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

NCT05527704 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: 2019/ABM/01/00058/P/032020-003913-36
• Study Type: interventional
• Target: 608
• Locations: 1 country
• Sites: 1

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).

Conditions

TTN; Respiratory Failure; PPHN

Keywords

TTN; PPHN; CPAP; Salbutamol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• the severity of respiratory distress

  48 hrs of life

• need for intubation

  7 days of life

• duration of ventilation

  7 days of life

• duration of hospitalization

  up to first month of life

Study Arms (2)

CPAP+Salbutamol

ACTIVE COMPARATOR

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.

Drug: Salbutamol

CPAP+Placebo

PLACEBO COMPARATOR

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

Drug: 0,9% Chloride Sodium

Interventions

Salbutamol 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.

Also known as: Albuterol

CPAP+Salbutamol

0,9% Chloride Sodium DRUG

3 mL nebulized 0.9% NaCl administered for 30 min.

Also known as: 0,9% NaCl

CPAP+Placebo

Eligibility Criteria

• Age: Up to 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gestational age at birth between 32 and 42 weeks.
• 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.
• Available chest radiographs obtained within six hrs after birth.
• 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.

You may not qualify if:

• 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).
• Multiple apnea-brady that require immediate intubation before a trial of NIV
• Age \>24 h.
• Meconium aspiration syndrome.
• Air leak syndrome.
• Congenital heart disease.
• Congenital diaphragmatic hernia.
• Other severe congenital malformations and genetic disorders (diagnosed before and after birth) associated with increased risk of respiratory failure.
• The need for a surfactant administration immediately after birth, regardless of the method of its administration (respiratory distress syndrome - RDS)

Sponsors & Collaborators

• Medical University of Warsaw: lead
• University of Ottawa: collaborator
• Jagiellonian University: collaborator
• Pomeranian Medical University Szczecin: collaborator
• Poznan University of Medical Sciences: collaborator
• Jan Biziel University Hospital No 2 in Bydgoszcz: collaborator
• Neonatology Unit, Specialist Hospital No 2, Bytom: collaborator
• University of Rzeszow: collaborator
• University in Zielona Góra: collaborator
• SZPITAL SPECJALISTYCZNY IM. ŚW. RODZINY w Warszawie: collaborator
• Neonatology Unit, Szpital Specjalistyczny Pro-Familia, Rzeszow: collaborator

Study Sites (1)

Medical University of Warsaw

Warsaw, Poland

Location

Related Publications (1)

• 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.

  PMID: 36714639 DERIVED

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Albuterol

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Officials

• Renata Bokiniec, MD, PhD

  Medical University of Warsaw

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2022
• First Posted: September 2, 2022
• Study Start: December 31, 2021
• Primary Completion: November 30, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: November 18, 2025

Record last verified: 2025-09

Locations

PL (1)