A Pilot Randomized Controlled Trial for Antibiotic Exposure in Neonatal Sepsis Using Neutrophil CD64

Study Overview
=================
Brief Summary
-----------------
Unnecessary and prolonged antibiotic therapy in newborn babies can have serious consequences including development of necrotizing enterocolitis (a serious, potentially life-threatening gastrointestinal illness in premature babies), late-onset infections, resistance to antibiotics, increased length of hospital stay, and death. Starting and continuing antibiotic therapy for blood culture-negative infections in the neonatal intensive care unit (NICU) is fairly common with numbers of such patients varying from 20%-90% of infants undergoing a sepsis evaluation in the NICU. While blood culture results are the gold standard, there is usually a delay of up to 48-72h before the results are known. Hence, initiation and continuation of antibiotic treatment are usually based on clinical evaluation and blood count criteria which do not possess high specificity or sensitivity, and may be unreliable in the first few hours after birth or in the early stages of infection. Since the investigators found that neutrophil CD64 (a type of protein found on the surface of a type of white blood cell that can be detected quickly in a very small amount of blood sample) has high accuracy for early detection of blood culture-proven infections in newborn babies, with extremely high negative predictive value (can identify babies definitively with no infection), the investigators will use this test to decide whether to stop or continue antibiotics in the NICU. The investigators hypothesis is that neutrophil CD64 values can be safely used to discontinue antibiotics in newborns suspected of having infections. The investigators aims are to utilize sequential measurements of CD64 values to stop antibiotics early in neonates being investigated for both early and late-onset infections in the NICU. This is a prospective, randomized, controlled (RCT) trial. The study population will be derived from the sub-set of all newborn infants who have undergone investigations for presence of infection in the NICU.

Official Title
-----------------
A Pilot Randomized Controlled Trial for Antibiotic Exposure in Neonatal Sepsis Using Neutrophil CD64

Conditions
-----------------
Neonatal Early-onset Sepsis, Neonatal Late-onset Sepsis

Intervention / Treatment
-----------------
* Other: Intervention is to stop antibiotics at 24h .


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants undergoing a sepsis evaluation in the NICU Exclusion Criteria: They have a major life-threatening congenital malformation The attending neonatologist has objections to the infant participating in the study

Ages Eligible for Study
-----------------
Minimum Age: 1 Hour
Maximum Age: 5 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control (continue antibiotics) group<br>The antibiotics will be continued for at least another 24h i.e. for 48h, pending blood culture results at 48h, as per standard practice in the NICU. | |
| Active Comparator: Study (discontinue antibiotics) group<br>The intervention is to discontinue antibiotics at 24h, and he/she will be kept under observation in the NICU for at least an additional 24h, pending blood culture results at 48h. | Other: Intervention is to stop antibiotics at 24h .<br>* Stoppage of antibiotics at 24h in the intervention arm, randomization based on neutrophil CD64 values.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of infants with early-onset sepsis (EOS) and late-onset sepsis (LOS) randomized to either stopping or continuing antibiotics at 24h, based on the neutrophil CD64 measurement |  | At 48h after initiation of antibiotics. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Neutrophil CD64 Index value in neonates with/without exposure to antibiotics from 24h to 48h. |  | At 48h after initiation of antibiotics. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Infant, Infection, Newborn, Antibiotics, Neutrophil CD64, Blood Culture