Infant Forced Oscillations Technique (iFOT)

Respiratory Disease Clinical Trial

— iFOT  

Official title:

Application of Forced Oscillation Technique in Infancy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04697251
• Other study ID #: 28292/20201103
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2021
• Est. completion date: March 2023

Study information

• Verified date: April 2021
• Source: University of Patras
• Contact: Sotirios Fouzas, MD, PhD
• Phone: 6944510047
• Email: sfouzas[@]upatras.gr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is the implementation of Forced Oscillations Technique (FOT) in newborns and small infants using a novel commercially available device.

The objective is to assess the feasibility of the method, provide normative data for the first months of life and describe short- and long-term changes in neonatal respiratory disorders.

The study population will consist of term and preterm newborns admitted to the Neonatal Intensive Care Unit (NICU) or the Well-Baby Nursery of the University Hospital of Patras, Greece. It is estimated that 200 full-term and 150 preterm newborns will be enrolled during a period of 36 months (March 2021 - September 2022).

Measurements will be performed using the TremoFlo N-100 via a face mask, with the infant in the supine position during natural sleep. At least 3 technically acceptable measurements (duration 10s each) will be obtained, as follows:

• Healthy full-term neonates: postnatal days 1, 2, 3 and at discharge

• Preterm neonates: NICU admission, postnatal days 1, 2 and 3, and on the first day of each additional gestational week until discharge

All participants will be also measured at the age of 3, 6 and 12 months.

Description:

INTRODUCTION Pulmonary function testing during early infancy requires sophisticated equipment, specialized personnel and proper patient's preparation. As a result, lung function testing in newborns and small infants is limited to few highly specialized centers.

The forced oscillations technique (FOT) uses complex pressure signals generated by an external device at the airway opening. The pressure waves are transmitted through the airway tree during tidal breathing and force the anatomical structures of the respiratory system to oscillate. From subsequent pressure and flow signal analysis, the total resistance (Rrs) and reactance (Xrs) of the respiratory system are calculated. The latter relates mainly to the elastic properties of the lung parenchyma and the inertia of the column of air in the airways. Both Rrs and Xrs depend on the frequency of oscillation; lower frequencies (range 5-10Hz) provide information on the mechanical properties of smaller airways and vice versa. FOT measurements can be performed fast (usually in less than 30 s), at the bedside, and do not require patient's cooperation. Therefore, FOT is being viewed as an attractive and promising pulmonary function technique for young infants and newborns.

To date, the introduction of infant FOT in routine clinical practice has been limited due to lack of suitable devices and normative data. Studies based on in-build FOT equipment have shown that the application of the method in small infants is feasible. A recent study, in which a modified commercially available device (Tremoflo C-100, THORASYS Thoracic Medical Systems Inc. Montreal, Canada) was used, also supports the feasibility of the method.

OBJECTIVE The aim of this study is the implementation of FOT in newborns and small infants using a novel commercially available device (Tremoflo N-100, THORASYS), specifically released for this age range.

Our objectives are: a) to assess the feasibility of the method and the repeatability of FOT measurements in newborns and small infants, b) to provide normative data for the first months of life in relation to various parameters (e.g. gender, age, somatometrics, etc) and, c) to describe short- and long-term and Rrs and Xrs changes in neonatal respiratory disease (e.g. respiratory distress syndrome, bronchopulmonary dysplasia, etc).

METHODS Population The study population will consist of term and preterm newborns admitted to the Neonatal Intensive Care Unit (NICU) or the Well-Baby Nursery of the University Hospital of Patras, Greece. It is estimated that 200 full-term and 150 preterm newborns will be enrolled during a period of 36 months (March 2021 - September 2022).

The parents of all infants will provide written informed consent prior to enrollment. The study has been approved by the Research and Ethics Committee of the hospital (decision no. 451/12.11.2020).

Measurements Measurements will be performed using the TremoFlo N-100, at bedside, with the infant in the supine position during quiet natural sleep. The device will be calibrated daily, according to manufacturer's instructions. After proper cleaning and decontamination, the face mask of the device will be preheated at 37oC (to avoid awakening) and will be placed on infant's face. The duration of each measurement will be predetermined at 10 s. At least 3 technically acceptable measurements will be performed per infant, with 30 s intervals between them. The validity of each measurement will be assessed according to the coherence function (automatically determined by the operating system of the device).

Protocol

FOT measurements will be scheduled according to the target population, as follows:

• In healthy full-term neonates, measurements will be obtained on postnatal days 1, 2, 3 and at discharge. Parents will be asked and scheduled to repeat testing at the age of 3, 6 and 12 months.

• In preterm neonates without respiratory disease, measurements will be performed on NICU admission, on postnatal days 1, 2 and 3, and on the first day of each additional gestational week until discharge. For example, a preterm neonate with gestational age 331/7, will be measured at 331/7, 332/7, 333/7, 334/7, 34, 35, 36, etc. Parents of preterm newborns will be also asked and scheduled to repeat testing at the age of 3, 6 and 12 months.

• In preterm neonates with respiratory distress syndrome (RDS) the measurements will be obtained on NICU admission and at 6 and 12 hours after surfactant administration. Thereafter, the same protocol with preterm neonates without respiratory disease will be applied. In mechanically ventilated infants the measurements will be performed via the endotracheal tube, but only if their clinical condition permits FOT testing. In such cases, the device will be calibrated in advance using an endotracheal tube of the same internal diameter, material and length as that positioned on the neonate.

EXPECTED RESULTS AND BENEFITS The study is expected to confirm the feasibility of FOT in newborns and small infants (in NICU or outpatient settings) and, most important, to reveal a series of technical/practical details that may improve the applicability of the method in clinical practice. Finally, the study will provide normative data for this age range, and will assess Rrs and Xrs changes in various respiratory disorders of the neonatal period and early infancy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: March 2023
• Est. primary completion date: September 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 12 Months

Eligibility

Inclusion Criteria:

• Newborns cared for in the NICU and well-baby nursery of the University Hospital of Patras, Greece.

• Parental written informed consent.

Exclusion Criteria:

• Major respiratory, cardiovascular or other condition that does not permit FOT measurements at the predetermined time points.

• Any infectious disorder with increased risk of contamination.

• Orofacial anomalies (e.g. genetic syndromes) that do not permit proper application of the face mask.

Related Conditions & MeSH terms

• Infant, Newborn, Disease
• Infant, Newborn, Diseases
• Respiration Disorders
• Respiratory Disease
• Respiratory Function Tests
• Respiratory Tract Diseases

Intervention

Diagnostic Test:
• FOT measurements in newborns and small infants
Measurements will be performed using the device TremoFlo N-100, at bedside, with the infant in the supine position during quiet natural sleep. After proper cleaning and decontamination, the face mask of the device will be preheated at 37oC (to avoid awakening) and will be placed on infant's face. The duration of each measurement will be predetermined at 10 s. At least 3 technically acceptable measurements will be performed per infant, with 30 s intervals between them. The validity of each measurement will be assessed according to the coherence function (automatically determined by the operating system of the device).

Locations

Country	Name	City	State
Greece	Neonatal Intensive Care Unit, University Hospital of Patras	Patras
Greece	Well-baby nursery, Department of Pediatrics, University Hospital of Patras	Patras

Sponsors (1)

Lead Sponsor	Collaborator
University of Patras

Country where clinical trial is conducted

Greece, 

References & Publications (4)

Gray DM, Czovek D, McMillan L, Turkovic L, Stadler JAM, Vanker A, Radics BL, Gingl Z, Hall GL, Sly PD, Zar HJ, Hantos Z. Intra-breath measures of respiratory mechanics in healthy African infants detect risk of respiratory illness in early life. Eur Respir J. 2019 Jan 31;53(2). pii: 1800998. doi: 10.1183/13993003.00998-2018. Print 2019 Feb. — View Citation

Hantos Z, Czövek D, Gyurkovits Z, Szabó H, Maár BA, Radics B, Virág K, Makan G, Orvos H, Gingl Z, Sly PD. Assessment of respiratory mechanics with forced oscillations in healthy newborns. Pediatr Pulmonol. 2015 Apr;50(4):344-52. doi: 10.1002/ppul.23103. Epub 2014 Aug 25. — View Citation

Klinger AP, Travers CP, Martin A, Kuo HC, Alishlash AS, Harris WT, Carlo WA, Ambalavanan N. Non-invasive forced oscillometry to quantify respiratory mechanics in term neonates. Pediatr Res. 2020 Aug;88(2):293-299. doi: 10.1038/s41390-020-0751-7. Epub 2020 Jan 14. — View Citation

Skylogianni E, Douros K, Anthracopoulos MB, Fouzas S. The Forced Oscillation Technique in Paediatric Respiratory Practice. Paediatr Respir Rev. 2016 Mar;18:46-51. doi: 10.1016/j.prrv.2015.11.001. Epub 2015 Nov 10. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory resistance (Rrs) - Term newborns	Rrs at multiple frequencies (FOT) in term infants	Postnatal day 1.
Primary	Respiratory resistance (Rrs) - Term newborns	Rrs at multiple frequencies (FOT) in term infants	Postnatal day 2.
Primary	Respiratory resistance (Rrs) - Term newborns	Rrs at multiple frequencies (FOT) in term infants	Postnatal day 3.
Primary	Respiratory resistance (Rrs) - Term newborns	Rrs at multiple frequencies (FOT) in term infants	On the day of discharge.
Primary	Respiratory reactance (Xrs) - Term newborns	Xrs at multiple frequencies (FOT) in term infants	Postnatal day 1.
Primary	Respiratory reactance (Xrs) - Term newborns	Xrs at multiple frequencies (FOT) in term infants	Postnatal day 2.
Primary	Respiratory reactance (Xrs) - Term newborns	Xrs at multiple frequencies (FOT) in term infants	Postnatal day 3.
Primary	Respiratory reactance (Xrs) - Term newborns	Xrs at multiple frequencies (FOT) in term infants	On the day of discharge
Primary	Respiratory resistance (Rrs) - Preterm newborns	Rrs at multiple frequencies (FOT) in preterm infants	At NICU admission (within the first 2 hours).
Primary	Respiratory resistance (Rrs) - Preterm newborns	Rrs at multiple frequencies (FOT) in preterm infants	Postnatal day 1.
Primary	Respiratory resistance (Rrs) - Preterm newborns	Rrs at multiple frequencies (FOT) in preterm infants	Postnatal day 2.
Primary	Respiratory resistance (Rrs) - Preterm newborns	Rrs at multiple frequencies (FOT) in preterm infants	Postnatal day 3.
Primary	Respiratory resistance (Rrs) - Preterm newborns	Rrs at multiple frequencies (FOT) in preterm infants	On the first day of each additional week until 36 weeks post-conceptional age.
Primary	Respiratory resistance (Rrs) - Preterm newborns	Rrs at multiple frequencies (FOT) in preterm infants	On the day of discharge.
Primary	Respiratory reactance (Xrs) - Preterm newborns	Xrs at multiple frequencies (FOT) in preterm infants	At NICU admission (within the first 2 hours).
Primary	Respiratory reactance (Xrs) - Preterm newborns	Xrs at multiple frequencies (FOT) in preterm infants	On postnatal day 1.
Primary	Respiratory reactance (Xrs) - Preterm newborns	Xrs at multiple frequencies (FOT) in preterm infants	On postnatal day 2.
Primary	Respiratory reactance (Xrs) - Preterm newborns	Xrs at multiple frequencies (FOT) in preterm infants	On postnatal day 3.
Primary	Respiratory reactance (Xrs) - Preterm newborns	Xrs at multiple frequencies (FOT) in preterm infants	On the first day of each additional week until 36 weeks post-conceptional age.
Primary	Respiratory reactance (Xrs) - Preterm newborns	Xrs at multiple frequencies (FOT) in preterm infants	On the day of discharge.
Primary	Respiratory resistance (Rrs) - Infancy	Rrs at multiple frequencies (FOT) during infancy	At the age of 3 months (+/- 1 week)
Primary	Respiratory resistance (Rrs) - Infancy	Rrs at multiple frequencies (FOT) during infancy	At the age of 6 months (+/- 1 week)
Primary	Respiratory resistance (Rrs) - Infancy	Rrs at multiple frequencies (FOT) during infancy	At the age of 12 months (+/- 2 weeks)
Primary	Respiratory reactance (Xrs) - Infancy	Xrs at multiple frequencies (FOT) during infancy	At the age of 3 months (+/- 1 week)
Primary	Respiratory reactance (Xrs) - Infancy	Xrs at multiple frequencies (FOT) during infancy	At the age of 6 months (+/- 1 week)
Primary	Respiratory reactance (Xrs) - Infancy	Xrs at multiple frequencies (FOT) during infancy	At the age of 12 months (+/- 2 weeks)