Continuous positive airway pressure (CPAP) vs noninvasive positive pressure ventilation (NIPPV) vs noninvasive high frequency oscillation ventilation (NHFOV) as post-extubation support in preterm neonates: protocol for an assessor-blinded, multicenter, randomized controlled trial

Yuan Shi, Daniele De Luca, NASal OscillatioN post-Extubation (NASONE) study group, Shi Yuan, Chen Long, Xingwang Zhu, Huanhuan Li, Xiaoyun Zhong, Sijie Song, Zhang Lan, Li Li, Huiqiang Liu, Xiaomei Tong, Xiaojing Xu, Li Feng Cui, Ming Yi, Zhoujie Peng, Li Jie, Dongmei Chen, Weifeng Zhang, Xinzhu Lin, Wang Bin, Weimin Huang, Guangliang Bi, Shaoru He, Yumei Liu, Yang Jie, Gao Weiwei, Wuhua Liang, Yaoxun Wu, Xinnian Pan, Qiufen Wei, Yujun Chen, Bingmei Wei, Ling Liu, Xinghui Zheng, Ding Xu, Wang Fan, Bin Yi, Jingyun Shi, Yuning Li, Li Jiang, Chunming Jiang, Chenghe Tang, Hong Xiong, Huiqing Sun, Wenqing Kang, Dapeng Liu, Falin Xu, Xing Kaihui, Yang Ning, Fang Liu, Shaoguang Lv, Liu Hanchu, Yuan Wenchao, Rui Cheng, Shen Xian, Hui Wu, Laishuan Wang, Zhenying Yang, Zhang Xiao, Xue Jiang, Zhankui Li, Rong Ju, Wang Jin, Wenbin Dong, Ye Xiaoxiu, Benqing Wu, Zheng Jun, Tian Xiuying, Mingxia Li, Yanping Zhu, Nuerya Rejiafu, Li Long, Yangfang Li, Canlin He, Li Li, Hong Ying Mi, Liang Kun, Hong Cao, Linglin Xia, Chuanfeng Li, Zhaoqing Yin, Su Le, Yanxiang Cheng, Liping Shi, Wang Chenhong, Jiajun Zhu, Zhang Xuefeng, Xi Rong Gao, Bo Lv, Liu Chongde, Wang Xiaorong, Chen Liping, Li Lin, Zhang Chunli, Chen Jia, Qiyu Li, Lv Qin, Yanhong Li, Yong Ji, Yanjiang Chen, Jianhua Sun, Jun Bu, Danni Zhong, Zongyan Gao, Han Shuping, Xiaohui Chen, Caiyun Gao, Hongbin Zhu, Zhenguang Li, Hongwei Wu, Xiuyong Cheng, Yuan Shi, Daniele De Luca, NASal OscillatioN post-Extubation (NASONE) study group, Shi Yuan, Chen Long, Xingwang Zhu, Huanhuan Li, Xiaoyun Zhong, Sijie Song, Zhang Lan, Li Li, Huiqiang Liu, Xiaomei Tong, Xiaojing Xu, Li Feng Cui, Ming Yi, Zhoujie Peng, Li Jie, Dongmei Chen, Weifeng Zhang, Xinzhu Lin, Wang Bin, Weimin Huang, Guangliang Bi, Shaoru He, Yumei Liu, Yang Jie, Gao Weiwei, Wuhua Liang, Yaoxun Wu, Xinnian Pan, Qiufen Wei, Yujun Chen, Bingmei Wei, Ling Liu, Xinghui Zheng, Ding Xu, Wang Fan, Bin Yi, Jingyun Shi, Yuning Li, Li Jiang, Chunming Jiang, Chenghe Tang, Hong Xiong, Huiqing Sun, Wenqing Kang, Dapeng Liu, Falin Xu, Xing Kaihui, Yang Ning, Fang Liu, Shaoguang Lv, Liu Hanchu, Yuan Wenchao, Rui Cheng, Shen Xian, Hui Wu, Laishuan Wang, Zhenying Yang, Zhang Xiao, Xue Jiang, Zhankui Li, Rong Ju, Wang Jin, Wenbin Dong, Ye Xiaoxiu, Benqing Wu, Zheng Jun, Tian Xiuying, Mingxia Li, Yanping Zhu, Nuerya Rejiafu, Li Long, Yangfang Li, Canlin He, Li Li, Hong Ying Mi, Liang Kun, Hong Cao, Linglin Xia, Chuanfeng Li, Zhaoqing Yin, Su Le, Yanxiang Cheng, Liping Shi, Wang Chenhong, Jiajun Zhu, Zhang Xuefeng, Xi Rong Gao, Bo Lv, Liu Chongde, Wang Xiaorong, Chen Liping, Li Lin, Zhang Chunli, Chen Jia, Qiyu Li, Lv Qin, Yanhong Li, Yong Ji, Yanjiang Chen, Jianhua Sun, Jun Bu, Danni Zhong, Zongyan Gao, Han Shuping, Xiaohui Chen, Caiyun Gao, Hongbin Zhu, Zhenguang Li, Hongwei Wu, Xiuyong Cheng

Abstract

Background: Various noninvasive respiratory support modalities are available in neonatal critical care in order to minimize invasive ventilation. Continuous positive airway pressure (CPAP) is the more commonly used but noninvasive positive pressure ventilation (NIPPV) seems more efficacious in the early post-extubation phase, although it is not clear if NIPPV may influence longterm outcomes. A recently introduced alternative is noninvasive high frequency oscillatory ventilation (NHFOV) which might be especially useful in babies needing high constant distending pressure. Preterm neonates may receive these respiratory supports for several weeks. Nonetheless, no data are available for the longterm use of NIPPV and NHFOV; few data exist on NHFOV and clinical outcomes, although its safety and suitability are reported in a number of preliminary short-term studies.

Methods: We designed an assessor-blinded, multicenter, three-arms, parallel, pragmatic, randomized, controlled trial with a superiority design, investigating the use of CPAP vs NIPPV vs NHFOV during the whole stay in neonatal intensive care units in China. Since safety data will also be analyzed it may be considered a phase II/III trial. Moreover, subgroup analyses will be performed on patients according to prespecified criteria based on physiopathology traits: these subgroup analyses should be considered preliminary. At least 1440 neonates are supposed to be enrolled. The trial has been designed with the collaboration of international colleagues expert in NHFOV, who will also perform an interim analysis at the about 50% of the enrolment.

Discussion: The study is applying the best trial methodology to neonatal ventilation, a field where it is often difficult to do so for practical reasons. Nonetheless, ours is also a physiology-driven trial, since interventions are applied based on physiological perspective, in order to use ventilatory techniques at their best. The pragmatic design will increase generalizability of our results but subgroup analyses according to predefined physiopathological criteria are also previewed trying to have some advantages of an explanatory design. Since not all clinicians are well versed in all respiratory techniques, the training is pivotal. We intend to apply particular care to train the participating units: a specific 3-month period and several means have been dedicated to this end.

Trial registration: NCT03181958 (registered on June 9, 2017).

Keywords: Neonate; Non invasive high frequency oscillatory ventilation; Noninvasive respiratory ventilation.

Conflict of interest statement

YS has no interest to declare DDL has received research support, travel grants and/or consultancy fee from Carefusion (now Vyaire), Acutronic and Getinge. Those are industries producing neonatal ventilators. These companies are not involved at all in the study and will not have any role in the conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, approval of the manuscript or decision to submit it for publication. Many different ventilators will be variably used in the trial (see Methods and design).

Figures

Fig. 1
Fig. 1
Neonatal Intensive Care Units participating to the trial. Different colors represent the number of NICU participating in each area
Fig. 2
Fig. 2
Basic study design. Neonates will stay on the assigned intervention until the final weaning. No cross-over allowed. In case of intubation, when the baby will be extubated, he will receive again his original treatment according to randomization
Fig. 3
Fig. 3
Current bronchopulmonary dysplasia definition [24]. The figure represents the algorithms to apply the definition only in babies ≤32 weeks’ gestation, as these are those enrolled in the trial
Fig. 4
Fig. 4
Trial flow-chart according to SPIRIT guidelines [57]. Black squares indicate timepoints when the intervention will surely be provided, while grey squares indicate a time point (36 weeks’ postconceptional age) when the intervention may be provided unless it has been interrupted earlier. All assessments will be performed at the NICU discharge apart from the diagnosis of BPD (that requires evaluation of at 36 weeks’ postconceptional age [24]), safety outcomes and serious adverse events

References

    1. Lemons JA, Bauer CR, Oh W, Korones SB, Papile LA, Stoll BJ, Verter J, Temprosa M, Wright LL, Ehrenkranz RA, Fanaroff AA, Stark A, Carlo W, Tyson JE, Donovan EF, Shankaran S, Stevenson DK. Very low birth weight infant outcomes of the NICHD neonatal research network. Pediatrics. 2001;107:1–8. doi: 10.1542/peds.107.1.e1.
    1. Schmölzer GM, Kumar M, Pichler G, Aziz K, O'Reilly M, Cheung PY. Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis. BMJ. 2013;347:f5980. doi: 10.1136/bmj.f5980.
    1. Subramaniam P, Ho JJ, Davis PG. Prophylactic nasal continuous positive airway pressure for preventing morbidity and mortality in very preterm infants. Cochrane Database Syst Rev. 2016;6:CD001243.
    1. De Paoli AG, Davis PG, Faber B, Morley CJ. Devices and pressure sources for administration of nasal continuous positive airway pressure (NCPAP) in preterm neonates. Cochrane Database Syst Rev. 2008;1:CD002977.
    1. Kieran EA, Twomey AR, Molloy EJ, Murphy JF, O'Donnell CP. Randomized trial of prongs or mask for nasal continuous positive airway pressure in preterm infants. Pediatrics. 2012;130:e1170–e1176. doi: 10.1542/peds.2011-3548.
    1. Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GH, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology. 2017;111:107–125. doi: 10.1159/000448985.
    1. Stefanescu BM, Murphy WP, Hansell BJ, Fuloria M, Morgan TM, Aschner JL. A randomized, controlled trial comparing two different continuous positive airway pressure systems for the successful extubation of extremely low birth weight infants. Pediatrics. 2003;112:1031–1038. doi: 10.1542/peds.112.5.1031.
    1. Barrington KJ, Bull D, Finer NN. Randomized trial of nasal synchronized intermittent mandatory ventilation compared with continuous positive airway pressure after extubation of very low birth weight infants. Pediatrics. 2001;107:638–641. doi: 10.1542/peds.107.4.638.
    1. Davis PG, Henderson-Smart DJ. Nasal continuous positive airways pressure immediately after extubation for preventing morbidity in preterm infants. Cochrane Database Syst Rev. 2003;2:CD000143.
    1. Greenough A. Long-term pulmonary outcome in the preterm infant. Neonatology. 2008;93:324–327. doi: 10.1159/000121459.
    1. Chien YH, Tsao PN, Chou HC, Tang JR, Tsou KI. Rehospitalization of extremely-low-birth-weight infants in first 2 years of life. Early Hum Dev. 2002;66:33–40. doi: 10.1016/S0378-3782(01)00233-X.
    1. Lemyre B, Davis PG, De Paoli AG, Kirpalani H. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev. 2017;2:CD003212.
    1. De Luca Daniele, Dell'Orto Valentina. Non-invasive high-frequency oscillatory ventilation in neonates: review of physiology, biology and clinical data. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2016;101(6):F565–F570. doi: 10.1136/archdischild-2016-310664.
    1. Czernik C, Schmalisch G, Bührer C, Proquitté H. Weaning of neonates from mechanical ventilation by use of nasopharyngeal high frequency oscillatory ventilation: a preliminary study. J Matern Fetal Neonatal Med. 2012;25:374–378. doi: 10.3109/14767058.2011.580401.
    1. Mukerji A, Sarmiento K, Lee B, Hassall K, Shah V. Non-invasive high-frequency ventilation versus bi-phasic continuous positive airway pressure (BP-CPAP) following CPAP failure in infants <1250 g: a pilot randomized controlled trial. J Perinatol. 2017;37:49–53. doi: 10.1038/jp.2016.172.
    1. De Luca D. Noninvasive high-frequency ventilation and the errors from the past: designing simple trials neglecting complex respiratory physiology. J Perinatol. 2017;37:1065–1066. doi: 10.1038/jp.2017.84.
    1. Fisher HS, Bohlin K, Bührer C, Schmalisch G, Cremer M, Reiss I, Czernik C. Nasal high-frequency oscillation ventilation in neonates: a survey in five European countries. Eur J Pediatr. 2015;174:465–471. doi: 10.1007/s00431-014-2419-y.
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Evereaux PJ, Elbourne D, Egger M, Altman DG. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c869. doi: 10.1136/bmj.c869.
    1. Restrepo RD, Hirst KR, Wittnebel L, Wettstein R. AARC clinical practice guideline: transcutaneous monitoring of carbon dioxide and oxygen: 2012. Respir Care. 2012;57:1955–1962. doi: 10.4187/respcare.02011.
    1. Silverman WC, Anderson DH. Controlled clinical trial on effects of water mist on obstructive respiratory signs, death rate and necropsy findings among premature infants. Pediatrics. 1956;17:1–4.
    1. Papile LA, Munsick-Bruno G, Schaefer A. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J Pediatr. 1983;103:273–277. doi: 10.1016/S0022-3476(83)80366-7.
    1. Watkins AM, West CR, Cooke RW. Blood pressure and cerebral hemorrhage and ischaemia in very low birth weight infants. Early Hum Dev. 1989;19:103–110. doi: 10.1016/0378-3782(89)90120-5.
    1. De Luca D, Romain O, Yousef N, Andriamanamirijaa D, Shankar-Aguilera S, Walls E, Sgaggero B, Aube N, Tissières P. Monitorages physiopathologiques en reanimation néonatale. J Ped Puericul. 2015;28:276–300.
    1. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723–1729. doi: 10.1164/ajrccm.163.7.2011060.
    1. International Committee for the Classification of Retinopathy of Prematurity The international classification of retinopathy of prematurity revisited. Arch Ophthalmol. 2005;123:991–999. doi: 10.1001/archopht.123.7.991.
    1. Stoll BJ. Epidemiology of necrotizing enterocolitis. Clin Perinatol. 1994;21:205–218. doi: 10.1016/S0095-5108(18)30341-5.
    1. Fischer C, Bertelle V, Hohlfeld J, Forcada-Guex M, Stadelmann-Diaw C, Tolsa JF. Nasal trauma due to continuous positive airway pressure in neonates. Arch Dis Child Fetal Neonatal Ed. 2010;95:F447–F451. doi: 10.1136/adc.2009.179416.
    1. Stevens B, Johnston C, Petryshen P, Taddio A. Premature infant pain profile :developmend and initial validation. Clin J Pain. 1996;12:13–12. doi: 10.1097/00002508-199603000-00004.
    1. De Paoli AG, Davis PG, Faber B, Morley CJ. Devices and pressure sources for administration of nasal continuous positive airway pressure (NCPAP) in preterm neonates. Cochrane Database Syst Rev. 2002;3:CD002977.
    1. Roberts CT, Davis PG, Owen LS. Neonatal non-invasive respiratory support: synchronised NIPPV, non-synchronised NIPPV or bi-level CPAP: what is the evidence in 2013? Neonatology. 2013;104:203–209. doi: 10.1159/000353448.
    1. Mukerji A, Belik J. Neonatal nasal intermittent positive pressure ventilation efficacy and lung pressure transmission. J Perinatol. 2015;35:716–719. doi: 10.1038/jp.2015.61.
    1. Gerdes JS, Sivieri EM, Abbasi S. Factors influencing delivered mean airway pressure during nasal CPAP with the RAM cannula. Pediatr Pulmonol. 2016;51:60–69. doi: 10.1002/ppul.23197.
    1. De Jaegere A, van Veenendaal MB, Michiels A, van Kaam AH. Lung recruitment using oxygenation during openlunghigh-frequency ventilation in preterm infants. Am J Respir Crit Care Med. 2006;174:639–645. doi: 10.1164/rccm.200603-351OC.
    1. De Luca D, Piastra M, Pietrini D, Conti G. Effect of amplitude and inspiratory time in a bench model of non-invasive HFOV through nasal prongs. Pediatr Pulmonol. 2012;47:1012–1018. doi: 10.1002/ppul.22511.
    1. De Luca D, Carnielli VP, Conti G, Piastra M. Noninvasive high frequency oscillatory ventilation through nasal prongs: bench evaluation of efficacy and mechanics. Intensive Care Med. 2010;36:2094–2100. doi: 10.1007/s00134-010-2054-7.
    1. Mukerji A, Finelli M, Belik J. Nasal high-frequency oscillation for lung carbon dioxide clearance in the newborn. Neonatology. 2013;103:161–165. doi: 10.1159/000345613.
    1. De Luca D, Costa R, Visconti F, Piastra M, Conti G. Oscillation transmission and volume delivery during face mask-delivered HFOV in infants: Bench and in vivo study. Pediatr Pulmonol. 2016;51:705–712. doi: 10.1002/ppul.23403.
    1. Centorrino R, Dell’Orto V, Gitto E, Conti G, De Luca D. Mechanics of nasal mask-delivered HFOV in neonates: a physiologic study. Pediatr Pulmonol. 2019; accepted – in press.
    1. Dell’Orto V, Centorrino R, Shankar-Aguilera S, Ben-Ammar R, Yousef N, De Luca D. Noninvasive high frequency oscillatory ventilation versus noninvasive intermittent positive pressure ventilation for preterm babies developing BPD: a pilot study. E-PAS 2018 in press (Abstract to the Pediatric Academic Societies meeting 2018).
    1. Ramanathan R, Sekar KC, Rasmussen M, Bhatia J, Soll RF. Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <=30 weeks’ gestation: a randomized, controlled trial. J Perinatol. 2012;32:336–343. doi: 10.1038/jp.2012.1.
    1. Faul F, Erdfelder E, Lang AG, Buchner A. G*power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2003;39:175–191. doi: 10.3758/BF03193146.
    1. Parry G, Tucker J, Tarnow-Mordi W. UK neonatal staffing study collaborative group. CRIB II: an update of the clinical risk index for babies score. Lancet. 2003;24(361):1789–1791. doi: 10.1016/S0140-6736(03)13397-1.
    1. Allison PD. Logistic regression using the SAS system. Cary: SAS Institute Ed; 1999.
    1. De Luca Daniele, Harrison David A., Peters Mark J. ‘Lumping or splitting’ in paediatric acute respiratory distress syndrome (PARDS) Intensive Care Medicine. 2018;44(9):1548–1550. doi: 10.1007/s00134-018-5323-5.
    1. Thorpe KE, Zwarenstein M, Oxman AD, Treweek S, Furberg CD, Altman DG, Tunis S, Bergel E, Harvey I, Magid DJ, Chalkidou K. A pragmatic explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 2009;62:464–475. doi: 10.1016/j.jclinepi.2008.12.011.
    1. Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Te Pas A, Plavka R, Roehr CC, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA, Halliday HL. European consensus guidelines on the Management of Respiratory Distress Syndrome - 2019 update. Neonatology. 2019;115:432–451. doi: 10.1159/000499361.
    1. Frerichs I, Amato MB, van Kaam AH, Tingay DG, Zhao Z, Grychtol B, Bodenstein M, Gagnon H, Böhm SH, Teschner E, Stenqvist O, Mauri T, Torsani V, Camporota L, Schibler A, Wolf GK, Gommers D, Leonhardt S. Adler a; TREND study group. Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group. Thorax. 2017;72:83–93. doi: 10.1136/thoraxjnl-2016-208357.
    1. Wolf GK, Arnold JH. Noninvasive assessment of lung volume: respiratory inductance plethysmography and electrical impedance tomography. Crit Care Med. 2005;33(3 Suppl):S163–S169. doi: 10.1097/01.CCM.0000155917.39056.97.
    1. Raimondi F, Yousef N, Migliaro F, Capasso L, De Luca D. Point-of-care lung ultrasound in neonatology: classification into descriptive and functional applications. Pediatr Res. 2018 Jul 20. 10.1038/s41390-018-0114-9 [Epub ahead of print].
    1. Li J, Li X, Huang X, Zhang Z. Noninvasive high-frequency oscillatory ventilation as respiratory support in preterm infants: a meta-analysis of randomized controlled trials. Respir Res. 2019;20(1):58. doi: 10.1186/s12931-019-1023-0.
    1. Shankar-Aguilera S, Taveira M, De Luca D. Neonatal ventilation trials need specific funding. Lancet Respir Med. 2014;2:867–869. doi: 10.1016/S2213-2600(14)70194-8.
    1. De Luca D, van Kaam AH, Tingay DG, Courtney SE, Danhaive O, Carnielli VP, Zimmermann LJ, Kneyber MCJ, Tissieres P, Brierley J, Conti G, Pillow JJ, Rimensberger PC. The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity. Lancet Respir Med. 2017;5:657–666. doi: 10.1016/S2213-2600(17)30214-X.
    1. De Luca D, Baroni S, Vento G, Piastra M, Pietrini D, Romitelli F, Capoluongo E, Romagnoli C, Conti G, Zecca E. Secretory phospholipase A2 and neonatal respiratory distress: pilot study on broncho-alveolar lavage. Intensive Care Med. 2008;34:1858–1864. doi: 10.1007/s00134-008-1224-3.
    1. Goldstein B, Giroir B, Randolph A. International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2–8. doi: 10.1097/01.PCC.0000149131.72248.E6.
    1. Piastra M, Yousef N, Brat R, Manzoni P, Mokhtari M, De Luca D. Lung ultrasound findings in meconium aspiration syndrome. Early Hum Dev. 2014;90(Suppl2):S41–S43. doi: 10.1016/S0378-3782(14)50011-4.
    1. Contentin L, Ehrmann S, Giraudeau B. Heterogeneity in the definition of mechanical ventilation duration and ventilator-free days. Am J Respir Crit Care Med. 2014;15(189):998–1002. doi: 10.1164/rccm.201308-1499LE.
    1. Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, Hróbjartsson A, Mann H, Dickersin K, Berlin J, Doré C, Parulekar W, Summerskill W, Groves T, Schulz K, Sox H, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158:200–207. doi: 10.7326/0003-4819-158-3-201302050-00583.

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