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

NCT04402645 | Completed

• 1 other identifier: 16-0111-E
• Study Type: observational
• Target: 350
• Locations: 4 countries
• Sites: 6

Brief 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 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.

Conditions

Pulmonary Hypertension; Infant, Premature

Keywords

Premature Infant; Pulmonary Hypertension; Echocardiography; Extremely Low Birth Weight Neonate; Pulmonary Vascular Resistance; Right Ventricular Function

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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

  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

  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.

Study Arms (2)

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

Eligibility Criteria

• Age: 14 Days+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• Sunnybrook Health Sciences Centre: collaborator
• Liverpool Women's NHS Foundation Trust: collaborator
• The Rotunda Hospital: collaborator
• University of Iowa: collaborator
• BC Women's Hospital & Health Centre: collaborator

Study Sites (6)

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

Location

BC Women's Hospital & Health Centre

Vancouver, British Columbia, V6H 3N1, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Rotunda Hospital

Dublin, 1 DO1 P5W9, Ireland

Location

Liverpool

Liverpool, L8 7SS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33789855 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary; Premature Birth

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Amish Jain, MD, PHD

  Staff Neonatologist, Clinician Scientist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: May 27, 2020
• Study Start: August 31, 2017
• Primary Completion: August 31, 2022
• Study Completion: April 1, 2024
• Last Updated: June 14, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CA (3); GB (1); IE (1)