PIEONIRS: Prediction of Intraventricular Hemorrhage Using Echocardiography and Near Infrared Spectroscopy

Sponsor

Mount Sinai Hospital, Canada (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05708105

Collaborator

London Health Sciences Centre (Other), Foothills Medical Centre (Other), Royal Alexandra Hospital (Other)

380

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Moderate-severe intraventricular hemorrhage (Grades II-IV, msIVH) is a significant neurological complication among extremely low gestational age neonates (ELGANs, <27+6 weeks) and is associated with long-term neurodisabilities. 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).

Condition or Disease	Intervention/Treatment	Phase
Intraventricular Hemorrhage of Newborn Grade 2 Intraventricular Hemorrhage of Newborn Grade 3 Intraventricular Haemorrhage Grade IV	Diagnostic Test: Cerebral near-infrared spectroscopy Diagnostic Test: Functional echocardiography Diagnostic Test: Head Ultrasound

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:

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.
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 Design

Study Type:

Observational

Anticipated Enrollment :

380 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Prediction of Intraventricular Hemorrhage Using Echocardiography and Near Infrared Spectroscopy

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2026

Anticipated Study Completion Date :

Nov 1, 2027

Outcome Measures

Primary Outcome Measures

Moderate-severe IVH (Grade II/III/IV) [Day 4-7 clinical head ultrasound]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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