Postnatal Steroids Effects on Cardiac Function in Extremely Preterm (SPEC)

"Surveillance of Postnatal Steroids Effects on Cardiac Function in Extremely Preterm Infants With Evolving BPD: the SPEC Study."

Hypothesis/Study question

In infants born at less than 29 weeks of estimated gestational age, what are the effects of dexamethasone use on cardiac structure/performance and lung water content?

Study objectives

To measure effects before and after dexamethasone administration on cardiac structure/performance will be evaluated by using the M-mode technique (Devereux method (25-27) and lung water content will be specifically determined by the degree of water retention in premature lungs assessed by lung ultrasound at the pre specified time points.

Methodology / Study design

Single center, prospective observational cohort study planning to enroll eligible patients over a period of 12 months

Study Overview

• Status: Recruiting
• Conditions: Left Ventricular Hypertrophy
• Intervention / Treatment: Other: Echocardiography (ECHO) and lung ultrasound (LUS) studies before and after Dexamethasone administration

Detailed Description

This study investigates the effects of dexamethasone on cardiac structure/performance and lung water content in the extremely preterm population undergoing treatment for significant lung disease. For that, the specific aims are to determine the occurrence, evolution over time and possible hemodynamic impact of left ventricular hypertrophy and occurrence and degree of water retention in premature lungs, after dexamethasone administration. As secondary outcomes, this study also investigates the effects of dexamethasone on the ductus arteriosus, body growth, and autonomic regulation heart rate variability, as well as other important outcomes outlined in this protocol.

This study hypothesize that in some infants dexamethasone will be associated with the occurrence of early and/or prolonged left ventricular hypertrophy, which may be associated with changes in cardiac performance. It also hypothesize that the anti-inflammatory effects of dexamethasone would improve inflammation of immature lungs, leading to a decrease in interstitial fluid.

• Study Type: Observational
• Enrollment (Estimated): 21

Contacts and Locations

• Study Contact: Name: Gabriel Altit; Phone Number: 5144124453; Email: gabriel.altit@mcgill.ca
• Study Contact Backup: Name: Jessica Simoneau; Phone Number: 5144124453; Email: jessica.simoneau@muhc.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Montreal Children's hospital, Mcgill University Health Centre
      • Contact: Gabriel Altit, MD; Phone Number: 514-412-4452; Email: gabriel.altit@mail.mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 minute and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Extreme premature babies (< 29 weeks of gestational age at birth) undergoing first treatment with dexamethasone for significant lung disease at the neonatal intensive care.

Description

Inclusion Criteria:

• < 29 weeks of gestational age at birth admitted at the McGill University Children Hospital's neonatal intensive care unit
• To be initiated on dexamethasone therapy for treatment of significant lung disease as per medical team decision.

Exclusion Criteria:

• Congenital heart disease (except: Atrial septum defect (ASD), Ventricular septum defect (VSD)
• Major congenital anomalies/genetic disorder (Trisomy 13, 18, 21)
• Congenital severe lung or airway malformation (Trachea-esophageal fistula, congenital pulmonary airway malformation, congenital diaphragmatic hernia)
• Twin-twin transfusion syndrome

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular hypertrophy (LVH) measures by M-mode (Z-Scores)	The effects of dexamethasone administration on cardiac structure/performance will be evaluated by using the M-mode technique (Devereux method (25-27) 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
Lung water content	Lung water content will be specifically determined by the degree of water retention in premature lungs assessed by lung ultrasound at the specified time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular (LV) output	The effects of dexamethasone administration on: On the LV output assessed by Doppler by echocardiography Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
LV and RV function by strain	LV and RV function by strain by post treatment of echocardiography acquired images with a Tomtec platform Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
LV ejection fraction	The effects of dexamethasone administration on: The ejection fraction measured by Simpson on a echocardiography. Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
Ductal size	The effects of dexamethasone administration on the size patent ductus arteriosus (PDA) measured on the echocardiography Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
Doppler flow velocities	The effects of dexamethasone administration on: The Doppler flow velocities measured by echocardiography Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
Measures of PDA significance	The effects of dexamethasone administration on: LA:AO (left atrium: aorta) Resistance index (RI) of the Anterior Cerebral Artery Direction of ductal flow Peak velocity of PDA in systole Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
LV mass by STE	LV mass calculation using Speckle tracking echocardiography (STE) on the Tomtec platform Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
RV function by TAPSE	The effects of dexamethasone administration on: Tricuspid annular plane systolic excursion measurement by M-Mode on the echocardiography Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
Strain and 3D values	The effects of dexamethasone administration on: RV and LV strains and on the cardiac volumes by 3 D (RV and LV) by echocardiography acquired images, using Tomtec platform for post treatment Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
Heart rate variability	The effects of dexamethasone administration on heart rate variability by ECG Time points: 0 day (before the start of dexamethasone), 3- , 7-day of treatment, 14-day of treatment if still receiving dexamethasone, and 1-week, 2-weeks after dexamethasone discontinuation, and finally at 35 - 37 weeks post menstrual age (PMA) or prior to discharge/transfer	At the time of echocardiography
Growth trajectory	The effects of dexamethasone administration on growth trajectory (body, length, head circumference, L/W ratio) at 1-,2-weekks prior treatment and 1-,2-,3-,4-,6-,8- weeks after treatment, and finally at 36 weeks PMA	At the time of the last echocardiography
Cortisol levels	The effects of dexamethasone after administration: Cortisol levels in nmol/L	At the study completion (12 months)
BPD	The effects of dexamethasone administration on: -BPD rate (%) (2018 NICHD definition)	At the study completion (12 months)
Mortality	- Rate of death in this high risk population (%)	At the study completion (12 months)
Responders and non responders to Dexamethasone	We will analyze the rate (%) of responders and non-responders to Dexamethasone. Responders: Defined by decreasing Respiratory Severity Scores (RSS) by 40% at day 6 of Dexamethasone treatment or before. RSS is calculated by using maximum of mean airway pressure (MAP) multiplied by fractional oxygen (FiO2) at the day of the first dose of Dexamethasone administration (Day 0)	At the study completion (12 months)

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Gabriel Altit, MD, Montreal Children's hospital, MUHC

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Lung ultrasound; Dexamethasone; Echocardiography; Heart rate variability; Left ventricular hypertrophy; Ductus arteriosus
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Cardiomegaly; Hypertrophy; Hypertrophy, Left Ventricular; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: 2021-7305

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