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

Respiratory Failure Clinical Trial

— REFSAL  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05527704
• Other study ID #: 2019/ABM/01/00058/P/03
• Secondary ID: 2020-003913-36
• Status: Recruiting
• Phase: Phase 3
• Start date: December 31, 2021
• Est. completion date: September 30, 2026

Study information

• Verified date: September 2023
• Source: Medical University of Warsaw
• Contact: Renata Bokiniec, MD, PhD, Assoc Prof
• Phone: +48225966155
• Email: renata.bokiniec[@]wum.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 608
• Est. completion date: September 30, 2026
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

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)

Related Conditions & MeSH terms

• PPHN
• Respiratory Failure
• Respiratory Insufficiency
• Tachypnea
• Transient Tachypnea of the Newborn
• TTN

Intervention

Drug:
• Salbutamol
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.
• 0,9% Chloride Sodium
3 mL nebulized 0.9% NaCl administered for 30 min.

Locations

Country	Name	City	State
Poland	Medical University of Warsaw	Warsaw

Sponsors (9)

Lead Sponsor	Collaborator
Medical University of Warsaw	Jagiellonian University, Jan Biziel University Hospital No 2 in Bydgoszcz, Neonatology Unit, Specialist Hospital No 2, Bytom, Pomeranian Medical University Szczecin, Poznan University of Medical Sciences, University in Zielona Góra, University of Ottawa, University of Rzeszow

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Persistent Pulmonary Hypertension of the Newborn (PPHN)	PPHN defined as the need for ventilation with FiO2 >0.30 and features of increased pulmonary pressure on echocardiogram	7 days of life
Secondary	the severity of respiratory distress	assessed with the modified TTN Silverman score	48 hrs of life
Secondary	need for intubation	frequency of need for intubation	7 days of life
Secondary	duration of ventilation	duration of ventilation e.g. non-invasive ventilation	7 days of life
Secondary	duration of hospitalization	duration of hospitalisation after birth	up to first month of life