TTNPhase 3REFSALNCT05527704
the Inhaled β2-adrenergic Receptor Agonist for Transient Tachypnoea of the Newborn (the REFSAL Trial)
A Phase 3 study testing Salbutamol and 0,9% Chloride Sodium in people with TTN and Respiratory Failure, run by Medical University of Warsaw at 1 site in Poland.
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). Read more about this study
- Who is it for?
- Ages Up to 24 hours
- Conditions the study is for
- TTN, Respiratory Failure, PPHN
- What is being tested?
- Salbutamol and 0,9% Chloride Sodium
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 608 participants
- Where
- 1 sitePoland
- Study dates
- 31 Dec 2021to 30 Sep 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 24 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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 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).
Read the 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
- Being tested
- Salbutamol, 0,9% Chloride Sodium
- Keywords
- TTN, PPHN, CPAP, Salbutamol
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalbutamolDrug
Also called Albuterol
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 SodiumDrug
Also called 0,9% NaCl
3 mL nebulized 0.9% NaCl administered for 30 min.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: 0,9% Chloride Sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 7 days of life
Secondary outcomes (4)
the severity of respiratory distress
assessed with the modified TTN Silverman score
Measured: 48 hrs of life
need for intubation
frequency of need for intubation
Measured: 7 days of life
duration of ventilation
duration of ventilation e.g. non-invasive ventilation
Measured: 7 days of life
duration of hospitalization
duration of hospitalisation after birth
Measured: up to first month of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2022
- Study start31 Dec 2021
- Primary completion30 Nov 2025 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TTNStudies of the same condition, open and under way.
- More trials run by Medical University of WarsawThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 608 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Warsaw
- Sponsor type
- University, hospital or other
- 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, SZPITAL SPECJALISTYCZNY IM. ŚW. RODZINY w Warszawie, Neonatology Unit, Szpital Specjalistyczny Pro-Familia, Rzeszow
- Responsible party
- Sponsor
- Investigators
- Renata Bokiniec, MD, PhD, Principal investigator, Medical University of Warsaw
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05527704
- Sponsor's protocol ID
- 2019/ABM/01/00058/P/03
- Other IDs
- 2020-003913-36
- Acronym
- REFSAL
- Status last verified
- Sep 2025
- First submitted
- 31 Aug 2022
- Last updated
- 18 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 36714639
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05527704
- Acronym / sponsor ID
- REFSAL / 2019/ABM/01/00058/P/03
- Conditions
- TTN, Respiratory Failure, PPHN
- Keywords
- TTN, PPHN, CPAP, Salbutamol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 608 participants (estimated)
- Lead sponsor
- Medical University of WarsawUniversity, hospital or other
- 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, SZPITAL SPECJALISTYCZNY IM. ŚW. RODZINY w Warszawie, Neonatology Unit, Szpital Specjalistyczny Pro-Familia, Rzeszow
- Study start
- 31 Dec 2021 (actual)
- Primary completion
- 30 Nov 2025 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 2 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CPAP+Salbutamol | Active comparator | Drug: SalbutamolAll 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. |
| CPAP+Placebo | Placebo comparator | Drug: 0,9% Chloride SodiumPatients 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 |
Who may qualify
- Ages
- Up to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SalbutamolAlso: AlbuterolPatients 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. | Drug | CPAP+Salbutamol |
| 0,9% Chloride SodiumAlso: 0,9% NaCl3 mL nebulized 0.9% NaCl administered for 30 min. | Drug | CPAP+Placebo |
Primary outcome
Persistent Pulmonary Hypertension of the Newborn (PPHN)
Time frame: 7 days of life
PPHN defined as the need for ventilation with FiO2 >0.30 and features of increased pulmonary pressure on echocardiogram
4 secondary outcomes
the severity of respiratory distress
Time frame: 48 hrs of life
need for intubation
Time frame: 7 days of life
duration of ventilation
Time frame: 7 days of life
duration of hospitalization
Time frame: up to first month of life
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2025.
- Derived from this study: PubMed 36714639Madajczak 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Renata Bokiniec, MD, PhD principal investigator
Medical University of Warsaw
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Salbutamol and 0,9% Chloride Sodium in people with TTN and Respiratory Failure, run by Medical University of Warsaw at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Persistent Pulmonary Hypertension of the Newborn (PPHN) (time frame: 7 days of life). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05527704, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.