Chlorhexidine Skin Application for Prevention of Infection in Infants Weighing <1500 g at Birth

Study Overview
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Brief Summary
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Purpose of this study is determine if skin application of chlorhexidine at birth would reduce infection in infants weighing <1500 g at birth.

Detailed Description
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Background Infants weighing <1500 g at birth infants are more prone to acquire infections, often through their immature skin which serve as a portal of entry for invasive pathogens. Skin application of antiseptics such as chlorhexidine may reduce infections in these infants. However, there is a paucity of data on the safety and efficacy of such intervention in these infants. Hypothesis: Among hospitalized very low birth weight (VLBW; <1500 g) neonates, single whole body skin cleansing with 0.25% chlorhexidine within 6 hours after birth would reduce the incidence of sepsis in the first seven days of life from 25% to 17.5% (relative reduction of 30%) when compared to skin cleansing with sterile water Objectives: Primary- To evaluate the effect of whole body skin cleansing with 0.25% chlorhexidine (single application, at birth) on the incidence of sepsis (culture positive or culture negative) compared to sterile water cleansing in the first week of life in VLBW infants Secondary- to compare following outcomes in this experiment: Culture-confirmed sepsis within the first week of life Need for repeat hospital admissions within first 28 days of life Mortality within first 28 days of life Cold stress/hypothermia at 0, 5, 15 and 30 minutes of intervention Skin condition at 24 h of life Colonization rates (subset) Serum levels of chlorhexidine (subset) Methods: Eligible infants would be randomized within 6 hours of birth to either whole body skin cleansing with chlorhexidine (specially prepared wipes releasing 0.25% chlorhexidine), or sterile water (placebo). The research staff would collect the baseline data, record the axillary temperature and assess the skin condition using the Newborn Skin Condition Scoring (NSCS)score. The research team would follow the infants for development of sepsis and other outcomes. The infants would be subjected to detailed sepsis work up on clinical suspicion of sepsis, until 28 days of life. Sepsis would be defined based on combination of clinical course, indirect markers, bacterial culture results and antibiotic treatment status.

Official Title
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Whole Body Cleansing With 0.25% Chlorhexidine at Birth for Prevention of Sepsis in Infants <1500 g: a Multi-center, Blinded, Randomized Trial

Conditions
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Neonatal Sepsis, Neonatal Mortality Rate

Intervention / Treatment
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* Drug: 0.25% chlorhexidine
* Drug: sterile water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Birth weight less than 1500 g Exclusion Criteria: Birth weight <750 g Major congenital malformations Total duration of positive pressure ventilation (PPV) > 3 mins OR chest compressions Shock- requiring inotropes >10 mic/kg/min

Ages Eligible for Study
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Maximum Age: 28 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: sterile water<br>sterile water wipes | Drug: sterile water<br>* Sterile water wipes (placebo)<br>|
| Experimental: 0.25% chlorhexidine<br>0.44% chlorhexidine digluconate wipes which will release 0.25% free chlorhexidine | Drug: 0.25% chlorhexidine<br>* 0.44% chlorhexidine di-gluconate body wipes which would release 0.25% free chlorhexidine on application<br>* Other names: Chx;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sepsis within first 7 days of life | Sepsis would be defined on the basis of clinical course, lab parameters including culture results and antibiotic treatment given. | First 7 days of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Readmissions & mortality rates within neonatal period | The re-admissions & mortality rates within neonatal period in these infants will be prospectively recorded during hospital admission as well as follow up. The follow up includes telephonic contact as well as home visits and verbal autopsy in cases of deaths at home. | 28 days | 
| Body temperature at 0, 5, 15, 30 minutes after application | Axillary temperature would be monitored with thermometer at above time points for full three minutes. | 30 minutes | 
| Skin condition | Newborn Skin Condition Score (NSCS)will be used to assess the skin condition. | 24 ±6 hours | 
| Skin colonization rates | In a sub-group of infants, skin swabs will be collected at baseline and 24 ±6 hours and sent to microbiology lab; colonization rates would be determined by semi-quantitative methods. | 24 ±6 hours | 
| Chlorhexidine percutaneous absorption | Serum chlorhexidine levels will be assayed in a sub-set to assess the extent of percutaneous absorption. 5ml of blood will be stored at -80 deg. C till transport to the lab. Samples will be processed in batches as per standard protocol to determine the levels. | 48 ±6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chlorhexidine, sepsis, neonatal, whole-body skin cleansing