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

Pulmonary Hypertension Clinical Trial

Official title:

Early Identification of Preterm Neonates With Evolving Chronic Pulmonary Hypertension: Utility of Functional Echocardiographic Markers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04402645
• Other study ID #: 16-0111-E
• Status: Completed
• Start date: August 31, 2017
• Est. completion date: April 1, 2024

Study information

• Verified date: February 2024
• Source: Mount Sinai Hospital, Canada
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: April 1, 2024
• Est. primary completion date: August 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Days and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Infant, Premature
• Pulmonary Hypertension

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BC Women's Hospital & Health Centre	Vancouver	British Columbia
Ireland	Rotunda Hospital	Dublin
United Kingdom	Liverpool	Liverpool
United States	University of Iowa Health Care	Iowa City	Iowa

Sponsors (6)

Lead Sponsor	Collaborator
Mount Sinai Hospital, Canada	BC Women's Hospital & Health Centre, Liverpool Women's NHS Foundation Trust, Sunnybrook Health Sciences Centre, The Rotunda Hospital, University of Iowa

Countries where clinical trial is conducted

United States,  Canada,  Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	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.
Secondary	Duration of need for respiratory support	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.
Secondary	Length of hospital stay	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.