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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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TTN, Respiratory Failure, PPHN

Intervention / Treatment
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* Drug: salbutamol
* Drug: 0,9% Chloride Sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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)

Ages Eligible for Study
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Maximum Age: 24 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CPAP+Salbutamol<br>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<br>* 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.<br>|
| Placebo Comparator: CPAP+Placebo<br>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<br>* 3 mL nebulized 0.9% NaCl administered for 30 min.<br>* Other names: 0,9% NaCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TTN, PPHN, CPAP, Salbutamol