Non-invasive Objective Assessment of Hemodynamics in Preterm Neonates (NOAH)

Non-invasive Objective Assessment of Hemodynamics in Preterm Neonates - the NOAH Study

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.

Study Overview

• Status: Terminated
• Conditions: Intraventricular Hemorrhage; Hemodynamic Instability; Hypotension and Shock; Hypoperfusion; Cardiac Function; Circulatory Transition
• Intervention / Treatment: Device: Multimodal objective non-invasive Monitoring

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 Type: Observational
• Enrollment (Actual): 56

Contacts and Locations

• Study Contact: Name: Christoph E Schwarz, MD; Phone Number: +353 21 4205049; Email: christoph.schwarz@ucc.ie
• Study Contact Backup: Name: Jean Conway; Email: j.conway@ucc.ie

Study Locations

• Ireland
  • Cork, Ireland
    • Neonatal Unit Cork University Maternity Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 minute to 20 hours (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Preterm Neonates born at a gestational age of 23 weeks 0 days to 31 weeks 6 days.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Feasibility/Accuracy/Reproducibility; 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.	Device: Multimodal objective non-invasive Monitoring; Multimodal objective non-invasive monitoring including cerebral oxygenation (NIRS), pulse oximetry with Pulsatility Index (PI) and non-invasive Cardiac Output Monitoring will be recorded but not used for clinical decision making. 2 ECHOs will be performed (one within the first 24h, one in the 2nd 24 hours after birth)
Prediction of Circulatory Failure; 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.	Device: Multimodal objective non-invasive Monitoring; Multimodal objective non-invasive monitoring including cerebral oxygenation (NIRS), pulse oximetry with Pulsatility Index (PI) and non-invasive Cardiac Output Monitoring will be recorded but not used for clinical decision making. 2 ECHOs will be performed (one within the first 24h, one in the 2nd 24 hours after birth)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Outcome of Circulatory Failure	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.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of non-invasive Cardiac Output Monitoring and Pulsatility Index	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	48 hours
Reproducibility of absolute left ventricular cardiac output estimated by echocardiography compared to cardiac output estimated by non-invasive Cardiac Output Monitoring	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.	48 hours
Reproducibility of left ventricular cardiac output indexed to bodyweight estimated by echocardiography compared to cardiac output estimated by non-invasive Cardiac Output Monitoring	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.	48 hours
Reproducibility of left ventricular stroke volume estimated by echocardiography compared to cardiac output estimated by non-invasive Cardiac Output Monitoring	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.	48 hours
Reproducibility of absolute right ventricular cardiac output indexed to bodyweight estimated by echocardiography compared to cardiac output estimated by non-invasive Cardiac Output Monitoring	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.	48 hours
Reproducibility of right ventricular cardiac output indexed to bodyweight estimated by echocardiography compared to estimation by non-invasive Cardiac Output Monitoring	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.	48 hours
Reproducibility of left ventricular systolic time interval ratio estimated by non-invasive Cardiac Output Monitoring compared to echocardiography	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.	48 hours
Reproducibility of absolute superior vena cava flow estimated by non-invasive Cardiac Output Monitoring compared to estimation by echocardiography	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.	48 hours
Reproducibility of superior vena cava flow indexed to bodyweight estimated by non-invasive Cardiac Output Monitoring compared to estimation by echocardiography	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.	48 hours
Correlation of non-invasive Cardiac Output Monitoring with echocardiography	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].	48 hours
Prediction of response to volume/red-blood cell transfusion by Corrected Flow Time estimated with non-invasive Cardiac Output Monitoring	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.	48 hours
Prediction of response to volume/red-blood cell transfusion by St roke Volume Variation estimated with non-invasive Cardiac Output Monitoring	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.	48 hours
Prediction of Prediction of response to inotropes by non-invasive Cardiac Output Monitoring response to therapy by non-invasive Cardiac Output Monitoring	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.	48 hours
Correlation with definitions of hypotension	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)	48 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Burden of clinical suspicion indicating Circulatory Insufficiency	Onset and duration of clinical suspicion of Circulatory Insufficiency in clinical examination (i.e. skin colour, increased capillary refill time>3seconds) as documented in the clinical charts.	48 hours
Burden of Laboratory parameters indicating Circulatory Insufficiency	Onset and duration of circulatory insufficiency indicated by laboratory parameters (metabolic acidosis with pH<7,2 Lactate>3mmol/L not explainable by intrapartum complications)	48 hours
Burden and Onset of Hypotension indicating Circulatory Insufficiency	Time spend with Mean Arterial Blood Pressure (MABP) below 30mmHG and/or MABP below gestational age in weeks	48 hours
Burden of Cerebral Oxygenation indicating Circulatory Insufficiency	Time spend wit cerebral regional tissue Saturation (rcStO2) below a value of 60% and/or rcStO2/fraction of tissue oxygen extraction (rcFtO2E) below the infants median value-5%	48 hours
Burden of Low Cardiac Output indicating Circulatory Insufficiency	Time spend with Cardiac Output in the lower quartile of the Cohort.	48 hours
Burden of impaired cerebral Autoregulation	Time spend with pressure passivity of cerebral regional tissue oxygenation (MABP and or Pulse Pressure to rcStO2/rcFtO2E). Adjusted mutual information and transfer entropy will be used to quantify coupling between MABP or pulse pressure and rcStO2 or rcFtO2E.	48 hours

Collaborators and Investigators

• Sponsor: University College Cork
• Collaborators: Osypka Medical, Berlin, Germany
• Investigators: Principal Investigator: Eugene M Dempsey, MD, UCC

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2019
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): May 31, 2021

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: September 2, 2020
• First Posted (Actual): September 3, 2020

Study Record Updates

• Last Update Posted (Actual): January 27, 2023
• Last Update Submitted That Met QC Criteria: January 25, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: objective hemodynamic multimodal Monitoring; premature preterm infant
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Hemorrhage; Hypotension
• Other Study ID Numbers: ED001/19UCC

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
• product manufactured in and exported from the U.S.: No