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