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

a Multicentre, Double-blind, Randomized, Placebo-controlled Phase III Trial of the Inhaled β2-adrenergic Receptor Agonist Salbutamol for Transient Tachypnoea of the Newborn (the REFSAL Trial)

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05527704

Acronym

REFSAL

Enrollment

608

Registered

2022-09-02

Start date

2021-12-31

Completion date

2026-09-30

Last updated

2025-11-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

TTN, Respiratory Failure, PPHN

Keywords

TTN, PPHN, CPAP, Salbutamol

Brief summary

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).

Detailed 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.

Interventions

DRUGSalbutamol

Patients assigned to the active group will be treated with 0.15 mg/kg body weight (diluted in 3 mL 0.9% NaCl) nebulized salbutamol (Ventolin®, GlaxoSmithKline, Dublin, Ireland) for 30 min.

DRUG0,9% Chloride Sodium

3 mL nebulized 0.9% NaCl administered for 30 min.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

No minimum to 24 Hours

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)

Design outcomes

Primary

Measure	Time frame	Description
Persistent Pulmonary Hypertension of the Newborn (PPHN)	7 days of life	PPHN defined as the need for ventilation with FiO2 \>0.30 and features of increased pulmonary pressure on echocardiogram

Secondary

Measure	Time frame	Description
need for intubation	7 days of life	frequency of need for intubation
duration of ventilation	7 days of life	duration of ventilation e.g. non-invasive ventilation
duration of hospitalization	up to first month of life	duration of hospitalisation after birth
the severity of respiratory distress	48 hrs of life	assessed with the modified TTN Silverman score

Countries

Poland

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 10, 2026