search
Back to results

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

Primary Purpose

TTN, Respiratory Failure, PPHN

Status
Recruiting
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
salbutamol
0,9% Chloride Sodium
Sponsored by
Medical University of Warsaw
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for TTN focused on measuring TTN, PPHN, CPAP, Salbutamol

Eligibility Criteria

undefined - 24 Hours (Child)All SexesDoes not accept 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)

Sites / Locations

  • Medical University of WarsawRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

CPAP+Salbutamol

CPAP+Placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

the severity of respiratory distress
assessed with the modified TTN Silverman score
need for intubation
frequency of need for intubation
duration of ventilation
duration of ventilation e.g. non-invasive ventilation
duration of hospitalization
duration of hospitalisation after birth

Full Information

First Posted
August 31, 2022
Last Updated
September 11, 2023
Sponsor
Medical University of Warsaw
Collaborators
University of Ottawa, Jagiellonian University, Pomeranian Medical University Szczecin, Poznan University of Medical Sciences, Jan Biziel University Hospital No 2 in Bydgoszcz, Neonatology Unit, Specialist Hospital No 2, Bytom, University of Rzeszow, University in Zielona Góra
search

1. Study Identification

Unique Protocol Identification Number
NCT05527704
Brief Title
the Inhaled β2-adrenergic Receptor Agonist for Transient Tachypnoea of the Newborn (the REFSAL Trial)
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 31, 2021 (Actual)
Primary Completion Date
November 30, 2025 (Anticipated)
Study Completion Date
September 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of Warsaw
Collaborators
University of Ottawa, Jagiellonian University, Pomeranian Medical University Szczecin, Poznan University of Medical Sciences, Jan Biziel University Hospital No 2 in Bydgoszcz, Neonatology Unit, Specialist Hospital No 2, Bytom, University of Rzeszow, University in Zielona Góra

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
TTN, Respiratory Failure, PPHN
Keywords
TTN, PPHN, CPAP, Salbutamol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
608 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CPAP+Salbutamol
Arm Type
Active Comparator
Arm Description
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.
Arm Title
CPAP+Placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
salbutamol
Intervention Description
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
Intervention Name(s)
0,9% Chloride Sodium
Other Intervention Name(s)
0,9% NaCl
Intervention Description
3 mL nebulized 0.9% NaCl administered for 30 min.
Primary Outcome Measure Information:
Title
Persistent Pulmonary Hypertension of the Newborn (PPHN)
Description
PPHN defined as the need for ventilation with FiO2 >0.30 and features of increased pulmonary pressure on echocardiogram
Time Frame
7 days of life
Secondary Outcome Measure Information:
Title
the severity of respiratory distress
Description
assessed with the modified TTN Silverman score
Time Frame
48 hrs of life
Title
need for intubation
Description
frequency of need for intubation
Time Frame
7 days of life
Title
duration of ventilation
Description
duration of ventilation e.g. non-invasive ventilation
Time Frame
7 days of life
Title
duration of hospitalization
Description
duration of hospitalisation after birth
Time Frame
up to first month of life

10. Eligibility

Sex
All
Maximum Age & Unit of Time
24 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Facility Information:
Facility Name
Medical University of Warsaw
City
Warsaw
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Renata Bokiniec, Assoc
Phone
+48225966155
Email
renata.bokiniec@wum.edu.pl
First Name & Middle Initial & Last Name & Degree
Dariusz P. Madajczak, PhD
Phone
+48225966267
Email
dariusz.madajczak@wum.edu.pl

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs