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

NCT ID: NCT05527704

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 608 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-31
• Study Completion Date: 2026-09-30

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.

Conditions

TTN; Respiratory Failure; PPHN

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CPAP+Salbutamol

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.

Group Type: ACTIVE_COMPARATOR

Salbutamol

Intervention Type: DRUG

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.

CPAP+Placebo

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

Group Type: PLACEBO_COMPARATOR

0,9% Chloride Sodium

Intervention Type: DRUG

3 mL nebulized 0.9% NaCl administered for 30 min.

Interventions

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.

Intervention Type: DRUG

0,9% Chloride Sodium

3 mL nebulized 0.9% NaCl administered for 30 min.

Intervention Type: DRUG

Other Intervention Names

Albuterol; 0,9% NaCl

Eligibility Criteria

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)

• Maximum Eligible Age: 24 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Ottawa

OTHER

Sponsor Role: collaborator

Jagiellonian University

OTHER

Sponsor Role: collaborator

Pomeranian Medical University Szczecin

OTHER

Sponsor Role: collaborator

Poznan University of Medical Sciences

OTHER

Sponsor Role: collaborator

Jan Biziel University Hospital No 2 in Bydgoszcz

OTHER

Sponsor Role: collaborator

Neonatology Unit, Specialist Hospital No 2, Bytom

UNKNOWN

Sponsor Role: collaborator

University of Rzeszow

OTHER

Sponsor Role: collaborator

University in Zielona Góra

OTHER

Sponsor Role: collaborator

SZPITAL SPECJALISTYCZNY IM. ŚW. RODZINY w Warszawie

UNKNOWN

Sponsor Role: collaborator

Neonatology Unit, Szpital Specjalistyczny Pro-Familia, Rzeszow

UNKNOWN

Sponsor Role: collaborator

Medical University of Warsaw

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Renata Bokiniec, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Warsaw

Locations

Medical University of Warsaw

Warsaw, , Poland

Countries

Poland

References

Madajczak D, Daboval T, Lauterbach R, Loniewska B, Blaz W, Szczapa T, Sadowska-Krawczenko I, Michalak-Kloc M, Slawska H, Borszewska-Kornacka M, Bokiniec R; REFSAL Study Group. Protocol for a multicenter, double-blind, randomized, placebo-controlled phase III trial of the inhaled beta2-adrenergic receptor agonist salbutamol for transient tachypnea of the newborn (the REFSAL trial). Front Pediatr. 2023 Jan 12;10:1060843. doi: 10.3389/fped.2022.1060843. eCollection 2022.

Reference Type: DERIVED

PMID: 36714639 (View on PubMed)

Other Identifiers

2020-003913-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2019/ABM/01/00058/P/03

Identifier Type: -

Identifier Source: org_study_id