Impact of Nebulized Dornase Alpha on Mechanically Ventilated Patients

Inhaled Dnase (Pulmozyme®) as a Non-Invasive Treatment of Atelectasis in Mechanically Ventilated Patients

The investigators hypothesized that dornase alpha, administered twice a day (BID) by in-line nebulizer, would improve oxygenation, compliance, and time to extubation in adult patients receiving mechanical ventilation.

Study Overview

• Status: Completed
• Conditions: Atelectasis; Ventilation, Mechanical
• Intervention / Treatment: Drug: Saline; Drug: Pulmozyme (nebulized dornase alpha)

Detailed Description

Background: Lobar or segmental collapse of the lung in mechanically ventilated patients is a relatively common occurrence in the Intensive Care Unit. Available treatments are either labor or time intensive and not highly effective.

Methods: We conducted a randomized, placebo-controlled, double-blind pilot study to determine whether nebulized recombinant human dornase alpha (Pulmozyme, Genentech) improves radiologic and clinical outcomes in ventilated patients with lobar atelectasis. Outcomes of interest were chest radiograph score, oxygenation, lung compliance, and rate of extubation over the first 5 days. The groups consisted of 14 intervention patients and 16 control patients. They were similar with respect to basic demographics, age, gender, and use of therapeutic modalities relating to lung function. Baseline average chest x-ray scores, Pa02/FI02 ratios, and static compliance were not significantly different. Analysis was limited to the first 5 days.

Results: There was a significant improvement in oxygenation for the intervention group at day 5 (p=0.03). There were no significant differences in chest radiograph score, compliance, or rate of extubation. Two patients died in the intervention group, whereas none died in the control group (NS).

Conclusions: These pilot data suggest that inhaled dornase alpha appears to be safe and is associated with improved oxygenation 5 days after initiation of therapy in mechanically ventilated patients compared to placebo. Larger studies are needed to confirm these findings and determine if this intervention decreases ICU morbidity and mortality.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Newark, New Jersey, United States, 07183
      • University of Medicine and Dentistry of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• current ventilator use
• onset of lobar or whole lung collapse over the previous 12 hours
• age greater than 18

Exclusion Criteria:

• quadriplegia or debilitating neuromuscular condition
• chronic ventilator dependence
• pneumothorax
• frank hemoptysis
• elevated intracranial pressure
• intracranial bleed
• pregnancy or active nursing
• concurrent use of other investigational drugs
• history of allergy to Pulmozyme®, Chinese Hamster Ovary-derived biologics, or any of the components of the active or placebo formulations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Nebulized saline; patients on mechanical ventilation who were randomized to receive a placebo comparator (vehicle solution for dornase alpha)	Drug: Saline; Saline packaged identically to the dornase alpha intervention unit doses and coded for blinding by the company providing the intervention drug (dornase alpha).
Active Comparator: dornase alpha; patients on mechanical ventilation who were randomly assigned to receive dornase alpha by in-line nebulization	Drug: Pulmozyme (nebulized dornase alpha); nebulized dornase alpha: 2.5 mg by in-line nebulizer BID; Other Names: Pulmozyme; DNase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total Chest X Ray Score	Days 0-30

Secondary Outcome Measures

Outcome Measure	Time Frame
Oxygenation (Pa02/FI02)	Days 0-30
Static Lung Compliance	Days 0-30
Time to Extubation	Days 0-30

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Investigators: Principal Investigator: Jessica N Zitter, MD, MPH, UMDNJ, Department of Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: July 28, 2009
• First Submitted That Met QC Criteria: March 29, 2010
• First Posted (Estimate): March 30, 2010

Study Record Updates

• Last Update Posted (Estimate): March 30, 2010
• Last Update Submitted That Met QC Criteria: March 29, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Mechanical Ventilation; oxygenation; Extubation; chest x ray; dornase alpha
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pulmonary Atelectasis
• Other Study ID Numbers: 0120030304