the Inhaled β2-adrenergic Receptor Agonist for Transient Tachypnoea of the Newborn (the REFSAL Trial)

Medical University of Warsaw

Status and phase: Enrolling; Phase 3

Conditions: Respiratory Failure; TTN; PPHN

Treatments: Drug: 0,9% Chloride Sodium; Drug: Salbutamol

Study type: Interventional

Funder types: Other

Identifiers

NCT05527704

2019/ABM/01/00058/P/03

2020-003913-36 (EudraCT Number)

Details and patient eligibility

About

Clinical trial evaluating the efficacy and safety of salbutamol for the treatment of neonates with a gestational age between 32 and 42 weeks with transient tachypnoea of the newborn (TTN).

Full description

Multicentre, double-blind, phase III trial will include infants with a gestational age between 32 and 42 weeks and respiratory disorders treated in neonatal intensive care units in Poland. Infants will be enrolled no later than 24 h after birth and will be randomly assigned (1:1) to receive nebulized salbutamol with nCPAP or placebo (nebulized 0.9% NaCl) with nCPAP. The primary outcome is the percentage of infants with TTN who develop PPHN.

Enrollment: 608 estimated patients

Sex: All

Ages: Under 24 hours old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Gestational age at birth between 32 and 42 weeks.
2. Respiratory disorders (tachypnea and expiratory grunting) lasting longer than 15 minutes after birth, or present for at least 15 minutes in the first six hrs of life, or a need for non-invasive respiratory support between birth and six hrs of life.
3. Available chest radiographs obtained within six hrs after birth.
4. Available parameters of the acid-base balance (blood pH, partial pressure of O2 and CO2, base excess) and blood serum ionogram for Na+, K+, Ca2+ evaluated in the umbilical cord blood sample.

Exclusion criteria

1. Need for intubation directly after birth or perinatal asphyxia, defined as abnormal acid-base parameters detected in an umbilical cord blood sample (pH <7.0 or base excess < -14 mmol/L).
2. Multiple apnea-brady that require immediate intubation before a trial of NIV
3. Age >24 h.
4. Meconium aspiration syndrome.
5. Air leak syndrome.
6. Congenital heart disease.
7. Congenital diaphragmatic hernia.
8. Other severe congenital malformations and genetic disorders (diagnosed before and after birth) associated with increased risk of respiratory failure.
9. The need for a surfactant administration immediately after birth, regardless of the method of its administration (respiratory distress syndrome - RDS)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

608 participants in 2 patient groups, including a placebo group

CPAP+Salbutamol

Active Comparator group

Description:

All patients will receive nCPAP at 5-6 cm H2O pressure with an oxygen concentration of 21% or more to maintain preductal saturation between 90% and 95%. Patients assigned to the active group will be treated with 0.15 mg/kg body weight (diluted in 3 mL 0.9% NaCl) nebulised salbutamol (Ventolin®, GlaxoSmithKline, Dublin, Ireland) for 30 min.

Treatment:

Drug: Salbutamol

CPAP+Placebo

Placebo Comparator group

Description:

Patients in the placebo group will also receive nCPAP at 5-6 cm H2O pressure with an oxygen concentration of 21% or more to maintain preductal saturation between 90% and 95%. In addition, patients will receive 3 mL nebulised 0.9% NaCl administered for 30 min. as a placebo

Treatment:

Drug: 0,9% Chloride Sodium