninvasive ventilation averts extubation failure in patients at risk: a randomized trial. Am J Respir Crit Care Med. 2006;173(2):164–170. doi: 10.1164/rccm.200505-718OC.
    1. Thille AW, Contou D, Fragnoli C, Cordoba-Izquierdo A, Boissier F, Brun-Buisson C. Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors. Crit Care. 2013;17(6):R269. doi: 10.1186/cc13103.
    1. Patrick W, Webster K, Ludwig L, Roberts D, Wiebe P, Younes M. Noninvasive positive-pressure ventilation in acute respiratory distress without prior chronic respiratory failure. Am J Respir Crit Care Med. 1996;153(3):1005–1011. doi: 10.1164/ajrccm.153.3.8630538.
    1. Mehta S, Jay GD, Woolard RH, Hipona RA, Connolly EM, Cimini DM. Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Crit Care Med. 1997;25(4):620–628. doi: 10.1097/00003246-199704000-00011.
    1. O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979;35(3):549–556. doi: 10.2307/2530245.
    1. Cuvelier A, Pujol W, Pramil S, Molano LC, Viacroze C, Muir JF. Cephalic versus oronasal mask for noninvasive ventilation in acute hypercapnic respiratory failure. Intensive Care Med. 2009;35(3):519–526. doi: 10.1007/s00134-008-1327-x.
    1. Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, et al. An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;195(9):1253–1263. doi: 10.1164/rccm.201703-0548ST.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera