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Infection, Sepsis and Meningitis in Surinamese Neonates (InSepSur)

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ClinicalTrials.gov Identifier: NCT02486783
Recruitment Status : Completed
First Posted : July 1, 2015
Last Update Posted : October 21, 2016
Sponsor:
Collaborator:
University Medical Center Groningen
Information provided by (Responsible Party):
Rens Zonneveld, Academic Hospital Paramaribo

Brief Summary:

Suriname is a small developing country in South America with a population of half a million people. Early neonatal death in Suriname is high with 16 per 1000 live births. Unpublished data from the Suriname Perinatal and Infant Mortality Survey estimate contribution of infection to early neonatal mortality at 25% (4 per 1000 live births) of all deaths. In comparison, incidence rates of neonatal sepsis alone are 3.5 per 1000 live births. These numbers indicate an increased burden of neonatal infection in Suriname versus the U.S. In any case about 40 newborns that die each year of infection are a huge loss, also considering the small Surinamese community. Despite this overall idea on the impact of infectious disease in Surinamese neonates exact information regarding incidence, type of infection (e.g., localized, viral, early-onset or late-onset sepsis), risk factors (e.g., insufficient antenatal care, maternal Group B-Streptococcus status), etiology, microbial causes, morbidity, antibiotic treatment (type and duration), and epidemiological determinants (e.g., gestational age, sex, ethnicity) are lacking.

From a clinical perspective, there is still a challenge to identify neonates with infection. Neonates are often admitted with ambivalent clinical symptoms and receive preventive antibiotics that are costly, promote pathogen-resistance, and have negative long-term effects (i.e., on the development of the intestinal bacterial flora). Currently, assessment of blood leukocyte or trombocyte counts and levels of CRP are insufficiently sensitive to be used as biomarkers, while confirmation of actual sepsis or meningitis by positive culture results is relatively rare (0.5-3% in the United States). This complicates decisions on duration of antibiotic treatment and hospitalization significantly, while no other biomarkers exist.

The circulating isoforms of adhesion molecules (cAMs), which mediate interactions of leukocytes with the vascular endothelium, have been proposed as biomarkers for infection and sepsis. During infection they accumulate in the bloodstream as a result of shedding, which represents their removal from cell surfaces of endothelial cells and leukocytes by enzymes called sheddases. Recently, we have reviewed mechanisms behind shedding of cAMs in neonatal, pediatric and adult sepsis. The shedding process reflects a critical and active process in orchestrating interaction between leukocytes and the endothelium for an effective host response, while minimizing collateral tissue damage. As a result, both plasma levels of cAMs and their sheddases are subject to change during infection and sepsis. Additionally, compelling, albeit limited, data suggest changes of levels of cAMs in CSF in adult and pediatric meningitis.

To date, some evidence exists of changes in levels of cAMs during malaria (in children from Malawi) and sepsis, although not sensitive enough to predict outcomes in the clinic. Those levels have never been assessed simultaneously with levels of their sheddases in blood or CSF as a diagnostic tool. We propose that this combined approach may provide more detailed information about the extent of inflammatory activation in neonates.While a balance in levels is maintained under resting conditions or mild (local) infection, it may be perturbed during sepsis or meningitis . Thus, simultaneous measurement of these levels could promote early identification of infection, and may even distinguish between mild infection, systemic infection or meningitis. Currently, manufacturers are rapidly developing Luminex® technology as an advanced, fast, high-throughput and clinically feasible bedside tool for such an approach.

We hypothesize that incidence rates of neonates with infection in Suriname are high. We further hypothesize that, upon signs of infection, the simultaneous measurement of cAMs and their SEs in serum and CSF discriminates between infected and non-infected neonates. We aim to: 1) identify and follow neonates at the Academic Hospital Paramaribo with signs of infection to establish incidence rates of infection, and 2) investigate diagnostic potential of our proposed biomarker combination in these neonates for infection, type of infection (e.g., local (mild), sepsis or meningitis) and outcomes.


Condition or disease
Neonatal Sepsis Neonatal Infection Neonatal Meningitis

  Show Detailed Description

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Study Type : Observational
Actual Enrollment : 190 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Infection, Sepsis and Meningitis in Surinamese Neonates
Study Start Date : May 2015
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Meningitis Sepsis

Group/Cohort
Baseline controls (no signs of infection)
Neonates admitted for serial blood draws for uncomplicated hyperbilirubinemia
Signs of infection A
No infection: antibiotics stopped after 48 hours; negative cultures
Signs of infection B
Clinical infection: 7 day antibiotics; negative cultures
Signs of infection C
Sepsis: positive bacterial blood culture
Signs of infection D
Meningitis: positive bacterial CSF culture



Primary Outcome Measures :
  1. Presence of infection upon signs of infection [ Time Frame: Within 7 days ]
    Descision on duration of antibiotics (48 hours or 7 days) and blood and liquor culture results


Secondary Outcome Measures :
  1. Infection related mortality [ Time Frame: 7 day and 30 day ]
  2. Overall mortality due to infection [ Time Frame: 1 year ]

Biospecimen Retention:   Samples Without DNA
Serum samples


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 1 Month   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Newborns at the Academic Hospital Paramaribo without signs of infection (baseline controls) and with signs of infection admitted for infection work up and antibiotic treatment.
Criteria

Inclusion Criteria:

This study aims to include all neonates presenting here and at the high and medium care facilities with clinical signs of infection, sepsis or meningitis (age: 0-1 month) that require infection work up (i.e., laboratory testing and culturing):

  • Baseline controls: uncomplicated jaunice, no other signs of infection
  • Clinical signs of infection: tachypnea, dyspnea, apnea, grunting, tachycardia, bradycardia, hypotension, poor perfusion, vomitus, abdominal distension, constipation, poor feeding, lethargy, irritability, convulsions, temperature instability, pale, yellow, bleak, petechiae, bruising, bleeding.

Exclusion Criteria:

  • Extreme prematurity: gestational below 32 weeks of gestational age
  • Extreme dysmaturity: birthweight below 1500 grams
  • Maternal HIV or malignancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02486783


Locations
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Suriname
Academic Hospital Paramaribo
Paramaribo, Suriname
Sponsors and Collaborators
Academic Hospital Paramaribo
University Medical Center Groningen
Investigators
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Study Director: Grietje Molema, PhD University Medical Center Groningen, The Netherlands

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Rens Zonneveld, MD, Academic Hospital Paramaribo
ClinicalTrials.gov Identifier: NCT02486783     History of Changes
Other Study ID Numbers: VG 021-14A
First Posted: July 1, 2015    Key Record Dates
Last Update Posted: October 21, 2016
Last Verified: October 2016

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Sepsis
Toxemia
Meningitis
Neonatal Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Infant, Newborn, Diseases