Non-invasive Objective Assessment of Hemodynamics in Preterm Neonates

Terminated

• Conditions: Hypoperfusion; Hypotension and Shock; Hemodynamic Instability; Intraventricular Hemorrhage; Circulatory Transition; Cardiac Function
• Interventions: Device: Multimodal objective non-invasive Monitoring

• Registration Number: NCT04538079
• Lead Sponsor: University College Cork

Brief Summary

Study type: Prospective Observational trial Study design: Longitudinal Population: Preterm newborns \<32 weeks gestational age Hypothesis: The inclusion of non-invasive physiological measures of cardiac output, peripheral perfusion and brain oxygenation (NIRS) for preterm neonates is feasible and reveals additional information on the hemodynamic status compared to blood pressure alone. These measurements can improve the ability to rapidly identify those infants who might benefit from intervention and are correlated with short term clinical outcomes.

Detailed Description

Understanding neonatal hemodynamics is key to neonatal care. Despite decades of research, uncertainty continues as to how best assess impaired hemodynamics.

Hypotension defined by a low Mean Arterial Blood Pressure (MABP) remains a common issue in preterm infants, affecting up to 30% of extremely preterm infants.

It is common to focus only on MABP thus neglecting the complex and dynamic (patho)physiology that may be present in newborn infants. Providing sufficient cellular oxygenation is the primary task of the circulatory system and different factors may compromise it. In this prospective observational study the investigators will examine various forms of objective non-invasive continuous hemodynamic monitoring methods in very preterm infants

1. For feasibility of non-invasive CO measurement (first 20 patients)

2. For reproducibility and correlation of this measurement and ECHOcardiography (first 40 echocardiographic examinations)

3. For prediction of therapy response.

4. For correlation with clinical definitions of hypotension/hypoperfusion

5. For prediction of later clinical problems/complications of prematurity and impaired hemodynamic status.

Study Timeline

• Study Start: 2019-11-09
• Study First Submitted: 2020-03-05
• Study First Submitted QC: 2020-09-02
• Study First Posted: 2020-09-03
• Primary Completion: 2021-05-31
• Study Completion: 2021-05-31
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-25
• Last Update Posted: 2023-01-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

• Neonates of 23 weeks 0 days to 31 weeks 6 days
• NIRS/non-invasive Cardiac Output - device available
• Parental Informed Consent

Exclusion Criteria

• Congenital anomalies
• Major cardiac defects
• Hydrops
• Parents decline to consent to the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Feasibility/Accuracy/Reproducibility	Multimodal objective non-invasive Monitoring	The first 20 participants will be analysed for feasibility and the first 40 ECHOs for accuracy/reproducibility of non-invasive Cardiac Output Monitoring with ECHO as reference Method.
Prediction of Circulatory Failure	Multimodal objective non-invasive Monitoring	Together with the Feasibility/Accuracy/Reproducibility Cohort this group's results will be analysed for prediction of circulatory failure defined as an ultrasound abnormality (IVH grade 3 - 4) or death within the first two weeks of life.

Primary Outcome Measures

Name	Time	Method
Adverse Outcome of Circulatory Failure	14 days	Correlation of clinical, laboratory, conventional and multimodal non-invasive monitoring and/or a combination of variables with ultrasound abnormality (IVH grade 3 - 4/any IVH) or death within the first two weeks of life.

Secondary Outcome Measures

Name	Time	Method
Reproducibility of absolute left ventricular cardiac output estimated by echocardiography compared to cardiac output estimated by non-invasive Cardiac Output Monitoring	48 hours	Reproducibility of cardiac output estimates by non-invasive Cardiac Output compared to echocardiographic examinations will be performed using absolute left ventricular output \[mL/min\]. The Investigators will use Bland-Altman analysis (Bland-Altman plots, Repeatability coefficient. Repeatability Index will be used for between parameter comparison.
Reproducibility of right ventricular cardiac output indexed to bodyweight estimated by echocardiography compared to estimation by non-invasive Cardiac Output Monitoring	48 hours	Reproducibility of relative right ventricular cardiac output estimates by non-invasive Cardiac Output Monitoring compared to echocardiographic examinations will be performed using right ventricular output indexed to bodyweight \[mL/kg bodyweight/min\]. The Investigators will use Bland-Altman analysis (Bland-Altman plots, Repeatability coefficient. Repeatability Index will be used for between parameter comparison.
Reproducibility of left ventricular cardiac output indexed to bodyweight estimated by echocardiography compared to cardiac output estimated by non-invasive Cardiac Output Monitoring	48 hours	Reproducibility of cardiac output estimates by non-invasive Cardiac Output compared to echocardiographic examinations will be performed using left ventricular output indexed to bodyweight \[mL/kg bodyweight/min\]. The Investigators will use Bland-Altman analysis (Bland-Altman plots, Repeatability coefficient. Repeatability Index will be used for between parameter comparison.
Reproducibility of absolute superior vena cava flow estimated by non-invasive Cardiac Output Monitoring compared to estimation by echocardiography	48 hours	Cardiac output estimates of non-invasive Cardiac Output-Monitoring and echocardiographic examinations will be compared using absolute superior vena cava flow \[mL/min\]. The Investigators will use Bland-Altman analysis (Bland-Altman plots, Repeatability coefficient. Repeatability Index will be used for between parameter comparison.
Reproducibility of superior vena cava flow indexed to bodyweight estimated by non-invasive Cardiac Output Monitoring compared to estimation by echocardiography	48 hours	Cardiac output estimates of non-invasive Cardiac Output-Monitoring and echocardiographic examinations will be compared using superior vena cava flow indexed to bodyweight \[mL/kg bodyweight/min\]. The Investigators will use Bland-Altman analysis (Bland-Altman plots, Repeatability coefficient. Repeatability Index will be used for between parameter comparison.
Prediction of response to volume/red-blood cell transfusion by Corrected Flow Time estimated with non-invasive Cardiac Output Monitoring	48 hours	Treatment Responsiveness (Volume and/or red blood cells responsiveness) using trend analysis within Corrected Flow Time (FTC \[ms\]) for volume responsiveness including a receiver operating characteristic analysis for infants who received volume and/or red blood cells during the study period. (Comparison of 20min mean as baseline before, during and 20min after treatment. Response is defined as normalization of the above mentioned physiological parameters within 20 minutes after receiving treatment.
Feasibility of non-invasive Cardiac Output Monitoring and Pulsatility Index	48 hours	The proportion of infants in whom a continuous recording of non-invasive cardiac output (CO) and perfusion index (PI) analysis was obtained for at least 24 hours during the first 48 hours after birth with a good signal quality index
Reproducibility of absolute right ventricular cardiac output indexed to bodyweight estimated by echocardiography compared to cardiac output estimated by non-invasive Cardiac Output Monitoring	48 hours	Reproducibility of absolute cardiac output estimated by non-invasive Cardiac Output Monitoring compared to echocardiographic examinations will be performed using right ventricular output \[mL/min\]. The Investigators will use Bland-Altman analysis (Bland-Altman plots, Repeatability coefficient. Repeatability Index will be used for between parameter comparison.
Reproducibility of left ventricular systolic time interval ratio estimated by non-invasive Cardiac Output Monitoring compared to echocardiography	48 hours	Reproducibility of left ventricular systolic time interval ratio estimates by non-invasive Cardiac Output-Monitoring and echocardiographic examinations will be compared using left ventricular pre-ejection period to left ventricular output time ratio \[no unit\]. The Investigators will use Bland-Altman analysis (Bland-Altman plots, Repeatability coefficient. Repeatability Index will be used for between parameter comparison.
Reproducibility of left ventricular stroke volume estimated by echocardiography compared to cardiac output estimated by non-invasive Cardiac Output Monitoring	48 hours	Reproducibility of left ventricular stroke volume estimates by non-invasive Cardiac Output compared to echocardiographic examinations will be performed using stroke volume \[mL\]. The Investigators will use Bland-Altman analysis (Bland-Altman plots, Repeatability coefficient. Repeatability Index will be used for between parameter comparison.
Correlation of non-invasive Cardiac Output Monitoring with echocardiography	48 hours	CO-Monitoring and echocardiography will be analysed for correlation using correlation coefficient analysis pairwise for left and right ventricular output indexed to bodyweight \[mL/kg bodyweight/min\], left ventricular pre-ejection period to left ventricular output time ratio and Superior Vena Cava-flow indexed to bodyweight \[mL/kg bodyweight/min\].
Prediction of response to volume/red-blood cell transfusion by St roke Volume Variation estimated with non-invasive Cardiac Output Monitoring	48 hours	Treatment Responsiveness (Volume and/or red blood cells responsiveness) using trend analysis within Stroke Volume Variation (SVV) for volume responsiveness including a receiver operating characteristic analysis for infants who received volume and/or red blood cells during the study period. (Comparison of 20min mean as baseline before, during and 20min after treatment. Response is defined as normalization of the above mentioned physiological parameters within 20 minutes after receiving treatment.
Prediction of Prediction of response to inotropes by non-invasive Cardiac Output Monitoring response to therapy by non-invasive Cardiac Output Monitoring	48 hours	Treatment Responsiveness (Inotrope) using trend analysis within left ventricular cardiac output indexed to bodyweight \[ml/kg bodyweight/min\] for inotrope responsiveness including a receiver operating characteristic analysis for infants who received inotropes during the study period. (Comparison of 20min mean as baseline before, during and 20min after initiation of inotrope treatment. Response is defined as normalization of the above mentioned physiological parameters within 20 minutes after receiving treatment.
Correlation with definitions of hypotension	48 hours	Correlation of multimodal non-invasive monitoring with commonly used definitions of hypotension (Mean Arterial Blood Pressure MABP below 30mmHG and/or MABP below gestational age in weeks)

Trial Locations

Locations (1)

Neonatal Unit Cork University Maternity Hospital; 🇮🇪 Cork, Ireland