Pulmonary HypertensionNCT04402645
Novel Echocardiographic Methods for Early Identification of Neonates at Risk for Chronic Pulmonary Hypertension
An observational study of Pulmonary Hypertension and Infant, Premature, run by Mount Sinai Hospital, Canada at 6 sites in 4 countries.
Trial summary
Chronic pulmonary hypertension (cPHT) is a serious cardiopulmonary disorder that causes low oxygen levels in the blood, difficulty in breathing and ultimately heart failure. Newborn babies born extremely premature frequently suffer from cPHT while receiving treatment in neonatal intensive care units and are more… Read more about this study
- Who is it for?
- Ages 14 days and older
- Conditions the study is for
- Pulmonary Hypertension, Infant, Premature
- How many people
- 350 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 31 Aug 2017to 1 Apr 2024
- 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 14 days and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Preterm infants will be recruited from tertiary neonatal intensive care units (NICUs) in Toronto (Mount Sinai Hospital and Sunnybrook Health Sciences Centre) and Vancouver (BC Women's Hospital \& Health Centre) Canada, the United States (University of Iowa Health Care, Iowa), and Europe (Liverpool University Hospitals NHS Foundation Trust and The Rotunda Hospital)
Who may be able to join
- Gestational age at birth ≤26+6/7 and/or birth weight <1000g
- Alive at two weeks of postnatal age
- Infant cleared by the clinical team for approach
Who cannot join
- Known major congenital and/or genetic anomaly
- Congenital heart defects (CHD) except patent ductus arteriosus (PDA), patent foramen ovale (PFO), peripheral pulmonary artery stenosis and small (< 3 mm in diameter) ventricular septal defects
- Any condition which, in the opinion of the investigator, would preclude enrollment
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
Canada3 sites
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
BC Women's Hospital & Health Centre
Vancouver, British Columbia, V6H 3N1
United States1 site
University of Iowa Health Care
Iowa City, Iowa, 52242
About this study
Official title: Early Identification of Preterm Neonates With Evolving Chronic Pulmonary Hypertension: Utility of Functional Echocardiographic Markers
Chronic pulmonary hypertension (cPHT) is a serious cardiopulmonary disorder that causes low oxygen levels in the blood, difficulty in breathing and ultimately heart failure. Newborn babies born extremely premature frequently suffer from cPHT while receiving treatment in neonatal intensive care units and are more likely to die than those without cPHT. Echocardiography is the investigation of choice for the assessment of heart function in premature infants however however there is a significant lack of standardization, sensitivity, and reliability for echocardiography parameters and a lack of consensus regarding optimal detection timing. In adults and older children it is known that early diagnosis and treatment, particularly before right side of the heart fails, is an important determinant of treatment success and survival. Diagnosis late in postnatal course for preterm infants remains a major barrier to timely and effective treatment.
The primary objective of this study is to develop new, sensitive, quantitative echocardiographic diagnostic criteria which will allow for the identification of extreme preterm neonates suffering from significantly high pressure in their pulmonary blood vessels, early in postnatal course, when the disease is likely to be most amenable to preventative/curative treatment.
This is an international initiative that will leverage expertise about echocardiography techniques and cardiopulmonary physiology of preterm infants.The results of this study will have an immediate impact on the day-to-day care of these highly vulnerable infants. The results will lead to increased awareness among clinicians, inform future surveillance protocols and diagnostic timing, and provide ideal preparation for future therapeutic trials.
Read the detailed description
This is a multi-centre prospective observational study to develop new quantitative echocardiography diagnostic criteria sensitive to identify the presence of chronic pulmonary hypertension early in postnatal course. The investigators hypothesize that echocardiographic markers of pulmonary vascular resistance (PVR) and right ventricular (RV) function will allow early identification of extremely low birth weight (ELBW) preterm neonates who subsequently develop chronic pulmonary hypertension in association with chronic neonatal lung disease. More specifically, based on previous work and preliminary data, the investigators hypothesize that tricuspid annular plane systolic excursion (TAPSE- a routinely used marker of right heart function) and pulmonary artery acceleration time (PAAT- a routinely used marker of resistance in the pulmonary blood vessels) either alone or in combination will be the most sensitive parameters for early identification reducing the time to diagnosis compared to contemporary clinical practice.
The aim of the study is to recruit a large cohort of extreme premature neonates at two weeks of age and sequentially perform two "early-diagnostic assessments". First assessment will be performed between 14-21 days of life and the second at a corrected gestational age (CGA) of 32 weeks. Assessment will include a focused ultrasound of the heart to measure pre-defined markers which are under investigation. The investigators will test the diagnostic utility of these markers separately for each time point. All babies will also have a standard diagnostic assessment for evaluation of cPHT at 36 weeks CGA, as per routine practice. The study team will record this data for participants, along with their relevant medical details and clinical outcomes, including neurodevelopment assessments performed at 18 months of age as a routine clinical follow-up. At the end of this study, the investigators will divide the cohort into those who developed cPHT and those who did not as per currently used standard criteria and will compare the results of new parameters obtained at earlier time points. The sensitivity of each marker to pick-up early cPHT will be calculated and its correlation with health outcomes will be established.
- Conditions
- Pulmonary Hypertension, Infant, Premature
- Keywords
- Premature Infant, Pulmonary Hypertension, Echocardiography, Extremely Low Birth Weight Neonate, Pulmonary Vascular Resistance, Right Ventricular Function
- Medical subject headings
- Hypertension, Pulmonary, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Chronic pulmonary hypertension | Diagnosis on echocardiography at 36 weeks CGA using standard criteria (flat interventricular septal motion or right ventricular dilatation) | |
| No chronic pulmonary hypertension | Confirmed on echocardiography at 36 weeks CGA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic test characteristics calculated for TAPSE and PAAT against diagnosis of chronic pulmonary hypertension on standard diagnostic assessment
Sensitivity, specificity, positive and negative likelihood ratios for TAPSE and PAAT at each early diagnostic assessment against diagnosis of chronic pulmonary hypertension on standard diagnostic assessment using echocardiography using current standard criteria
Measured: Early diagnostic assessments (14-21 days postnatal age; 32+0/7-32+6/7); Standard diagnostic assessment (~36 weeks CGA)
Secondary outcomes (3)
Composite of Death/ Chronic Neonatal Lung Disease
Infant death prior to 36 weeks CGA and chronic neonatal lung disease are competing risks for the primary outcome of chronic pulmonary hypertension. The presence of both will be assessed.
Measured: Composite outcome measure will be assessed on the date of discharge for each study participant from the study Neonatal Intensive Care Unit (NICU) or date of death during admission (if applicable) up to 365 days.
Duration of need for respiratory support
Total duration of need (number of days) for invasive, non-invasive and supplemental (low-flow) oxygen support
Measured: Outcome measure will be assessed on the date of discharge for each study participant from the study Neonatal Intensive Care Unit (NICU) or date of death during admission (if applicable) up to 365 days.
Length of hospital stay
Length of NICU admission from birth to discharge (number of days)
Measured: Outcome measure will be assessed on the date of discharge for each study participant from the study Neonatal Intensive Care Unit (NICU) or date of death during admission (if applicable) up to 365 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2020
- Study start31 Aug 2017
- Primary completion31 Aug 2022
- Study completion1 Apr 2024
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 Pulmonary HypertensionStudies 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
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre, Liverpool Women's NHS Foundation Trust, The Rotunda Hospital, University of Iowa, BC Women's Hospital & Health Centre
- Responsible party
- Sponsor
- Investigators
- Amish Jain, MD, PHD, Principal investigator, Staff Neonatologist, Clinician Scientist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04402645
- Sponsor's protocol ID
- 16-0111-E
- Status last verified
- Feb 2024
- First submitted
- 13 May 2020
- Last updated
- 14 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Thomas L, Baczynski M, Deshpande P, Kharrat A, Joye S, Zhu F, Ibarra-Rios D, Shah PS, Mertens L, Jankov RP, Ye XY, Neary E, Ting J, Castaldo M, Levy P, Smith A, El-Khuffash AF, Giesinger RE, McNamara PJ, Weisz DE, Jain A. Multicentre prospective observational study exploring the predictive value of functional echocardiographic indices for early identification of preterm neonates at risk of developing chronic pulmonary hypertension secondary to chronic neonatal lung disease. BMJ Open. 2021 Mar 31;11(3):e044924. doi: 10.1136/bmjopen-2020-044924.
PubMed 33789855
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Identification of Preterm Neonates With Evolving Chronic Pulmonary Hypertension: Utility of Functional Echocardiographic Markers
- ClinicalTrials.gov ID
- NCT04402645
- Acronym / sponsor ID
- 16-0111-E
- Conditions
- Pulmonary Hypertension, Infant, Premature
- Keywords
- Premature Infant, Pulmonary Hypertension, Echocardiography, Extremely Low Birth Weight Neonate, Pulmonary Vascular Resistance, Right Ventricular Function
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 350 participants (actual)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Collaborators
- Sunnybrook Health Sciences Centre, Liverpool Women's NHS Foundation Trust, The Rotunda Hospital, University of Iowa, BC Women's Hospital & Health Centre
- Study start
- 31 Aug 2017 (actual)
- Primary completion
- 31 Aug 2022 (actual)
- Study completion
- 1 Apr 2024 (actual)
- First posted
- 27 May 2020 (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.
Chronic pulmonary hypertension (cPHT) is a serious cardiopulmonary disorder that causes low oxygen levels in the blood, difficulty in breathing and ultimately heart failure. Newborn babies born extremely premature frequently suffer from cPHT while receiving treatment in neonatal intensive care units and are more likely to die than those without cPHT. Echocardiography is the investigation of choice for the assessment of heart function in premature infants however however there is a significant lack of standardization, sensitivity, and reliability for echocardiography parameters and a lack of consensus regarding optimal detection timing. In adults and older children it is known that early diagnosis and treatment, particularly before right side of the heart fails, is an important determinant of treatment success and survival. Diagnosis late in postnatal course for preterm infants remains a major barrier to timely and effective treatment.
The primary objective of this study is to develop new, sensitive, quantitative echocardiographic diagnostic criteria which will allow for the identification of extreme preterm neonates suffering from significantly high pressure in their pulmonary blood vessels, early in postnatal course, when the disease is likely to be most amenable to preventative/curative treatment.
This is an international initiative that will leverage expertise about echocardiography techniques and cardiopulmonary physiology of preterm infants.The results of this study will have an immediate impact on the day-to-day care of these highly vulnerable infants. The results will lead to increased awareness among clinicians, inform future surveillance protocols and diagnostic timing, and provide ideal preparation for future therapeutic trials.
Detailed description
This is a multi-centre prospective observational study to develop new quantitative echocardiography diagnostic criteria sensitive to identify the presence of chronic pulmonary hypertension early in postnatal course. The investigators hypothesize that echocardiographic markers of pulmonary vascular resistance (PVR) and right ventricular (RV) function will allow early identification of extremely low birth weight (ELBW) preterm neonates who subsequently develop chronic pulmonary hypertension in association with chronic neonatal lung disease. More specifically, based on previous work and preliminary data, the investigators hypothesize that tricuspid annular plane systolic excursion (TAPSE- a routinely used marker of right heart function) and pulmonary artery acceleration time (PAAT- a routinely used marker of resistance in the pulmonary blood vessels) either alone or in combination will be the most sensitive parameters for early identification reducing the time to diagnosis compared to contemporary clinical practice.
The aim of the study is to recruit a large cohort of extreme premature neonates at two weeks of age and sequentially perform two "early-diagnostic assessments". First assessment will be performed between 14-21 days of life and the second at a corrected gestational age (CGA) of 32 weeks. Assessment will include a focused ultrasound of the heart to measure pre-defined markers which are under investigation. The investigators will test the diagnostic utility of these markers separately for each time point. All babies will also have a standard diagnostic assessment for evaluation of cPHT at 36 weeks CGA, as per routine practice. The study team will record this data for participants, along with their relevant medical details and clinical outcomes, including neurodevelopment assessments performed at 18 months of age as a routine clinical follow-up. At the end of this study, the investigators will divide the cohort into those who developed cPHT and those who did not as per currently used standard criteria and will compare the results of new parameters obtained at earlier time points. The sensitivity of each marker to pick-up early cPHT will be calculated and its correlation with health outcomes will be established.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic pulmonary hypertension | – | –Diagnosis on echocardiography at 36 weeks CGA using standard criteria (flat interventricular septal motion or right ventricular dilatation) |
| No chronic pulmonary hypertension | – | –Confirmed on echocardiography at 36 weeks CGA |
Who may qualify
- Ages
- 14 days and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Preterm infants will be recruited from tertiary neonatal intensive care units (NICUs) in Toronto (Mount Sinai Hospital and Sunnybrook Health Sciences Centre) and Vancouver (BC Women's Hospital \& Health Centre) Canada, the United States (University of Iowa Health Care, Iowa), and Europe (Liverpool University Hospitals NHS Foundation Trust and The Rotunda Hospital)
Key inclusion criteria (3 listed)
- Gestational age at birth ≤26+6/7 and/or birth weight <1000g
- Alive at two weeks of postnatal age
- Infant cleared by the clinical team for approach
Key exclusion criteria (3 listed)
- Known major congenital and/or genetic anomaly
- Congenital heart defects (CHD) except patent ductus arteriosus (PDA), patent foramen ovale (PFO), peripheral pulmonary artery stenosis and small (< 3 mm in diameter) ventricular septal defects
- Any condition which, in the opinion of the investigator, would preclude enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Diagnostic test characteristics calculated for TAPSE and PAAT against diagnosis of chronic pulmonary hypertension on standard diagnostic assessment
Time frame: Early diagnostic assessments (14-21 days postnatal age; 32+0/7-32+6/7); Standard diagnostic assessment (~36 weeks CGA)
Sensitivity, specificity, positive and negative likelihood ratios for TAPSE and PAAT at each early diagnostic assessment against diagnosis of chronic pulmonary hypertension on standard diagnostic assessment using echocardiography using current standard criteria
3 secondary outcomes
Composite of Death/ Chronic Neonatal Lung Disease
Time frame: Composite outcome measure will be assessed on the date of discharge for each study participant from the study Neonatal Intensive Care Unit (NICU) or date of death during admission (if applicable) up to 365 days.
Duration of need for respiratory support
Time frame: Outcome measure will be assessed on the date of discharge for each study participant from the study Neonatal Intensive Care Unit (NICU) or date of death during admission (if applicable) up to 365 days.
Length of hospital stay
Time frame: Outcome measure will be assessed on the date of discharge for each study participant from the study Neonatal Intensive Care Unit (NICU) or date of death during admission (if applicable) up to 365 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2024.
- Derived from this study: PubMed 33789855Thomas L, Baczynski M, Deshpande P, Kharrat A, Joye S, Zhu F, Ibarra-Rios D, Shah PS, Mertens L, Jankov RP, Ye XY, Neary E, Ting J, Castaldo M, Levy P, Smith A, El-Khuffash AF, Giesinger RE, McNamara PJ, Weisz DE, Jain A. Multicentre prospective observational study exploring the predictive value of functional echocardiographic indices for early identification of preterm neonates at risk of developing chronic pulmonary hypertension secondary to chronic neonatal lung disease. BMJ Open. 2021 Mar 31;11(3):e044924. doi: 10.1136/bmjopen-2020-044924.
- Individual participant dataSharing planned: No
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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.
Amish Jain, MD, PHD principal investigator
Staff Neonatologist, Clinician Scientist
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Hypertension and Infant, Premature, run by Mount Sinai Hospital, Canada at 6 sites in 4 countries.
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 3 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: finished, as of the sponsor's last update on 14 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada, United States, Ireland, United Kingdom. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Diagnostic test characteristics calculated for TAPSE and PAAT against diagnosis of chronic pulmonary hypertension on standard diagnostic assessment (time frame: Early diagnostic assessments (14-21 days postnatal age; 32+0/7-32+6/7); Standard diagnostic assessment (~36 weeks CGA)). 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 NCT04402645, 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 14 Jun 2024.