Clinical trial NCT04697251: Infant Forced Oscillations Technique (iFOT)
Official title: Application of Forced Oscillation Technique in Infancy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Respiratory Function Tests
Respiratory Disease
Infant, Newborn, Disease
Lead sponsor: University of Patras
Sponsor class: OTHER
First posted: 2021-01-06
Enrollment: 350
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Respiratory resistance (Rrs) - Term newborns
timeFrame: Postnatal day 1.
measure: Respiratory resistance (Rrs) - Term newborns
timeFrame: Postnatal day 2.
measure: Respiratory resistance (Rrs) - Term newborns
timeFrame: Postnatal day 3.
measure: Respiratory resistance (Rrs) - Term newborns
timeFrame: On the day of discharge.
measure: Respiratory reactance (Xrs) - Term newborns
timeFrame: Postnatal day 1.
measure: Respiratory reactance (Xrs) - Term newborns
timeFrame: Postnatal day 2.
measure: Respiratory reactance (Xrs) - Term newborns
timeFrame: Postnatal day 3.
measure: Respiratory reactance (Xrs) - Term newborns
timeFrame: On the day of discharge
measure: Respiratory resistance (Rrs) - Preterm newborns
timeFrame: At NICU admission (within the first 2 hours).
measure: Respiratory resistance (Rrs) - Preterm newborns
timeFrame: Postnatal day 1.
measure: Respiratory resistance (Rrs) - Preterm newborns
timeFrame: Postnatal day 2.
measure: Respiratory resistance (Rrs) - Preterm newborns
timeFrame: Postnatal day 3.
measure: Respiratory resistance (Rrs) - Preterm newborns
timeFrame: On the first day of each additional week until 36 weeks post-conceptional age.
measure: Respiratory resistance (Rrs) - Preterm newborns
timeFrame: On the day of discharge.
measure: Respiratory reactance (Xrs) - Preterm newborns
timeFrame: At NICU admission (within the first 2 hours).
measure: Respiratory reactance (Xrs) - Preterm newborns
timeFrame: On postnatal day 1.
measure: Respiratory reactance (Xrs) - Preterm newborns
timeFrame: On postnatal day 2.
measure: Respiratory reactance (Xrs) - Preterm newborns
timeFrame: On postnatal day 3.
measure: Respiratory reactance (Xrs) - Preterm newborns
timeFrame: On the first day of each additional week until 36 weeks post-conceptional age.
measure: Respiratory reactance (Xrs) - Preterm newborns
timeFrame: On the day of discharge.
measure: Respiratory resistance (Rrs) - Infancy
timeFrame: At the age of 3 months (+/- 1 week)
measure: Respiratory resistance (Rrs) - Infancy
timeFrame: At the age of 6 months (+/- 1 week)
measure: Respiratory resistance (Rrs) - Infancy
timeFrame: At the age of 12 months (+/- 2 weeks)
measure: Respiratory reactance (Xrs) - Infancy
timeFrame: At the age of 3 months (+/- 1 week)
measure: Respiratory reactance (Xrs) - Infancy
timeFrame: At the age of 6 months (+/- 1 week)
measure: Respiratory reactance (Xrs) - Infancy
timeFrame: At the age of 12 months (+/- 2 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Patras
country: Greece
facility: Neonatal Intensive Care Unit, University Hospital of Patras
city: Patras
country: Greece
facility: Well-baby nursery, Department of Pediatrics, University Hospital of Patras
Study officials:
affiliation: University of Patras
name: Sotirios Fouzas
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Hantos Z, Czovek D, Gyurkovits Z, Szabo H, Maar BA, Radics B, Virag 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.
citation: 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):1800998. doi: 10.1183/13993003.00998-2018. Print 2019 Feb.
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.