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

Study Overview
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Brief Summary
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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.

Official Title
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Dornase Alpha Versus Hypertonic Saline for Lung Atelectasis

Conditions
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Atelectasis

Intervention / Treatment
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* Drug: Normal saline:
* Drug: Hypertonic Saline
* Drug: Dornase alpha


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient on invasive mechanical ventilation New Onset (<48 hours) lobar or multilobar lung atelectasis based on CXR Exclusion Criteria: Asthma Severe COPD (FEV1<30%) Pneumothorax or massive pleural effusion, thought to be causing the atelectasis Lobar atelectasis secondary to compressive tumor. Severe hypoxemia (PaO2/FiO2 < 75) Hemodynamic Instability Cystic fibrosis patients Allergy to DNase Patients on Acetylcysteine Pregnant women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

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 |
| --- | --- |
| Placebo Comparator: Normal saline<br>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:<br>* 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).<br>* Other names: Normal Saline;|
| Active Comparator: Hypertonic saline<br>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<br>* 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).<br>|
| Active Comparator: Dornase alpha<br>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<br>* 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).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atelectasis