nHFOV Versus Invasive Conventional Ventilation for Preterm Neonates With Respiratory Distress Syndrome (nHFOV)

Effectiveness of Non-invasive High Frequency Oscillatory Ventilation (nHFOV) Versus Invasive Conventional Ventilation for Preterm Neonates With Respiratory Distress Syndrome

Preterm neonates usually develop respiratory distress syndrome (RDS) for which they need respiratory support, which may be invasive and non-invasive depend on the availability and individual need. Non-invasive is relatively safe but non-invasive high frequency oscillatory ventilation (nHFOV) is not appropriately evaluated in neonates as primary support. So the investigators hypothesized that nHFOV is relatively safe and effective in comparison with invasive ventilation for preterm neonates with RDS.

Study Overview

• Status: Withdrawn
• Conditions: Respiratory Distress Syndrome in Premature Infant
• Intervention / Treatment: Device: Non-invasive High Frequency Oscillatory Ventilation; Device: Conventional Invasive Ventilation

Detailed Description

Respiratory distress is a common morbidity in preterm neonates that requires respiratory support and surfactant replacement, if not adequately and timely managed may cause multi-organ dysfunction. Respiratory support can be delivered via both non-invasive (NIV) and invasive mode depending upon the availability of ventilators ,experience and comfort level of physician, and availability of department protocol.

Non-invasive ventilation include CPAP (Continuous Positive Airway Pressure), NIPPV (Non-invasive Positive Pressure Ventilation) and nHFOV (Non-invasive High Frequency Oscillatory Ventilation). Non-invasive ventilation is currently the preferred mode of ventilation globally due to its safety profile, early weaning, less barotrauma, volume trauma and other complications.

Literature review reveals reported comparison for some non-invasive modes of ventilation like CPAP and NIPPV versus conventional ventilation however other non-invasive modes such as nHFOV have still not been appropriately evaluated. nHFOV provides 60-1200 breath/minute with minimal tidal volume while keeping the lungs expanded with equal distribution of air in whole lung so less chances of barotrauma and volutrauma. Extra pressure which is not needed by the lung is dissipated through oral cavity and esophagus to the stomach. Few observational studies reported that extubation failure is better prevented with utilization of NHFOV.

For preterm neonates with RDS nHFOV compared with nCPAP showed better results in term of short duration of intervention, less chances of failure, low incidence of intraventricular hemorrhage, and other respiratory complications were almost equal.

A multicenter double, blinded, randomized controlled trial is under process for using non-invasive ventilation to prevent extubation failure. Another randomized controlled cross over trial performed in a small number of extreme preterm does showed better clearance of carbon dioxide with nHFOV compared with CPAP.

Retrospective cohort study published recently evaluating the use of non-invasive ventilation (nCPAP, SNIPPV and nHFOV) for preterm neonates with RDS, showed satisfactory outcomes with nHFOV with fewer babies requiring invasive ventilation.

A metanalysis of Randomized Controlled Trials of studies evaluating the use of nHFOV, nCPAP and biphasic CPAP; published recently showed nHFOV to be more effective as compared to other modes. The primary outcome of the RCT included in the meta analysis was decreased chances of intubation and better clearance of carbon dioxide.

In this study investigators will include inborn preterm neonates with no antenatal, perinatal risk factor or anomalies that can affect the outcome. Those babies who developed respiratory distress syndrome at birth and does not need early invasive ventilation will be recruited in study. Study will be conducted in almost 10 centers in Pakistan and Russia, total 1200 babies will be included from all centers. After all teaching and training regarding management strategies and equipment utilization. Recruited participants will be further divided in two arms, one in intervention arm (nHFOV) and other is control arm (Invasive Conventional) ventilation. Outcome will be assessed for respiratory support, surfactant requirement, duration of respiratory support, response to therapy and complications related to respiratory support.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 75190
      • Indus Hospital and Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 6 hours (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Inborn Preterm Neonates 26-34 weeks gestation admitted to NICU with diagnosis of RDS
• Babies who were initially started on High Flow Oxygen Therapy/nCPAP but unable to maintain saturation > 90% on fio2 of 40% in 1st 6 hours of life.
• Capillary PCO2 of > 70 or arterial PCO2 > 65 on two repeated sampling within 4 hours
• Neonates whose parents consented to participate.

Exclusion Criteria:

• All preterm babies who are below < 26 weeks above the 34 weeks of gestation
• Preterm neonates (26-34 weeks) with diagnosis of RDS requiring endotracheal intubation within Labor room/Operation Theater or within 1st hour of life for respiratory support.
• Preterm Neonates with the gestational age of 26-34 weeks, diagnosed as congenital pneumonia or sepsis.
• Patient with poor respiratory drive due to any reason neurological or central causes
• Diaphragmatic hernia or any other thoracic anomaly
• Pleural effusion unilateral or bilateral
• Congenital cystic pulmonary malformation.
• Neonates with underlying cyanotic heart disease.
• Neonates with acynotic heart disease causing pulmonary edema
• Neonates with cleft lip and cleft palate or any other surgical condition.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-invasive High Frequency Oscillatory Ventilation; Preterm babies (26-28 weeks) born with respiratory distress will be initially started on nCPAP with setting of flow 6-8 liter, PEEP 5-6, FiO2 21-40%. If fio2 requirefment more than 40%, surfactant will be given in first 2 hours of birth. If baby fails on CPAP then will be switched to nHFOV with below mentioned settings. Preterm born babies 28-34 weeks gestation with RDS, respiratory support will be started on Heated Humidified High Flow Oxygen therapy or nCPAP, if that fails then baby will be switched to NHFOV with frequency of 5-20 (300-1200 breathe/min), Amplitude of 1-10, flow1-17.5 liter/min, fiO2 21-100% and integrated pressure triggered sensitivity option.	Device: Non-invasive High Frequency Oscillatory Ventilation; We are planning to use (Medin-CNO) for non-invasive ventilation. This machine has option to deliver NHFOV with frequency of 5-20 (300-1200 breathe/min), Amplitude of 1-10, flow1-17.5 liter/min, fiO2 21-100% and integrated pressure triggered sensitivity option.; Other Names: Conventional Invasive Ventilation
Active Comparator: Conventional Invasive Ventilation; Preterm babies (26-28 weeks) born with respiratory distress will be initially started on nCPAP with setting of flow 6-8 liter, PEEP 5-6, FiO2 21-40%. If fio2 requirement more than 40%, surfactant will be given in first 2 hours of birth. If baby fails on CPAP then will be switched to nHFOV with below mentioned settings. Preterm born babies 28-34 weeks gestation with RDS, respiratory support will be started on Heated Humidified High Flow Oxygen therapy or nCPAP, if that fails then baby will be switched to invasive ventilation through endotracheal tube, mode will be selected as Synchronized Intermittent Mandatory ventilation (SIMV) with rate of 25-60 breath/min, flow of 8 liter, positive inspiratory pressure (PIP) of 14-25, Positive end expiratory pressure (PEEP) 4-5, fio2 of 21-40.	Device: Conventional Invasive Ventilation; Invasive ventilation will be started following endotracheal intubation, mode will be selected as Synchronized Intermittent Mandatory ventilation (SIMV) with rate of 25-60 breath/min, flow of 8 liter, positive inspiratory pressure (PIP) of 14-25, Positive end expiratory pressure (PEEP) 4-5, fio2 of 21-40.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Support Escalation	After starting with intervention or control group, baby will be monitored for further escalation of respiratory support like baby is Conventional Invasive Ventilation needs High frequency oscillatory ventilation. Baby started on NHFOV need invasive ventilation.	within first 24 hours of intervention
Oxygen Requirement	With assigned intervention or comparator, baby will be monitored for oxygen requirement comparing with baseline oxygen demand or > 40% of fractional Inspiratory oxygen.	Within first 24 hours
Weaning from Assigned respiratory support	Babies started on intervention or comparator will be monitored for weaning from respiratory support in hours after starting respiratory support.	within 1-2 weeks of respiratory support starting

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Surfactant Needed	Both groups will be compared for number of surfactant needed	within first 3 days of assignment
Respiratory Support Duration	Both groups will be compared for respiratory support duration in hours	up to 2 weeks
Complications related to respiratory support	Both groups will be compared for complication like pneumothorax, atelectasis, Collapse, pneumonia and bronchopulmonary dysplasia.	Within 1 week after respiratory support discontinuation
Complication related to prematurity	both groups will be compared for complication of prematurity like intraventricular hemorage, Patent Ductus Arteriosus, Intraventricular Hemorrhage, necrotizing enterocollitis, and nosocomial infection	Within 1week

Collaborators and Investigators

• Sponsor: Indus Hospital and Health Network
• Investigators: Principal Investigator: Syed RA Rehan Ali, FRCPCH, The Indus Hospital and Health Network

Publications and helpful links

General Publications

• Sankar MJ, Gupta N, Jain K, Agarwal R, Paul VK. Efficacy and safety of surfactant replacement therapy for preterm neonates with respiratory distress syndrome in low- and middle-income countries: a systematic review. J Perinatol. 2016 May;36 Suppl 1(Suppl 1):S36-48. doi: 10.1038/jp.2016.31.
• Wheeler CR, Smallwood CD. 2019 Year in Review: Neonatal Respiratory Support. Respir Care. 2020 May;65(5):693-704. doi: 10.4187/respcare.07720. Epub 2020 Mar 24.
• Boel L, Broad K, Chakraborty M. Non-invasive respiratory support in newborn infants. Paediatrics and Child Health. 2018;28(1):6-12.
• Fischer H. Efficacy and safety of non-invasive respiratory support in neonates. 2018.
• Batey N, Bustani P. Neonatal high-frequency oscillatory ventilation. Paediatrics and Child Health. 2020;30(4):149-53.
• Fischer HS, Bohlin K, Buhrer 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 Apr;174(4):465-71. doi: 10.1007/s00431-014-2419-y. Epub 2014 Sep 18.
• Huang J, Yuan L, Chen C. [Research advances in noninvasive high-frequency oscillatory ventilation in neonates]. Zhongguo Dang Dai Er Ke Za Zhi. 2017 May;19(5):607-611. doi: 10.7499/j.issn.1008-8830.2017.05.025. Chinese.
• Iranpour R, Armanian AM, Abedi AR, Farajzadegan Z. Nasal high-frequency oscillatory ventilation (nHFOV) versus nasal continuous positive airway pressure (NCPAP) as an initial therapy for respiratory distress syndrome (RDS) in preterm and near-term infants. BMJ Paediatr Open. 2019 Jul 14;3(1):e000443. doi: 10.1136/bmjpo-2019-000443. eCollection 2019.
• Shi Y, De Luca D; NASal OscillatioN post-Extubation (NASONE) study group. 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. BMC Pediatr. 2019 Jul 26;19(1):256. doi: 10.1186/s12887-019-1625-1.
• Bottino R, Pontiggia F, Ricci C, Gambacorta A, Paladini A, Chijenas V, Liubsys A, Navikiene J, Pliauckiene A, Mercadante D, Colnaghi M, Tana M, Tirone C, Lio A, Aurilia C, Pastorino R, Purcaro V, Maffei G, Liberatore P, Consigli C, Haass C, Lista G, Agosti M, Mosca F, Vento G. Nasal high-frequency oscillatory ventilation and CO2 removal: A randomized controlled crossover trial. Pediatr Pulmonol. 2018 Sep;53(9):1245-1251. doi: 10.1002/ppul.24120. Epub 2018 Jul 12.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 7, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: CPAP; RDS; Respiratory failure; nHFOV; Respiratory support
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: 2021_01_09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: In order to maintain data confidentiality, it will not be shared with other researcher

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No