Pulmonary Infections
Conditions
Keywords
ventilator associated pulmonary infections
Brief summary
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.
Interventions
DRUGDornase alfa
2.5 mg nebulized endotracheally every 12 hours for 7 days or until extubation
DRUGPlacebo
No therapy will be given to placebo arm
Sponsors
Genentech, Inc.
Georgetown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Days to 4 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in Oxygen Requirement From Baseline | First week of treatment or extubation | Change in required supplemental oxygen from baseline or time to extubation from mechanical ventilation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Elimination of White Blood Cells and Bacteria From Tracheal Aspirate | During first week of treatment or until extubation whichever is earlier | 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 |
| Number of Infants Requiring Ventilator Support | 7 days | number of infants extubated during treatment/sham |
Countries
United States
Participant flow
Recruitment details
Medstar Georgetown University Hospita NICU patients recruited from May 2012 to november 2014
Pre-assignment details
No enrolled participants were excluded prior to assignment to groups
Participants by arm
| Arm | Count |
|---|---|
| Sham Placebo 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.
Placebo: No therapy will be given to placebo arm | 5 |
| Dornase Alfa Dornase alfa 2.5 mg nebulized endotracheally every 12 hours for 7 days or until extubation
Dornase alfa: 2.5 mg nebulized endotracheally every 12 hours for 7 days or until extubation | 6 |
| Total | 11 |
Baseline characteristics
| Characteristic | Dornase Alfa | Sham Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 33 days | 29 days | 31 days |
| Region of Enrollment United States | 6 participants | 5 participants | 11 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 |
Outcome results
Primary
Percent Reduction in Oxygen Requirement From Baseline
Change in required supplemental oxygen from baseline or time to extubation from mechanical ventilation
Time frame: First week of treatment or extubation
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sham Placebo | Percent Reduction in Oxygen Requirement From Baseline | 5.4 percentage FiO2 |
| Dornase Alfa | Percent Reduction in Oxygen Requirement From Baseline | 16.5 percentage FiO2 |
Secondary
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
Time frame: During first week of treatment or until extubation whichever is earlier
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sham Placebo | Elimination of White Blood Cells and Bacteria From Tracheal Aspirate | 1 participants |
| Dornase Alfa | Elimination of White Blood Cells and Bacteria From Tracheal Aspirate | 4 participants |
Secondary
Number of Infants Requiring Ventilator Support
number of infants extubated during treatment/sham
Time frame: 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sham Placebo | Number of Infants Requiring Ventilator Support | 1 participants |
| Dornase Alfa | Number of Infants Requiring Ventilator Support | 0 participants |