Fast Assessment of Surfactant Deficiency in Preterm Infants to Speed up Treatment - Validation Study

NCT ID: NCT05615428

Last Updated: 2025-05-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 68 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-16
• Study Completion Date: 2023-08-01

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

Conditions

Surfactant Deficiency Syndrome Neonatal; Respiratory Distress Syndrome in Premature Infant

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

observational group

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

LS-ratio

Intervention Type: DIAGNOSTIC_TEST

Included infants will have a gastric aspirate sampled via an NG tube at birth. This sample will be analyzed to determine the LS-ratio The LS-ratio will retrospectively be compared to RDS development and need for surfactant treatment to establish the cut-off ratio for LS-ratio with respect to surfactant treatment.

Interventions

LS-ratio

Included infants will have a gastric aspirate sampled via an NG tube at birth. This sample will be analyzed to determine the LS-ratio The LS-ratio will retrospectively be compared to RDS development and need for surfactant treatment to establish the cut-off ratio for LS-ratio with respect to surfactant treatment.

Intervention Type: DIAGNOSTIC_TEST

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

• Maximum Eligible Age: 45 Minutes
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Odense University Hospital

OTHER

Sponsor Role: collaborator

Aalborg University Hospital

OTHER

Sponsor Role: collaborator

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

Holbaek Sygehus

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Christian Heiring

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christian Heiring

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Locations

Aalborg University Hospital

Aalborg, , Denmark

Aarhus University Hospital

Aarhus, , Denmark

Odense University Hospital

Odense, , Denmark

Countries

Denmark

Other Identifiers

H-22007105 Validation Study

Identifier Type: -

Identifier Source: org_study_id