Clinical trial NCT02966184
Conditions: Status Asthmaticus
Sponsor: Norton Healthcare
Start date: 2018-09-10; Completion date: 2018-10-25
Enrollment: 8 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is designed to compare the length of continuous albuterol administration between two different albuterol formulations, BAC containing albuterol versus preservative free albuterol.

Detailed description:
The primary objective of this study is to compare the length of continuous albuterol administration between patients receiving BAC containing albuterol versus preservative free albuterol. Secondary objectives include comparison of therapy escalation, asthma scores, forced expiratory volume in one second (FEV1) at discharge, length of hospital stay, and cost.

Arms: arm 1: This arm includes the current standard of care which patients receive at the institution. No interventions will be made within this group of patients. arm 2: This arm includes the preservative free albuterol which is being investigated. Treatment for this arm will follow current standards of care, with the only difference being the albuterol formulation.
Interventions: intervention 1: preservative free albuterol
Intervention descriptions: intervention 1: Preservative free albuterol for nebulization

Protocol documents:
Prot_SAP_000.pdf: 
Version Date: 07/18/18
COMPARISON OF BENZALKONIUM CHLORIDE 
CONTAINING ALBUTEROL VERSUS PRESERVATIVE 
FREE ALBUTEROL FOR THE TREATMENT OF 
STATUS ASTHMATICUS
BACKGROUND
In 2014, the Centers for Disease Control and Prevention reported approximately 6.3 million children in 
the United States with a diagnosis of asthma.1 According  to the National Heart, Lung, and Blood 
Institute, inpatient management of an acute asthma exacerbation may include continuous albuterol 
administration.2 Due to higher dosing requirements over an extended duration of time, continuous 
albuterol administration requires a larger volume of albuterol solution, which is often obtained from a 
multi-dose vial containing benzalkonium chloride (BAC). BAC is a common preservative used in 
pharmaceuticals, but also considered to be a potent bronchoconstrictor. BAC doses as low as 124 
micrograms have been shown to cause bronchoconstriction. This effect is cumulative, prolonged, and 
correlates directly with basal airway responsiveness.3 The multi-dose albuterol vials currently used for 
continuous albuterol administration contain 50 micrograms of BAC per 2.5 milligrams of albuterol. A 
patient receiving continuous albuterol inhalation at 20 milligrams per hour will receive 400 micrograms 
of BAC per hour. In the 1999 study conducted by Asmus et al., the mean concentration of BAC required 
to provoke a 20% drop in FEV1 was 300 micrograms (range 124 to 1947 micrograms).4 This raises 
concern that the bronchoconstricting effects of BAC may antagonize the therapeutic goals of albuterol 
therapy among patients receiving continuous albuterol inhalation for extended periods of time.
OBJECTIVE
The primary objective of this study is to compare the length of continuous albuterol administration 
between patients receiving BAC-containing albuterol (BAC-albuterol) versus preservative free albuterol 
(PF-albuterol). Secondary objectives include comparison of therapy escalation, asthma scores, forced 
expiratory volume in one second (FEV1) at discharge, length of hospital stay, and cost. 
METHODS
A prospective, patient-blinded, randomized study will be conducted comparing patients admitted to 
Norton Children’s Hospital for an asthma exacerbation. There will be no active recruitment of patients; 
however, eligible patients will be those who present to our emergency department in status 
asthmaticus. Patients will be randomly assigned to a patient room on 5 West versus 5 East upon 
admission based on bed availability. The Pyxis on 5 West will contain the standard multi-dose albuterol 
vial which contains BAC (current standard of care), while pharmacy will be preparing and dispensing PF-
albuterol to patients on 5 East who are enrolled in the study. The treatment of patients will not vary 
between groups, nor deviate from the standard of care currently implemented at the institution. If a 
patient consents to study enrollment, he/she will receive PF-albuterol while awaiting bed assignment in 
the emergency department. This is essential to avoid confounding the results of the study, as BAC has a 
UofL Institutional Review Boards
IRB NUMBER: 16.0721


Version Date: 07/18/18
prolonged half-life and may have clinical consequences even after a patient is randomized to receive 
PF-albuterol. 
Informed consent will be required for all patients, and assent will additionally be required for patients 
between 7 and 17 years of age. The study will be explained by a study investigator or respiratory 
therapist (under the supervision of the respiratory therapy director) and informed consent/assent 
paperwork will be provided to the patient/caregiver while in the emergency department. 
Approximately 10-20 minutes will be allotted for the consent/assent process. The difference between 
groups is the formulation of albuterol being used, and both formulations have FDA approval for use in 
status asthmaticus.
INCLUSION AND EXCLUSION CRITERIA 
Patients will be included in the study if they are admitted to the 5th floor at Norton Children’s Hospital 
for the treatment of an acute asthma exacerbation, initiated on continuous albuterol inhalation therapy, 
and are between 3 and 17 years of age. 
Patients will be excluded from the study if they are transferred to the 5th floor from any other unit 
except the emergency department, admitted for any indication other than acute asthma exacerbation, 
or exposed to BAC prior to admission.
DATA COLLECTION
Demographic information collected will include age, gender, weight, and ethnicity.
Data gathered pertaining to continuous albuterol administration will include albuterol formulation, 
dose, length of therapy, cost of medication administered, and amount of BAC administered. 
Additional parameters obtained will include admission asthma score, escalation of therapy related to 
asthma exacerbation, time on supplemental oxygen, transfer to higher acuity care, total hospital length 
of stay, and discharge FEV1.
A data collection document will be used by the respiratory therapist to collect start/stop time of 
continuous albuterol, evidence of patient non-adherence, and re-initiation of continuous albuterol. 
After completion, this document will be stored in a binder, in a cabinet, within a locked office. All data 
(from the data collection form and from the electronic medical record) collected will be stored in an 
Excel spreadsheet for data analysis. The data collection sheet to be used is attached. Data collected will 
be stored on a password protected computer, within a locked office, and will be restricted to the 
primary investigator. All information will be de-identified once entered into the data collection sheet.
STATISCIAL ANALYSIS
A power analysis will be conducted in order to determine the sample size needed to detect a statistical 
difference between groups. Descriptive statistics will be used to evaluate population demographics, 
while comparison data will be analyzed using a two-tailed student t-test. 
UofL Institutional Review Boards
IRB NUMBER: 16.0721


Version Date: 07/18/18
CITATIONS
1.
National Center for Health Statistics. Asthma, United States, 2014: Morbidity: Children (under 
age 18 years). Hyattsville, Maryland. 2014 
2.
Guidelines for the Diagnosis and Management of Asthma (EPR-3). NHLBI, NIH. National 
Institutes of Health, July 2007
3.
Zhang YG, Wright WJ, Tam WK, Nguyen-Dang TH, Salome CL, Woolcock AJ. Effect of Inhaled 
Preservatives on Asthmatic Subjects: II. Benzalkonium Chloride.  Am Rev Respir Dis American 
Review of Respiratory Disease 141.6 : 1405-408. 1990
4.
Asmus MJ, Sherman J, Hendeles L. Bronchoconstrictor additives in bronchodilator solutions. J 
Allergy Clin Immunol 104:S53-S6. 1999
UofL Institutional Review Boards
IRB NUMBER: 16.0721