Transient Tachypnea of the NewbornPRE-HIFREQNCT03499418
Evaluation of the Prevalence of Persistent Pulmonary Hypertension in Neonates
An observational study of Transient Tachypnea of the Newborn and PPHN, run by Princess Anna Mazowiecka Hospital, Warsaw, Poland at 1 site in Poland.
Trial summary
Transient Tachypnea of the Newborn (TTN) is one of the common causes of neonatal respiratory distress as a result of delayed clearance of fetal lung fluid. Neonates with TTN usually require noninvasive respiratory support (e.g. Read more about this study
- Who is it for?
- Ages 10 minutes to 6 hours
- Conditions the study is for
- Transient Tachypnea of the Newborn, PPHN
- What is being tested?
- modified Silverman scale and echocardiography
- How many people
- 0 participants
- Where
- 1 sitePoland
- Study dates
- 1 Oct 2020to 30 Sep 2024
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
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 10 minutes to 6 hours
- All sexes
- No healthy volunteers
- Child
Study population: The study is a multicenter, prospective, cohort, observational to assess the clinical benefits of using a scale in a population of neonates from 32 to 41 completed weeks PMA who will be admitted to a neonatal intensive care unit (NICU). Before study enrollment, parents (legal guardians) will provide a signed written informed consent form (ICF). ICF form may be signed after subject met inclusion criteria for the study.
Who may be able to join
- A signed form of informed consent from parents (legal guardians).
- 32 0/7 to 41 6/7 weeks of gestation
- The need to support postnatal breathing, no later than 6 hours of life.
Who cannot join
- The need for intubation in the after-birth procedures
- Age above 6 hours of age from birth
- Congenital heart defects
- Congenital diaphragmatic hernia
- Other severe congenital malformations and genetically determined syndromes, diagnosed before and after birth, associated with higher risk of respiratory failure.
Trial locations and contacts
1 site in 1 country.
Poland1 site
Department of Neonatology and Neonatal Intensive Care Medical University of Warsaw
Warsaw, 00-315
About this study
Official title: Evaluation of the Prevalence of Persistent Pulmonary Hypertension in Term and Near-term Neonates - Observational Study
Transient Tachypnea of the Newborn (TTN) is one of the common causes of neonatal respiratory distress as a result of delayed clearance of fetal lung fluid.
Neonates with TTN usually require noninvasive respiratory support (e.g. nasal cannula, nasal CPAP) and may need supplemental oxygen therapy to maintain normal oxygen saturation levels. There have also been reports of "malignant TTN," in which affected children develop persistent pulmonary hypertension of the newborn (PPHN).
Read the detailed description
Respiratory failure after birth is still a severe problem. Risk factors include premature labor and delivery by cesarean section. Despite the improvement of the quality of perinatal care in Poland, almost a constant percentage of premature babies has been born in Poland. The number of births by cesarean section is also rising - both planned and preceded by the attempt to vaginal delivery. TTN - Transient Tachypnea of the Newborn is one of the most common causes of respiratory failure in newborns. TTN occurs in approximately 10% of newborns born between 33 and 34 weeks of gestation, in about 5% of newborns born between 35 and 36 weeks and less than 1% of neonates.
At baseline of transient tachypnea of the newborn (TTN), there are disorders of absorption of pulmonary fluid. In the flow of water, epithelial sodium channels and Na+ / K+ -ATPase play an essential role. Their stimulation increases the absorption of water from the lung airspace and increases its transport both inside and outside the cell. In the subsequent stages of removal of interstitial pulmonary fluid, the vascular system and the lymphatic system are involved.
TTN is usually a self-limiting process, and treatments are not defined. There are also reports of "malignant TTN" in which infants develop persistent pulmonary hypertension of newborns (PPHN) (3). TTN infants typically require non-invasive respiratory support (CPAP, for example) and may need higher oxygen concentrations in the respiratory mixture to maintain proper oxygenation. Some experts suggest that the early use of expanding pressure (nasal CPAP) may relieve severe forms of TTN and prevent using of mechanical ventilation, and also may eventually prevent the development of persistent pulmonary hypertension.
Persistent pulmonary hypertension of newborns (PPHN) is a disorder arising at the stage of a physiological passage of fetal circulation into the neonatal circulation in the perinatal period. It is associated with a lack of decreasing pulmonary vascular resistance, which is influenced by increasing levels of oxygen in the blood and numerous biochemical and hormonal factors. From own observations and data from the literature, it is estimated that PPHN occurs in approximately 0.1-0.2% of newborns born term or near the term. Treatment of persistent pulmonary hypertension is difficult. Despite the use of mechanical ventilation, inhaled nitric oxide (iNO) or extracorporeal oxygenation (ECMO), the risk of death is still around 10-15%. This percentage has declined in recent years, but it is believed that persistent pulmonary hypertension of newborns is one of the most challenging situations in intensive care of newborns. In addition, infants who have undergone PPHN are exposed to long-term effects in the form of neurological complications or neurodevelopmental disorders.
Before initiating a clinical trial (intervention) with the experimental therapy, an initial follow-up study was conducted to assess the incidence of failure in respiratory insufficiency and the rate of PPHN in neonates born between 32 and 41 weeks of gestation. The failure of treatment will be defined as the need for invasive ventilation (intubation and mechanical ventilation). To accurately determine the degree of respiratory failure, a scale was developed that was an adaptation of the Silverman scale. PPHN will be defined by parameters measured in echocardiography and on changes in blood gases. Also, a comparison of parameters of acid-base balance and the type of treatment of respiratory failure after birth will be performed in the follow-up study. Based on the collected data, validation of the modified Silverman scale and evaluation of its clinical utility will be presented.
- Conditions
- Transient Tachypnea of the Newborn, PPHN
- Being tested
- modified Silverman scale, echocardiography
- Keywords
- newborn, TTN, PPHN
- Medical subject headings
- Transient Tachypnea of the Newborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
modified Silverman scaleOther
Clinical assessment of severity of respiratory failure
echocardiographyDiagnostic test
echocardiographic evaluation of haemodynamic problems
| Study group | Role | What they receive |
|---|---|---|
| newborns with TTN | Group of late preterm and full-term newborns with TTN evaluated by modified Silverman scale Receives: Other: modified Silverman scale | |
| newborns with PPHN | Group of late preterm and full-term newborns with respiratory failure with PPHN evaluated by echocardiography Receives: Other: modified Silverman scale; Diagnostic Test: echocardiography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of PPHN
The primary endpoint for this study is time of respiratory failure (need to intubation) and incidence rate of PPHN
Measured: 12 months
Secondary outcomes (1)
The evaluation of the "TTN scale"
The evaluation of the "TTN scale" in comparison to physiologic parameters:
- Fraction of inspired oxygen (FiO2)
- pH
- Partial pressure of carbon dioxide (pCO2)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2018
- Study start1 Oct 2020 (estimated)
- Primary completion31 Mar 2023 (estimated)
- Study completion30 Sep 2024 (estimated)
Why it stopped: Due to changing methodology of the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Transient Tachypnea of the NewbornStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- Princess Anna Mazowiecka Hospital, Warsaw, Poland
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Renata Bokiniec, Princess Anna Mazowiecka Hospital, Warsaw, Poland
- Investigators
- Maria K. Borszewska-Kornacka, MD, ProfTit, Study chair, Medical University of Warsaw
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03499418
- Sponsor's protocol ID
- PRE-HIFREQ
- Acronym
- PRE-HIFREQ
- Status last verified
- Sep 2022
- First submitted
- 19 Oct 2017
- Last updated
- 4 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Raju TN, Higgins RD, Stark AR, Leveno KJ. Optimizing care and outcome for late-preterm (near-term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics. 2006 Sep;118(3):1207-14. doi: 10.1542/peds.2006-0018.
PubMed 16951017Rubaltelli FF, Dani C, Reali MF, Bertini G, Wiechmann L, Tangucci M, Spagnolo A. Acute neonatal respiratory distress in Italy: a one-year prospective study. Italian Group of Neonatal Pneumology. Acta Paediatr. 1998 Dec;87(12):1261-8. doi: 10.1080/080352598750030951.
PubMed 9894827Lakshminrusimha S, Keszler M. Persistent Pulmonary Hypertension of the Newborn. Neoreviews. 2015 Dec;16(12):e680-e692. doi: 10.1542/neo.16-12-e680.
PubMed 26783388Buchiboyina A, Jasani B, Deshmukh M, Patole S. Strategies for managing transient tachypnoea of the newborn - a systematic review. J Matern Fetal Neonatal Med. 2017 Jul;30(13):1524-1532. doi: 10.1080/14767058.2016.1193143. Epub 2016 Oct 20.
PubMed 27762156
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Prevalence of Persistent Pulmonary Hypertension in Term and Near-term Neonates - Observational Study
- ClinicalTrials.gov ID
- NCT03499418
- Acronym / sponsor ID
- PRE-HIFREQ / PRE-HIFREQ
- Conditions
- Transient Tachypnea of the Newborn, PPHN
- Keywords
- newborn, TTN, PPHN
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Due to changing methodology of the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Princess Anna Mazowiecka Hospital, Warsaw, PolandUniversity, hospital or other
- Study start
- 1 Oct 2020 (estimated)
- Primary completion
- 31 Mar 2023 (estimated)
- Study completion
- 30 Sep 2024 (estimated)
- First posted
- 17 Apr 2018 (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.
Transient Tachypnea of the Newborn (TTN) is one of the common causes of neonatal respiratory distress as a result of delayed clearance of fetal lung fluid.
Neonates with TTN usually require noninvasive respiratory support (e.g. nasal cannula, nasal CPAP) and may need supplemental oxygen therapy to maintain normal oxygen saturation levels. There have also been reports of "malignant TTN," in which affected children develop persistent pulmonary hypertension of the newborn (PPHN).
Detailed description
Respiratory failure after birth is still a severe problem. Risk factors include premature labor and delivery by cesarean section. Despite the improvement of the quality of perinatal care in Poland, almost a constant percentage of premature babies has been born in Poland. The number of births by cesarean section is also rising - both planned and preceded by the attempt to vaginal delivery. TTN - Transient Tachypnea of the Newborn is one of the most common causes of respiratory failure in newborns. TTN occurs in approximately 10% of newborns born between 33 and 34 weeks of gestation, in about 5% of newborns born between 35 and 36 weeks and less than 1% of neonates.
At baseline of transient tachypnea of the newborn (TTN), there are disorders of absorption of pulmonary fluid. In the flow of water, epithelial sodium channels and Na+ / K+ -ATPase play an essential role. Their stimulation increases the absorption of water from the lung airspace and increases its transport both inside and outside the cell. In the subsequent stages of removal of interstitial pulmonary fluid, the vascular system and the lymphatic system are involved.
TTN is usually a self-limiting process, and treatments are not defined. There are also reports of "malignant TTN" in which infants develop persistent pulmonary hypertension of newborns (PPHN) (3). TTN infants typically require non-invasive respiratory support (CPAP, for example) and may need higher oxygen concentrations in the respiratory mixture to maintain proper oxygenation. Some experts suggest that the early use of expanding pressure (nasal CPAP) may relieve severe forms of TTN and prevent using of mechanical ventilation, and also may eventually prevent the development of persistent pulmonary hypertension.
Persistent pulmonary hypertension of newborns (PPHN) is a disorder arising at the stage of a physiological passage of fetal circulation into the neonatal circulation in the perinatal period. It is associated with a lack of decreasing pulmonary vascular resistance, which is influenced by increasing levels of oxygen in the blood and numerous biochemical and hormonal factors. From own observations and data from the literature, it is estimated that PPHN occurs in approximately 0.1-0.2% of newborns born term or near the term. Treatment of persistent pulmonary hypertension is difficult. Despite the use of mechanical ventilation, inhaled nitric oxide (iNO) or extracorporeal oxygenation (ECMO), the risk of death is still around 10-15%. This percentage has declined in recent years, but it is believed that persistent pulmonary hypertension of newborns is one of the most challenging situations in intensive care of newborns. In addition, infants who have undergone PPHN are exposed to long-term effects in the form of neurological complications or neurodevelopmental disorders.
Before initiating a clinical trial (intervention) with the experimental therapy, an initial follow-up study was conducted to assess the incidence of failure in respiratory insufficiency and the rate of PPHN in neonates born between 32 and 41 weeks of gestation. The failure of treatment will be defined as the need for invasive ventilation (intubation and mechanical ventilation). To accurately determine the degree of respiratory failure, a scale was developed that was an adaptation of the Silverman scale. PPHN will be defined by parameters measured in echocardiography and on changes in blood gases. Also, a comparison of parameters of acid-base balance and the type of treatment of respiratory failure after birth will be performed in the follow-up study. Based on the collected data, validation of the modified Silverman scale and evaluation of its clinical utility will be presented.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| newborns with TTN | – | Other: modified Silverman scaleGroup of late preterm and full-term newborns with TTN evaluated by modified Silverman scale |
| newborns with PPHN | – | Other: modified Silverman scale, Diagnostic Test: echocardiographyGroup of late preterm and full-term newborns with respiratory failure with PPHN evaluated by echocardiography |
Who may qualify
- Ages
- 10 minutes to 6 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The study is a multicenter, prospective, cohort, observational to assess the clinical benefits of using a scale in a population of neonates from 32 to 41 completed weeks PMA who will be admitted to a neonatal intensive care unit (NICU). Before study enrollment, parents (legal guardians) will provide a signed written informed consent form (ICF). ICF form may be signed after subject met inclusion criteria for the study.
Key inclusion criteria (3 listed)
- A signed form of informed consent from parents (legal guardians).
- 32 0/7 to 41 6/7 weeks of gestation
- The need to support postnatal breathing, no later than 6 hours of life.
Key exclusion criteria (5 listed)
- The need for intubation in the after-birth procedures
- Age above 6 hours of age from birth
- Congenital heart defects
- Congenital diaphragmatic hernia
- Other severe congenital malformations and genetically determined syndromes, diagnosed before and after birth, associated with higher risk of respiratory failure.
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 |
|---|---|---|
| modified Silverman scaleClinical assessment of severity of respiratory failure | Other | newborns with PPHN, newborns with TTN |
| echocardiographyechocardiographic evaluation of haemodynamic problems | Diagnostic test | newborns with PPHN |
Primary outcome
Rate of PPHN
Time frame: 12 months
The primary endpoint for this study is time of respiratory failure (need to intubation) and incidence rate of PPHN
1 secondary outcome
The evaluation of the "TTN scale"
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2022.
- Background: PubMed 16951017Raju TN, Higgins RD, Stark AR, Leveno KJ. Optimizing care and outcome for late-preterm (near-term) infants: a summary of the workshop sponsored by the National Institute of Child Health and Human Development. Pediatrics. 2006 Sep;118(3):1207-14. doi: 10.1542/peds.2006-0018.
- Background: PubMed 9894827Rubaltelli FF, Dani C, Reali MF, Bertini G, Wiechmann L, Tangucci M, Spagnolo A. Acute neonatal respiratory distress in Italy: a one-year prospective study. Italian Group of Neonatal Pneumology. Acta Paediatr. 1998 Dec;87(12):1261-8. doi: 10.1080/080352598750030951.
- Background: PubMed 26783388Lakshminrusimha S, Keszler M. Persistent Pulmonary Hypertension of the Newborn. Neoreviews. 2015 Dec;16(12):e680-e692. doi: 10.1542/neo.16-12-e680.
- Background: PubMed 27762156Buchiboyina A, Jasani B, Deshmukh M, Patole S. Strategies for managing transient tachypnoea of the newborn - a systematic review. J Matern Fetal Neonatal Med. 2017 Jul;30(13):1524-1532. doi: 10.1080/14767058.2016.1193143. Epub 2016 Oct 20.
- Individual participant dataSharing planned: Undecided
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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.
Maria K. Borszewska-Kornacka, MD, ProfTit study chair
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?
An observational study of Transient Tachypnea of the Newborn and PPHN, run by Princess Anna Mazowiecka Hospital, Warsaw, Poland 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 3 inclusion and 5 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: withdrawn, as of the sponsor's last update on 4 Oct 2022. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Rate of PPHN (time frame: 12 months). 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 NCT03499418, which also lists 4 linked publications.
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 4 Oct 2022; AzTrials last refreshed its copy on 8 Nov 2026.