Clinical Trial of Nebulized Hypertonic Saline to Attenuate Post-Traumatic Acute Lung Injury

Sponsor

Denver Health and Hospital Authority (Other)

Overall Status

Terminated

CT.gov ID

NCT01667666

Collaborator

University of Colorado, Denver (Other)

Enrollment

Location

Arm

78.2

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates the use of nebulized hypertonic saline (aerosolized salt water) as a preventive treatment for post-traumatic acute lung injury (ALI). Both animal and human research indicate that aerosolized salt water might help reduce harmful inflammation with minimal risks.

Condition or Disease	Intervention/Treatment	Phase
Acute Lung Injury Adult Respiratory Distress Syndrome	Drug: Nebulized hypertonic saline	Phase 1

Detailed Description

Despite over 40 years of investigation, acute lung injury (ALI) remains a leading cause of morbidity in critically ill patients, and a disease for which there is no effective pharmacologic therapy. Our group and others have focused on the anti-inflammatory effects of intravenous hypertonic saline (HTS) acting on the injured endothelium with promising results experimentally, but failed to confirm the benefit clinically. Recent work, however, has shown that inhaled or nebulized HTS targeted at the epithelium is safe and effective in treating cystic fibrosis, COPD, and neonatal bronchiolitis. Recognizing the central role of the pulmonary epithelium in ALI, nebulization has the advantage of achieving high concentrations of the therapy without producing systemic side effects. Thus, we hypothesize that nebulized hypertonic saline will attenuate acute lung injury following trauma.

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Clinical Study to Determine if Nebulized Hypertonic Saline Attenuates Acute Lung Injury Following Trauma and Hemorrhagic Shock

Actual Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Nov 6, 2018

Actual Study Completion Date :

Nov 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nebulized HTS The first 5 patients will receive 3% Nebulized hypertonic saline, the second 5 patients will receive 4.5% Nebulized hypertonic saline, the third group 6% Nebulized hypertonic saline, and the fourth group of 5 patients will receive 7% Nebulized hypertonic saline. The nebulizer is dosed 2-3 times a day for 36 hours.	Drug: Nebulized hypertonic saline The first 5 patients will receive 3% hypertonic saline in a nebulizer, the second 5 patients will receive 4.5% nebulized hypertonic saline, the third group 6% nebulized hypertonic saline, and the fourth group of 5 patients will receive 7% nebulized hypertonic saline. The nebulizer is dosed 2-3 times a day for 36 hours.

Arm

Intervention/Treatment

Experimental: Nebulized HTS

The first 5 patients will receive 3% Nebulized hypertonic saline, the second 5 patients will receive 4.5% Nebulized hypertonic saline, the third group 6% Nebulized hypertonic saline, and the fourth group of 5 patients will receive 7% Nebulized hypertonic saline. The nebulizer is dosed 2-3 times a day for 36 hours.

Drug: Nebulized hypertonic saline

The first 5 patients will receive 3% hypertonic saline in a nebulizer, the second 5 patients will receive 4.5% nebulized hypertonic saline, the third group 6% nebulized hypertonic saline, and the fourth group of 5 patients will receive 7% nebulized hypertonic saline. The nebulizer is dosed 2-3 times a day for 36 hours.

Outcome Measures

Primary Outcome Measures

change in the respiratory parameters [baseline and every 6 hours for 36 hours]
For intubated patients - A decrease greater than 20% in PaO2/FiO2 (P/F) ratios will trigger DSMB review. For not intubated patients - a) the need to increase FiO2 by 10% (approximate 4 liter/minute increase) to maintain a peripheral oxygen saturation (SaO2) of 90% during nebulizer treatment; b) evidence of respiratory distress (as documented in the chart by the patient's attending) during nebulizer treatment; and c) respiratory insufficiency requiring intubation and mechanical ventilation at any point will trigger DSMB review.

Secondary Outcome Measures

death within 28 days [28 days or discharge]
If the rate of death within 28 days for this patient population is less than 50% the expected rate for every 5 patients based on our clinical trauma database over the past 5 years, a DSMB review will be triggered.
lung dysfunction scores [baseline and 28 days or discharge]
Denver lung MOF score will be measure daily until discharge or 28 days, which ever is first. For every 5 patients, if the rate of lung dysfunction for this patient population is less than 50% the expected rate based on our clinical trauma database over the past 5 years, a DSMB review will be triggered.
ventilator-free days (VFD) [baseline and 28 days or discharge]
Ventilator free days will be tracked with 28 days as a reference. If the number of VFDs for this patient population is greater than one standard deviation of the predicted value for every 5 patients based on our clinical trauma database over the past 5 years, a DSMB review will be triggered.
MOF scores (Denver MOF score) [28 days or discharge]
Denver MOF score will be recorded daily until discharge or 28 days, which ever is sooner. for every 5 patients, if the rate of MOF for this patient population is greater than one standard deviation of the predicted value for every 5 patients based on our clinical trauma database over the past 5 years, a DSMB review will be triggered

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

adult 18 ≤ age ≤ 65
trauma with a 9 ≤ NISS ≤ 36
≤10 units of RBC in the first 6 hours (as this is a major risk factor for ARDS and MOF in this population)

Exclusion Criteria:

Direct or indirect lung injury
Elevated intracranial pressure requiring treatment, including but not limited to mannitol, intravenous hypertonic saline, and ventricular drainage
History of severe chronic respiratory disease
Child-Pugh Class C liver failure
Prisoners
Pregnant women