Dornase Alpha Versus Hypertonic Saline for Lung Atelectasis in Non-Cystic Fibrosis Patients

Dornase Alpha Versus Hypertonic Saline for Lung Atelectasis

Despite the lack of trials proving the efficacy of DNase in non cystic fibrosis patients, it is currently heavily used in this population. In fact, per evidence of barcode scanning via Meditech computer system at OU Medical Center 93% of the DNase prescribed in 2005 was for non Cystic fibrosis patients with an estimated yearly cost of $341,968.15.In vitro studies showed that the effect of Dnase was minimal on sputum viscosity when compared to Hypertonic saline . Furthermore recent studies on hypertonic saline in cystic fibrosis patients showed that it is an inexpensive and safe therapy when preceded by a bronchodilator in patients with cystic fibrosis.

We hereby propose a prospective randomized trial to compare the efficacy of hypertonic saline, DNase, vs. normal saline in the treatment of atelectasis in non cystic fibrosis, mechanically ventilated patient.

Study Overview

• Status: Completed
• Conditions: Atelectasis
• Intervention / Treatment: Drug: Normal saline:; Drug: Hypertonic Saline; Drug: Dornase alpha

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Presbyterian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient on invasive mechanical ventilation
2. New Onset (<48 hours) lobar or multilobar lung atelectasis based on CXR

Exclusion Criteria:

1. Asthma
2. Severe COPD (FEV1<30%)
3. Pneumothorax or massive pleural effusion, thought to be causing the atelectasis
4. Lobar atelectasis secondary to compressive tumor.
5. Severe hypoxemia (PaO2/FiO2 < 75)
6. Hemodynamic Instability
7. Cystic fibrosis patients
8. Allergy to DNase
9. Patients on Acetylcysteine
10. Pregnant women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Normal saline; Nebulized isotonic saline solution (4 ml of 0.9 % NaCl) twice daily, for a fixed period of 15 min, after a 15 min premedication with nebulized albuterol (2.5 mg diluted in 3 ml of 0.9 % NaCl).	Drug: Normal saline: Nebulized isotonic saline solution (4 ml of 0.9 % NaCl) twice daily, for a fixed period of 15 min, after a 15 min premedication with nebulized albuterol (2.5 mg diluted in 3 ml of 0.9 % NaCl).; Other Names: Normal Saline
Active Comparator: Hypertonic saline; Nebulized hypertonic saline solution (4 ml of 7 % NaCl) twice daily, for a fixed period of 15 min, after a 15 min premedication with nebulized albuterol (2.5 mg diluted in 3 ml of 0.9 % NaCl).	Drug: Hypertonic Saline; Nebulized hypertonic saline solution (4 ml of 7 % NaCl) twice daily, for a fixed period of 15 min, after a 15 min premedication with nebulized albuterol (2.5 mg diluted in 3 ml of 0.9 % NaCl).
Active Comparator: Dornase alpha; 2.5 mg of DNase (Dornase alpha, PULMOZYME® , Genentech, South San Francisco, CA), nebulized twice daily, after a 15 min premedication with nebulized albuterol (2.5 mg diluted in 3 ml of 0.9 % NaCl).	Drug: Dornase alpha; 2.5 mg of DNase (Dornase alpha, PULMOZYME® , Genentech, South San Francisco, CA), nebulized twice daily, after a 15 min premedication with nebulized albuterol (2.5 mg diluted in 3 ml of 0.9 % NaCl).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Chest X-ray Atelectasis Score	Each CXR was assigned an atelectasis score.(*) The absence or presence of contralateral hyperinflation was marked as 0 or 1 point, respectively. The absence or presence of mediastinal shift was scored as 0 or 1, respectively. Atelectasis was scored for each lobe. A partial atelectasis of one lobe was scored as one point, whereas complete atelectasis of a lobe was marked as two points. The distinction between infiltrate and atelectasis as well as the total scoring was done by the interpreting radiologist. These results were summed for each CXR. The score range from 0 to 10 with 0 indicates "no atelectasis",higher value indicates progressively more atelectasis. *Hendriks T, de Hoog M, Lequin MH, Devos AS, and Merkus PJ: DNase and atelectasis in non-cystic fibrosis pediatric patients. Crit Care. 2005;9:R351-R356.	Baseline(Day 0) to Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Extubation	percentage of patient who were extubated at day 7	7 days

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Investigators: Principal Investigator: Jean Keddissi, MD, University of Oklahoma

Publications and helpful links

General Publications

• Youness HA, Mathews K, Elya MK, Kinasewitz GT, Keddissi JI. Dornase alpha compared to hypertonic saline for lung atelectasis in critically ill patients. J Aerosol Med Pulm Drug Deliv. 2012 Dec;25(6):342-8. doi: 10.1089/jamp.2011.0954. Epub 2012 Mar 13.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: April 30, 2008
• First Submitted That Met QC Criteria: April 30, 2008
• First Posted (Estimate): May 5, 2008

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 1, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Atelectasis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pulmonary Atelectasis
• Other Study ID Numbers: 12783