Stratifying Risk for Intracerebral Haemorrhage (NEW_STRATEGI)

STRATifying Risk for intracErebral haemorrhaGe and Neurodevelopmental DIsorders in Newborns

This study aims to investigates the role of gestational age on the prevalence of coagulation factors and components of the complement system in preterm- (≤32+0 weeks) and term neonates (≥37+0 weeks) and their role for the development of brain hemorrhage.

Study Overview

• Status: Unknown
• Conditions: Coagulation Protein Disorders; Preterm Birth; Coagulation Disorder Neonatal
• Intervention / Treatment: Diagnostic test: mass spectrometry (LC-MS/MS)

Detailed Description

The occurrence of brain hemorrhage (germinal matrix hemorrhage and intraventricular hemorrhage, GM-IVH) in newborns, especially in preterm infants, is one of the most important prognostic factors for mortality and morbidity (especially for later neurological development) in this collective. The risk of high-grade bleeding in extremely premature infants (22 weeks) is approx. 38% and decreases to approx. 7% by the 28th week. The total frequency of GM-IVH is around 8% in gestational weeks 23 to 31, with each additional gestational week reducing the risk by 3.5%. The etiopathology of brain hemorrhage is complex and involves both environmental and genetic factors. Recent studies particularly suggest an involvement of the immature coagulation system in preterm neonates. Global coagulation parameters, such as the International Normalized Ratio (INR), have already been associated with an increased risk of bleeding, but rarely show fluctuations outside the norm. Furthermore, polymorphisms in the area of individual coagulation factors as well as other inflammatory and vascular individual components of coagulation, are associated with an increased risk of bleeding. Mass spectrometry has long been used for the analysis of biological samples and has developed into an indispensable tool for proteomics research. The study aims to establish the mass spectrometric detection of a total of 125 blood plasma factors containing the individual components of the coagulation system and the complement system. The method enables quantitative detection of the coagulation system with even the smallest sample quantities, so that sampling can be combined with routine measures, particularly in the field of neonatology. This pilot study to compare the compositional differences regarding coagulation factors and the complement system in relation to the gestational age (i.e. preterm ≤32+0 weeks vs. term neonates ≥37+0 weeks).

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • Department of Pediatrics- and Adolescent Medicine, FAU Erlangen-Nuremberg
      • Contact: Fabian Fahlbusch; Phone Number: +49 9131 85 33118; Email: fabian.fahlbusch@uk-erlangen.de
      • Contact: Ferdinand Knieling; Phone Number: +49 9131 85 33118; Email: ferdinand.knieiling@uk-erlangen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• medical indication (newborn screening) and informed consent for blood drawing

Exclusion Criteria:

• clinical evidence of infection
• clinical evidence of hyperbilirubinemia
• Preeclampsia (PE), HELLP-syndrome, intrauterine growth restriction (IUGR) and PE+IUGR

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Term infants (≥37+0 weeks); Blood collection (5 drops) during newborn-screening (36-72h after birth) or postnatal hospitalization (<36h after birth). The blood sample will then be examined using mass spectrometry (LC-MS/MS).	Diagnostic test: mass spectrometry (LC-MS/MS); Blood collection (5 drops) during newborn-screening (36-72h after birth) or postnatal hospitalization (<36h after birth). The blood sample will then be examined using mass spectrometry (LC-MS/MS) for 125 proteins.
Experimental: Preterm infants (≤32+0 weeks); Blood collection (5 drops) during newborn-screening (36-72h after birth) or postnatal hospitalization (<36h after birth). The blood sample will then be examined using mass spectrometry (LC-MS/MS).	Diagnostic test: mass spectrometry (LC-MS/MS); Blood collection (5 drops) during newborn-screening (36-72h after birth) or postnatal hospitalization (<36h after birth). The blood sample will then be examined using mass spectrometry (LC-MS/MS) for 125 proteins.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite mass spectrometric profile of coagulation and complement factors stratified by preterm/term neonates.	Individual composite mass spectrometric profile of 125 blood plasma factors containing the individual components of the coagulation system and the complement system of term (≥37+0 SSW) compared to preterm neonates (≤32+0 SSW)	Single time point (1 day)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite mass spectrometric profile of coagulation and complement factors stratified by gestational week	Individual composite mass spectrometric profile of 125 blood plasma factors containing the individual components of the coagulation system and the complement system stratified by gestational week	Single time point (1 day)
Composite mass spectrometric profile of coagulation and complement factors stratified by gender	Individual composite mass spectrometric profile of 125 blood plasma factors containing the individual components of the coagulation system and the complement system of female compared to male neonates	Single time point (1 day)
Composite mass spectrometric profile of coagulation and complement factors correlated to body weight	Individual composite mass spectrometric profile of 125 blood plasma factors containing the individual components of the coagulation system and the complement system correlated to body weight	Single time point (1 day)
Composite mass spectrometric profile of coagulation and complement factors stratified by medication	Individual composite mass spectrometric profile of 125 blood plasma factors containing the individual components of the coagulation system and the complement system stratified by perinatal medication to non-perinatal medication.	Single time point (1 day)
Mass spectrometric profile of coagulation and complement factors correlated to CRP	Individual mass spectrometric profile of 125 blood plasma factors containing the individual components of the coagulation system and the complement system correlated to C-reaktive Protein (CRP)	Single time point (1 day)
Mass spectrometric profile of coagulation and complement factors correlated to WBC	Individual composite mass spectrometric profile of 125 blood plasma factors containing the individual components of the coagulation system and the complement system correlated to leucocyte count (WBC)	Single time point (1 day)
Composite mass spectrometric profile of coagulation and complement factors correlated to maternal age	Individual composite mass spectrometric profile of 125 blood plasma factors containing the individual components of the coagulation system and the complement system correlated to maternal age	Single time point (1 day)
Composite mass spectrometric profile of coagulation and complement factors correlated to placental weight	Individual composite mass spectrometric profile of 125 blood plasma factors containing the individual components of the coagulation system and the complement system correlated to placental weight	Single time point (1 day)

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Principal Investigator: Fabian B Fahlbusch, M.D., Department for Children- and Adolescent Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2019
• Primary Completion (Anticipated): September 30, 2020
• Study Completion (Anticipated): September 30, 2020

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 28, 2019

Study Record Updates

• Last Update Posted (Actual): October 28, 2019
• Last Update Submitted That Met QC Criteria: October 23, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: ICH; Neonatal; LC-MS/MS; Preterm; Coagulation; IVH
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hematologic Diseases; Hemorrhagic Disorders; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Intracranial Hemorrhages; Hemostatic Disorders; Blood Coagulation Disorders; Disease; Hemorrhage; Premature Birth; Cerebral Hemorrhage; Coagulation Protein Disorders
• Other Study ID Numbers: 294_19B

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