Dornase Alfa Therapy for Ventilator Associated Lung Infections in the Neonatal Intensive Care Unit (NICU)

Study Overview
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Brief Summary
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To evaluate the effect of Dornase alfa on preterm and late preterm neonates with ventilator associated pulmonary infections. Dornase alfa has been effective in the treatment of pulmonary infections in patients with cystic fibrosis by aiding mucus clearance. The bacteria causing pulmonary infections in cystic fibrosis patients is similar to those infecting preterm infants. The investigators expect that dornase alfa therapy will improve recovery from ventilator associated pulmonary infections in preterm infants.

Official Title
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Pilot Study of Dornase Alfa (Pulmozyme) Therapy for Acquired Ventilator Associated Infection in Preterm and Late Preterm Infants in the Neonatal Intensive Care Unit

Conditions
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Pulmonary Infections

Intervention / Treatment
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* Drug: Dornase alfa
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infants less than 38 weeks gestation and over 7 days of age infants with a ventilator associated pulmonary infection, defined as intubated infants who have moderate to heavy White Blood Cells (WBCs) on tracheal aspirate, organisms on tracheal aspirate gram stain, a positive endotracheal tube culture, a chest x-ray with infiltrate, consolidation or atelectasis, an increase in oxygen (FiO2) requirement and whom the clinical team decides to treat with systemic antibiotic therapy Exclusion Criteria: Extremely ill infants not expected to survive Critically ill infants requiring high frequency ventilation Infants with congenital pneumonia Infants with congenital malformations of the respiratory system (e.g. Congenital diaphragmatic hernia, cystic adenomatoid malformation or tracheo-esophageal fistula) Cyanotic congenital heart disease, chromosomal abnormalities and infants with a positive newborn screen for cystic fibrosis

Ages Eligible for Study
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Minimum Age: 7 Days
Maximum Age: 4 Months

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham placebo<br>No therapy will be given to placebo arm. Respiratory therapist will shield infant from view and nebulize saline solution into incubator rather than into ventilator circuit. | Drug: Placebo<br>* No therapy will be given to placebo arm<br>* Other names: Sham therapy;|
| Active Comparator: Dornase alfa<br>Dornase alfa 2.5 mg nebulized endotracheally every 12 hours for 7 days or until extubation | Drug: Dornase alfa<br>* 2.5 mg nebulized endotracheally every 12 hours for 7 days or until extubation<br>* Other names: Pulmozyme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Reduction in Oxygen Requirement From Baseline | Change in required supplemental oxygen from baseline or time to extubation from mechanical ventilation | First week of treatment or extubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elimination of White Blood Cells and Bacteria From Tracheal Aspirate | Number of infants with Tracheal aspirate WBC present on review of smear at end of therapy Bacterial load judged on presence of positive or negative culture in Tracheal aspirate | During first week of treatment or until extubation whichever is earlier | 
| Number of Infants Requiring Ventilator Support | number of infants extubated during treatment/sham | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ventilator associated pulmonary infections