None listed
Conditions
Brief summary
Patency of the ductus arteriosus in preterm infants is dictated primarily by Prostaglandin E2 (PGE2) and the non-steroidal anti-inflammatory medications that have long been used to promote ductal closure act by reducing prostaglandin production through cyclooxygenase enzyme inhibition. There is evidence that corticosteroids may also promote ductal closure through at least two mechanisms that impact PGE2 levels. This includes increasing phospholipase A2 inhibitor production with resultant decreased PGE2 synthesis and inhibition of 15-PGHD with resultant increased PGE2 break-down. More importantly, the vast majority of randomised controlled trials evaluating administration of early systemic, inhaled, or intra-tracheal corticosteroids to very preterm infants have found decreased rates of patent ductus arteriosus (PDA) diagnosis, medical treatment of PDA and/or surgical ductal ligation in exposed infants, suggesting a possible effect on early ductus arteriosus closure. What remains unclear is whether the mechanism behind decreased rates of PDA diagnosis and treatment is a direct effect due to corticosteroids promoting early ductus arteriosus closure, or an indirect effect of corticosteroids providing a respiratory benefit that results in clinicians being less inclined to pursue or treat a PDA. The PLUSS Trial is a multicentre, two-arm, parallel, double-blind randomised clinical trial designed to evaluate the effect of early intra-tracheal budesonide (a corticosteroid) mixed with surfactant on survival without BPD in extremely preterm infants born <28 weeks’ gestation (n = 1060). The PLUSS-HEARTS sub-study will utilise the double-blind randomised methodology of PLUSS in select participating sites to measure rates of early ductus arteriosus closure following exposure to intra-tracheal corticosteroids, compared with no exposure. This will hopefully shed light on the true effect of intratracheal corticosteroids on PDA diagnosis or treatment in this high-risk patient population.
Interventions
Infants enrolled in this sub-study will receive interventions as described in the parent study PLUSS trial (ACTRN12617000322336).
Infants enrolled in PLUSS- HEARTs will undergo a rapid cardiac ultrasound at 48-72 hours after birth. This examination is anticipated to take approximately 5 minutes. At day 6-7 of life infants will undergo a focussed cardiac ultrasound with measures of cardiac function, pulmonary circulation and measures of systemic circulation. This second longer examination is e
Infants enrolled in this sub-study will receive interventions as described in the parent study PLUSS trial (ACTRN12617000322336). Infants enrolled in PLUSS- HEARTs will undergo a rapid cardiac ultrasound at 48-72 hours after birth. This examination is anticipated to take approximately 5 minutes. At day 6-7 of life infants will undergo a focussed cardiac ultrasound with measures of cardiac function, pulmonary circulation and measures of systemic circulation. This second longer examination is expected to take approximately 10-15 minutes .
Sponsors
Melbourne Children's Trials Centre
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
0 to 48 Hours
Healthy volunteers
No
Inclusion criteria
To be eligible for PLUSS-HEARTS, infants must be enrolled in the PLUSS trial (ACTRN12617000322336) and meet all inclusion and no exclusion criteria. Additional inclusion criteria for the PLUSS-HEARTS trial include: 1. Infant less than 48 hours of age 2. Infants receiving mechanical ventilation via an endotracheal tube or non-invasive respiratory support including CPAP, NIPPV or nasal high flow, and a clinical decision to treat the infant with exogenous surfactant (first or subsequent dose)
Exclusion criteria
Criteria for exclusion from the PLUSS Trial (ACTRN12617000322336):includes (any of the following): 1. Prior treatment with corticosteroids for the prevention of lung disease (inhaled, nebulised, intra-tracheal, or systemic) 2. Infant is considered non-viable or is not going to be admitted to intensive care 3. Known or suspected major congenital anomaly that is likely to affect respiratory status (e.g. upper airway obstruction, congenital lung malformation, major congenital heart disease); or severe pulmonary hypoplasia following premature prolonged rupture of fetal membranes with resultant severe oligo/anhydramnios, where the clinician, based on clinical assessment on the first postnatal day, feels survival is unlikely 4. Infant likely to be transferred to another non-participating NICU within 24 hours of birth Additional exclusion criteria for PLUSS-HEARTS include (any of the following): 1. Treatment with prophylactic indomethacin (with the objective of reducing the risk of intraventricular haemorrhage) 2. Major congenital heart disease detected on cardiac ultrasound 3. Unable to perform study cardiac ultrasound due to clinical instability or redirection of care towards comfort measures.
Outcome results
None listed