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

Bronchopulmonary Dysplasia Clinical Trial

— FAST2  

Official title:

FAST TRIAL 2 - Fourier-transform Infrared Spectroscopy(FTIR) Guided Surfactant Therapy - RCT

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05638568
• Other study ID #: H-22007105 RCT Study
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: January 1, 2029

Study information

• Verified date: November 2023
• Source: Rigshospitalet, Denmark
• Contact: Christian Heiring
• Phone: +4535453545
• Email: christian.heiring[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Recently the investigators have developed a point of care test (LS-test) to measure surfactant as lecithin in gastric aspirates from preterm infants.

This test can be done immediately at delivery and potentially be used to guide surfactant treatment.

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.

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.

The investigators 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.

It has been demonstrated in clinical observational trials that this 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. It is believed 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 Validation study has been registered separately on clinicaltrials.gov (NCT05615428).

This registration concerns the FAST 2 RCT

Participants:

Preterm newborn infants with gestational age at birth of ≤ 29+6 weeks who have not received prophylactic surfactant.

Intervention:

Surfactant treatment guided by fast determination of the L/S-ratio in a fresh gastric aspirate (GAS) obtained at birth, measured by Fourier Transform Mid-infrared Spectroscopy as a POC test.

Comparison:

Standard rescue surfactant treatment based on clinical criteria defined by the European Consensus Guidelines on the management of Respiratory Distress Syndrome

Outcome:

Infants surviving without moderate to severe BPD assessed at 36 weeks post menstrual age as per a modified NIH definition

The primary outcome is a composite of survival without moderate to severe BPD, defined as per a modified "NIH definition"

The primary objective is to compare the rate of survival without moderate to severe BPD between 2 groups:

• L/S guided treatment of surfactant deficiency with exogenous surfactant (intervention group) vs.

• Standard treatment of surfactant deficiency (comparison).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 380
• Est. completion date: January 1, 2029
• Est. primary completion date: July 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 45 Minutes

Eligibility

Inclusion Criteria:

• GA = 29+6, inborn at a participating centre

• Age less than 45 minutes as GAS must be sampled within 45 minutes from delivery.

Exclusion Criteria:

• Treated with surfactant before randomisation 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

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Surfactant Deficiency Syndrome Neonatal
• Syndrome

Intervention

Diagnostic Test:
• LS test
If the LS test indicated surfactant deficiency based on the cut off ratio early surfactant treatment will be done for patients in the intervention group If the LS test indicated no surfactant deficiency routine surfactant treatment will be done as per European RDS guidelines based on oxygen requirement (FiO2 > 0.30)

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus Universtity Hospital	Aarhus
Denmark	Department of Neonatology, Rigshospitalet	Copenhagen
Denmark	Odense University Hospital	Odense

Sponsors (5)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Aalborg University Hospital, Aarhus University Hospital, Holbaek Sygehus, Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival without moderate to severe bronchopulmonary dysplasia (BPD)	BPD is defined as per a modified "NIH definition" in which any degree of respiratory support for at least 28 days is considered equal to the need for oxygen: Treatment with oxygen > 21% or any degree of respiratory support for a least 28 days plus; Need for treatment with oxygen > 21% or any degree of respiratory support at PMA 36 weeks or at discharge, whichever comes first.; Definitions: Moderate BPD is defined as treatment with oxygen > 21% or any degree of respiratory support for a least 28 days plus need of supplemental oxygen from >21% to < 30% (as low flow O2) at 36+0 weeks PMA; Severe BPD is defined as treatment with oxygen > 21% or any degree of respiratory support for a least 28 days plus need of > 30% oxygen and/or continuous need for any level of respiratory support providing positive airway pressure (nHFT, nCPAP, NIV or mechanical ventilation)	at 36 weeks PMA or discharge withever comes first
Secondary	mortality	assessed at discharged	From date of birth until the date of death if this happens before discharge
Secondary	Bronchopulmonary dysplasia	BPD is defined as per a modified "NIH definition" in which any degree of respiratory support for at least 28 days is considered equal to the need for oxygen: Treatment with oxygen > 21% or any degree of respiratory support for a least 28 days plus; Need for treatment with oxygen > 21% or any degree of respiratory support at PMA 36 weeks or at discharge, whichever comes first.; Definitions: Moderate BPD is defined as treatment with oxygen > 21% or any degree of respiratory support for a least 28 days plus need of supplemental oxygen from >21% to < 30% (as low flow O2) at 36+0 weeks PMA; Severe BPD is defined as treatment with oxygen > 21% or any degree of respiratory support for a least 28 days plus need of > 30% oxygen and/or continuous need for any level of respiratory support providing positive airway pressure (nHFT, nCPAP, NIV or mechanical ventilation)	at 36 weeks PMA or discharge withever comes first
Secondary	LS-ratio	POC measurement using FTIR Spectroscopy	72 hours
Secondary	Nectrotizing enterocolitis	According to Bell classification/AXR	From date of birth to 44 weeks of gestational age (usually around 18 weeks)
Secondary	Spontaneous intestinal perforation	As diagnosed on AXR	From date of birth to 44 weeks of gestational age (usually around 18 weeks)
Secondary	Intraventricular hemorhage	According to Papile classification	From date of birth to 44 weeks of gestational age (usually around 18 weeks)
Secondary	Airleak	Assessed on CXR or lung ultrasound	From date of birth to 44 weeks of gestational age (usually around 18 weeks)
Secondary	surfactant treatment,	from medical record	72 hours
Secondary	surfactant treatmentdose,	from medical record	72 hours
Secondary	number of surfactant treatments,	from medical record	72 hours
Secondary	timing surfactant treatments,	from medical record	72 hours
Secondary	gastric aspirate obtained	from medical record	72 hours
Secondary	gastric aspirate analyzed	from medical record	72 hours