Novel Echocardiographic Methods for Early Identification of Neonates at Risk for Chronic Pulmonary Hypertension

June 13, 2024 updated by: Mount Sinai Hospital, Canada

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

350

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3N1
        • BC Women's Hospital & Health Centre
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital
  • Ireland
      • Dublin, Ireland, 1 DO1 P5W9
        • Rotunda Hospital
  • United Kingdom
      • Liverpool, United Kingdom, L8 7SS
        • Liverpool
  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Health Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 weeks and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

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)

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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 the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Early diagnostic assessments (14-21 days postnatal age; 32+0/7-32+6/7); Standard diagnostic assessment (~36 weeks CGA)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
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.
Total duration of need (number of days) for invasive, non-invasive and supplemental (low-flow) oxygen support
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.
Length of NICU admission from birth to discharge (number of days)
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mount Sinai Hospital, Canada

Collaborators

Sunnybrook Health Sciences Centre
University of Iowa
The Rotunda Hospital
BC Women's Hospital & Health Centre
Liverpool Women's NHS Foundation Trust

Investigators

  • Principal Investigator: Amish Jain, MD, PHD, Staff Neonatologist, Clinician Scientist

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 31, 2017

Primary Completion (Actual)

August 31, 2022

Study Completion (Actual)

April 1, 2024

Study Registration Dates

First Submitted

May 13, 2020

First Submitted That Met QC Criteria

May 20, 2020

First Posted (Actual)

May 27, 2020

Study Record Updates

Last Update Posted (Actual)

June 14, 2024

Last Update Submitted That Met QC Criteria

June 13, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-0111-E

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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