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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Infections
• Intervention / Treatment: Drug: Placebo; Drug: Dornase alfa

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital NICU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 4 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
SHAM_COMPARATOR: 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.	Drug: Placebo; No therapy will be given to placebo arm; Other Names: Sham therapy
ACTIVE_COMPARATOR: Dornase alfa; Dornase alfa 2.5 mg nebulized endotracheally every 12 hours for 7 days or until extubation	Drug: Dornase alfa; 2.5 mg nebulized endotracheally every 12 hours for 7 days or until extubation; Other Names: Pulmozyme

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): January 1, 2015
• Study Completion (ACTUAL): April 30, 2017

Study Registration Dates

• First Submitted: March 29, 2011
• First Submitted That Met QC Criteria: May 18, 2011
• First Posted (ESTIMATE): May 19, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 7, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: ventilator associated pulmonary infections
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: Z4962s

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED