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

Primary Purpose

Respiratory Distress Syndrome in Premature Infant

Status
Not yet recruiting
Phase
Not Applicable
Locations
Pakistan
Study Type
Interventional
Intervention
Non-invasive High Frequency Oscillatory Ventilation
Conventional Invasive Ventilation
Sponsored by
Indus Hospital and Health Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Respiratory Distress Syndrome in Premature Infant focused on measuring nHFOV, RDS, CPAP, Respiratory failure, Respiratory support

Eligibility Criteria

1 Hour - 6 Hours (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Indus Hospital and Health Network

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Non-invasive High Frequency Oscillatory Ventilation

Conventional Invasive Ventilation

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Number of Surfactant Needed
Both groups will be compared for number of surfactant needed
Respiratory Support Duration
Both groups will be compared for respiratory support duration in hours
Complications related to respiratory support
Both groups will be compared for complication like pneumothorax, atelectasis, Collapse, pneumonia and bronchopulmonary dysplasia.
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

Full Information

First Posted
March 17, 2021
Last Updated
June 3, 2021
Sponsor
Indus Hospital and Health Network
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1. Study Identification

Unique Protocol Identification Number
NCT04914715
Brief Title
nHFOV Versus Invasive Conventional Ventilation for Preterm Neonates With Respiratory Distress Syndrome
Acronym
nHFOV
Official Title
Effectiveness of Non-invasive High Frequency Oscillatory Ventilation (nHFOV) Versus Invasive Conventional Ventilation for Preterm Neonates With Respiratory Distress Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2021 (Anticipated)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indus Hospital and Health Network

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Distress Syndrome in Premature Infant
Keywords
nHFOV, RDS, CPAP, Respiratory failure, Respiratory support

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomization will be done via random allocation software 1.0.0. This software produces as its output a sequence of allocation based on selected type. Considering 2 groups with equal sample size, a simple random allocation list will be generated using block randomization. The list will be used to create Sequentially Numbered, Opaque, Sealed Envelopes (SNOSE) to assure allocation concealment. The process of randomization will be conducted by Indus Hospital Research Centre (IHRC) independently.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Non-invasive High Frequency Oscillatory Ventilation
Arm Type
Experimental
Arm Description
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.
Arm Title
Conventional Invasive Ventilation
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Non-invasive High Frequency Oscillatory Ventilation
Other Intervention Name(s)
Conventional Invasive Ventilation
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Conventional Invasive Ventilation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Respiratory Support Escalation
Description
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.
Time Frame
within first 24 hours of intervention
Title
Oxygen Requirement
Description
With assigned intervention or comparator, baby will be monitored for oxygen requirement comparing with baseline oxygen demand or > 40% of fractional Inspiratory oxygen.
Time Frame
Within first 24 hours
Title
Weaning from Assigned respiratory support
Description
Babies started on intervention or comparator will be monitored for weaning from respiratory support in hours after starting respiratory support.
Time Frame
within 1-2 weeks of respiratory support starting
Secondary Outcome Measure Information:
Title
Number of Surfactant Needed
Description
Both groups will be compared for number of surfactant needed
Time Frame
within first 3 days of assignment
Title
Respiratory Support Duration
Description
Both groups will be compared for respiratory support duration in hours
Time Frame
up to 2 weeks
Title
Complications related to respiratory support
Description
Both groups will be compared for complication like pneumothorax, atelectasis, Collapse, pneumonia and bronchopulmonary dysplasia.
Time Frame
Within 1 week after respiratory support discontinuation
Title
Complication related to prematurity
Description
both groups will be compared for complication of prematurity like intraventricular hemorage, Patent Ductus Arteriosus, Intraventricular Hemorrhage, necrotizing enterocollitis, and nosocomial infection
Time Frame
Within 1week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Hour
Maximum Age & Unit of Time
6 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vikram VK Kessani, FCPS
Phone
00922135110447
Ext
2838
Email
vikram.kumar@tih.org.pk
First Name & Middle Initial & Last Name or Official Title & Degree
Anum AR Rahim, MSC
Phone
00922135112709
Ext
2415
Email
Anum.Rahim@tih.org.pk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Syed RA Rehan Ali, FRCPCH
Organizational Affiliation
The Indus Hospital and Health Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indus Hospital and Health Network
City
Karachi
State/Province
Sindh
ZIP/Postal Code
75190
Country
Pakistan
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vikram VK Kumar, FCPS
Phone
00922135110447
Ext
2838
Email
vikram.kumar@tih.org.pk
First Name & Middle Initial & Last Name & Degree
Anum AR Rahim, MSC
Phone
00922135112709
Ext
2415
Email
anum.rahim@tih.org.pk

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
In order to maintain data confidentiality, it will not be shared with other researcher
Citations:
PubMed Identifier
27109091
Citation
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.
Results Reference
background
PubMed Identifier
32209710
Citation
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.
Results Reference
background
Citation
Boel L, Broad K, Chakraborty M. Non-invasive respiratory support in newborn infants. Paediatrics and Child Health. 2018;28(1):6-12.
Results Reference
background
Citation
Fischer H. Efficacy and safety of non-invasive respiratory support in neonates. 2018.
Results Reference
background
Citation
Batey N, Bustani P. Neonatal high-frequency oscillatory ventilation. Paediatrics and Child Health. 2020;30(4):149-53.
Results Reference
background
PubMed Identifier
25227281
Citation
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.
Results Reference
background
PubMed Identifier
28506358
Citation
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.
Results Reference
background
PubMed Identifier
31414062
Citation
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.
Results Reference
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PubMed Identifier
31349833
Citation
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.
Results Reference
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PubMed Identifier
29999596
Citation
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.
Results Reference
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nHFOV Versus Invasive Conventional Ventilation for Preterm Neonates With Respiratory Distress Syndrome

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