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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Lung Injury; Adult Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Nebulized hypertonic saline

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in the respiratory parameters	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.	baseline and every 6 hours for 36 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death within 28 days	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.	28 days or discharge
lung dysfunction scores	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.	baseline and 28 days or discharge
ventilator-free days (VFD)	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.	baseline and 28 days or discharge
MOF scores (Denver MOF score)	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	28 days or discharge

Collaborators and Investigators

• Sponsor: Denver Health and Hospital Authority
• Collaborators: University of Colorado, Denver
• Investigators: Principal Investigator: Ernest E Moore, MD, Denver Health and Hospital Authority

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2012
• Primary Completion (ACTUAL): November 6, 2018
• Study Completion (ACTUAL): November 6, 2018

Study Registration Dates

• First Submitted: August 10, 2012
• First Submitted That Met QC Criteria: August 16, 2012
• First Posted (ESTIMATE): August 17, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 8, 2019
• Last Update Submitted That Met QC Criteria: January 4, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: trauma; acute lung injury; adult respiratory distress syndrome
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Wounds and Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: COMIRB #11-0706