Prediction of Intraventricular Hemorrhage Using Echocardiography and Near Infrared Spectroscopy (PIONIRS)

Moderate-severe intraventricular hemorrhage (msIVH, Grades II-IV) is a significant neurological complication among extremely low gestational age neonates (ELGANs, <=27+6 weeks) and is associated with long-term neuro-disabilities. In Canada, msIVH affects ~25-30% of the 1300 ELGANs born annually, with little change in incidence over last decade. Typically, it occurs between days 2-7 of age, providing a finite window of opportunity. Instituting therapies at the population level, however, exposes many low-risk infants to side effects, adversely affecting risk-benefit profile and requiring large sample sizes in trials. A targeted preventative approach, though ideal, is currently challenged by our inability to reliably identify at-risk ELGANs early after birth. Near-infrared spectroscopy (NIRS) has emerged as a promising non-invasive bedside neuromonitoring tool. Pilot studies using NIRS, including ours, found lower cerebral saturations (CrSO2) and greater periods of altered cerebral autoregulation in infants who later developed msIVH. However, a systematic planned investigation is needed to establish the predictive characteristics of NIRS-derived markers, using clinically translatable methods (cumulative burden over time-period vs. single time-point values) and identify their relative performance at different time-points during transition. Further, incorporating echocardiographic (ECHO) hemodynamic markers, known to be associated with msIVH, may allow for the establishment of robust multi-model prediction models and the gain of mechanistic hemodynamic insights to inform future management. Hence, our objective is to investigate the utility of multi-modal assessment using NIRS and ECHO for early identification of ELGANs at risk of msIVH, and generate clinically applicable predictive model(s).

Study Overview

• Status: Recruiting
• Conditions: Intraventricular Hemorrhage of Newborn Grade 2; Intraventricular Hemorrhage of Newborn Grade 3; Intraventricular Haemorrhage Grade IV
• Intervention / Treatment: Diagnostic test: Functional echocardiography; Diagnostic test: Head Ultrasound; Diagnostic test: Cerebral near-infrared spectroscopy

Detailed Description

The overall objective is to conduct a large, adequately powered prospective cohort study to investigate the utility of combined hemodynamic assessment using NIRS and ECHO for early identification of ELGANs at risk of developing moderate-severe IVH, and to establish clinically translatable prediction models.

The specific primary aim is to examine the discriminating characteristics of NIRS-derived parameters (CrSO2 and cerebral oxygenation index [COIx, values >0.5 indicate altered cerebral autoregulation]) at 12, 18, 24, 30, 36, 42 and 48 hours of age, individually and in combination, for identifying ELGANs who subsequently develop moderate-severe IVH. The postnatal age where NIRS may best identify at-risk ELGANs is unknown and identifying these infants early within 48 hours of age may maximize its impact for employing neuroprotective strategies.

The secondary aims are:

1. To examine if adding ECHO parameters of systemic blood flow (left ventricular output [LVO], superior vena cava [SVC] flow and PDA size) and patient demographics can improve the discriminating characteristics of NIRS and generate relevant clinical prediction models.
2. To gain mechanistic insights into pathophysiology of moderate-severe IVH, by examining associations between significant abnormalities on NIRS, as identified and ECHO markers which may impact cerebral perfusion and oxygen delivery (PDA and its size, LVO, right ventricular output and left ventricular ejection fraction).

This will be novel information as potential mechanisms governing low CrSO2 or altered autoregulation in ELGANs are not known and can potentially inform future clinical preventative strategies and help design interventional trials.

• Study Type: Observational
• Enrollment (Estimated): 380

Contacts and Locations

• Study Contact: Name: Laura Thomas, MSc; Phone Number: 172060 4165864800; Email: laura.thomas@sinaihealth.ca
• Study Contact Backup: Name: Poorva Deshpande; Phone Number: 7213 4165864800; Email: poorva.deshpande@sinaihealth.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Not yet recruiting
      • Royal Alexandra Hospital
      • Contact: Abbas Hyderi
  • Ontario
    • Calgary, Ontario, Canada
      • Not yet recruiting
      • Foothillls Medical Centre
      • Contact: Lara Leijser
    • London, Ontario, Canada
      • Not yet recruiting
      • London Health Sciences Centre
      • Contact: Soume Bhattacharya
    • Toronto, Ontario, Canada
      • Recruiting
      • Mount Sinai Hospital
      • Principal Investigator: Poorva Deshpande, MD
      • Contact: Thaiani Wulff; Email: thaiani.wulff@sinaihealth.ca
      • Contact: Phoebe Thum, MSc; Email: phoebe.thum@sinaihealth.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Preterm infants at tertiary NICU admitted to one of four study NICUs:

• Mount Sinai Hospital, Toronto (ON)
• The Children's Hospital at London Health Sciences Center, London (ON)
• Foothills Medical Centre, Calgary (AB)
• Royal Alexandra Hospital, Edmonton (AB)

Description

Inclusion Criteria:

• Preterm infants born <=27+6 weeks gestational age

Exclusion Criteria:

• Known genetic or congenital anomalies that are likely to affect cardiac or cerebral oxygenation measures
• Palliative care plan prior to or immediately following delivery

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraventricular hemorrhage (IVH) Status	IVH will be classified using Volpe's classification which is also the clinical standard for IVH classification (Grade I: Blood in germinal matrix with or without IVH less than 10% of ventricular space; Grade II: IVH occupying 10-50% of ventricular space on parasagittal view; Grade III: IVH occupying >50% of ventricle with or without ventricular echo-densities; Grade IV: periventricular hemorrhagic infarction).	Day 4-7 clinical head ultrasound

Collaborators and Investigators

• Sponsor: Mount Sinai Hospital, Canada
• Collaborators: London Health Sciences Centre; Royal Alexandra Hospital; Foothills Medical Centre
• Investigators: Principal Investigator: Poorva Deshpande, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (Actual): February 1, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Echocardiography; Near-infrared spectroscopy; Preterm neonates; Head ultrasound
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pregnancy Complications; Intracranial Hemorrhages; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hemorrhage; Cerebral Hemorrhage; Infant, Newborn, Diseases; Fetal Diseases
• Other Study ID Numbers: 486734

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