Clinical trial NCT05615428: Fast Assessment of Surfactant Deficiency in Preterm Infants to Speed up Treatment - Validation Study
Official title: FAST TRIAL 2 -Fourier-transform Infrared Spectroscopy(FTIR)Guided Surfactant Therapy - Validation Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Surfactant Deficiency Syndrome Neonatal
Respiratory Distress Syndrome in Premature Infant
Keywords: surfactant replacement therapy
surfactant assay
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
name: Aalborg University Hospital
name: Aarhus University Hospital
name: Holbaek Sygehus
First posted: 2022-11-14
Enrollment: 68
Sex: ALL
Maximum age (years): 45
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Preterm newborn babies that have gastric secretions sampled before 45 minutes of age.

Brief summary: The aim is to re-validate a FTIR spectroscopy test for measuring lung maturity/Respiratory Distress Syndrome (RDS) before conducting a RCT using this test to guide surfactant treatment of preterm infants.

The test has been validated previously (NCT03235882) but needs re-validation due to continued improvement in accuracy and since the test is now developed into a Point of Care test (POC-test).

The purpose is to accurately predict RDS using Lecithin/Sphingomyelin ratio (L/S ratio determined by a rapid FTIR in a newly developed point of care test (POC-test) on fresh gastric aspirates using retrospective analysis.

The FAST 2 Validation Study is a part of the FAST 2 Trial consisting of a validation study and a subsequent randomized clinical trial, that will be registered separately on clinicaltrials.gov (NTC XXXXXXXXX)

Detailed description: Treatment of respiratory distress syndrome (RDS) has evolved greatly over the past three decades. Major advances in treatment include antenatal steroids, early nasal continuous positive airway pressure (nCPAP) combined with early rescue surfactant replacement strategies such as Intubation Surfactant Extubation (INSURE) and Less Invasive Surfactant Administration (LISA), together with use of lung protective ventilation and overall reduced use of mechanical ventilation. However, RDS and bronchopulmonary dysplasia (BPD) are still major causes of mortality and morbidity in premature infants. To improve the outcome, very early treatment with surfactant is necessary. However, only about half of infants with a gestational age (GA) below 30 weeks need surfactant treatment and prophylactic surfactant treatment increases the combined mortality and incidence of BPD contrary to selective rescue surfactant treatment. Therefore, there is a need for a rapid test to guide early targeted surfactant treatment.

We have recently developed a new test of lung maturity based on measuring the lecithin sphingomyelin ratio (L/S) in fresh gastric aspirates (GAS) from newborn preterm infants using mid-red Fourier Transform Infrared spectroscopy (FTIR). The sphingomyelin concentration in amniotic fluid and accordingly in GAS is relatively constant during the pregnancy, whereas the lecithin (or dipalmitoylphosphatidylcholine (DPPC), the lung surfactant phospholipid with the highest surface activity) concentration increases with the lung maturation.

We have demonstrated in clinical observational trials that our laboratory based L/S-test predicts development of RDS when measured immediately at delivery (FAST 1 Trial).

The L/S-test has now been developed into an easy-to-use Point of Care (POC) test for bedside use that expresses the L/S ratio in approximately 10 minutes. We believe this new POC test can be used to guide surfactant therapy, enabling very early rescue treatment, potentially even before symptoms occur.

To obtain evidence-based knowledge on harms and benefit of surfactant therapy guided by the L/S test, a randomized clinical trial with relevant clinical short-and long-term outcomes needs to be performed, which is why the FAST 2 Trial has been designed.

During design and development of the FAST 2 Trial protocol extensive engineering work has been conducted towards building a fully automated L/S POC Device (AIMI 1.0/2.0) from the prototypes in the first L/S studies (including FAST 1 Trial).

During this process the accuracy of the L/S algorithm has been improved through machine learning and use of artificial intelligence. Consequently, the previously defined cut-off ratio from the FAST 1 Trial needs to be re-validated using the L/S POC Device in a new population of preterm infants.

The FAST 2 Trial therefore consists of two individual studies starting with the FAST 2 Validation Study which will followed by the FAST 2 Randomized Clinical Trial (FAST 2 RCT) once completed. The FAST 2 RCT will be registered at clinicaltrials.gov separately.

The objective of FAST 2 Validation study is:

In preterm infants with gestational age at birth of ≤ 29+6 weeks less than 45 minutes of age who have not received surfactant prior to the measurenent, we aim to:

• measure L/S-ratio in fresh GAS using the AIMI 1.0/2.0 L/S POC Device

and compare the L/S-ratio by: • the need for surfactant treatment

with the aim to:

• validate the previously defined optimal cut-off L/S-ratio for surfactant treatment and to determine if the cut-off L/S ratio needs to be adjusted before starting FAST 2 RCT

Eligibility criteria: Inclusion Criteria:

GA ≤29+6, inborn at a participating centre Age less than 45 minutes as gastric aspirate must be sampled within 45 minutes from delivery.

Exclusion criteria:

Treated with surfactant beforerandomisation and obtaining gastric aspirates

Diagnosis of major malformations (major congenital heart defects, congenital diaphragmatic hernia, gastroschisis/omphalocele, pulmonary abnormalities including pulmonary hypoplasia and trachea-oesophageal fistula

Antenatal suspicion of significant oligohydramnios and lung hypoplasia

Any intrauterine intervention except if done for genetic testing

Primary outcomes:
measure: LS-ratio cut-off
timeFrame: 5 days
Secondary outcomes:
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Christian Heiring
role: PRINCIPAL_INVESTIGATOR
References: