Asthma
Conditions
Brief summary
This is a blinded observer randomized controlled trial comparing two nebulizer devices. The objective of this study is to evaluate the efficacy of two different nebulizers.
Detailed description
The investigators hypothesize that albuterol delivered with a breath-enhanced nebulizer will lead to statistically greater improvement in FEV1 when compared to an equivalent dose delivered via a standard t-piece nebulizer. The primary aim will be to study changes in forced expiratory volume in one second (FEV1) in patients presenting to an urban pediatric emergency department with a moderate to severe acute asthma exacerbation when utilizing these two nebulizers. Secondary aims will include evaluation of hospital admission rates, emergency department (ED) length of stay (LOS), changes in asthma severity scores, vital sign changes, medication side effects, and total quantity of albuterol given in the ED. A distal aim of the study will be to perform a cost analysis; though the investigators will likely need further clinical trials utilizing multiple dose administration in order to accurately analyze cost.
Interventions
DEVICET-Piece Nebulizer
Albuterol treatment administered with Hudson RCI® Micro Mist® nebulizer (Teleflex Medical®, Research Triangle Park, NJ)
DEVICEBreath-Enhanced Nebulizer
Albuterol treatment administered with NebuTech® HDN®, Breath-Enhanced High Density Jet Nebulizer (Salter Labs®, Arvin, CA)
DRUGAlbuterol
One time 5mg nebulized albuterol treatment given with one of two devices over 10 minutes.
PROCEDUREPre-Treatment Spirometry Measurement
Bedside spirometry measurements taken prior to albuterol therapy using ndd® EasyOne Plus® spirometer.
PROCEDUREPost-Treatment Spirometry Measurement
Bedside spirometry measurements taken after albuterol therapy using ndd® EasyOne Plus® spirometer.
Sponsors
University of Texas
Seton Healthcare Family
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 6 years and \< 18 years * History of physician diagnosed asthma * Presenting to ED with breathing difficulty or cough * Initial FEV1 25%-70% predicted * Parent or guardian speaks English or Spanish.
Exclusion criteria
* Pediatric Asthma Score of 0 * Pregnancy or breast-feeding * Immediate resuscitation required * Chronic lung disease (other than asthma) * Congenital heart disease * Neuromuscular disease * Suspected intrathoracic foreign body * Allergy or other contraindication to study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in FEV1 (% Predicted) | 10 minutes | Pre-treatment spirometry measurement assessed at the time of study enrollment. Post-treatment spirometry measurement assessed following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in FEV1 calculated as post-treatment FEV1 minus pre-treatment FEV1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in PASS Score (Points on a Scale) | 10 minutes | Determined by examination and auscultation of lungs to prior to and immediately following albuterol administration. PASS is a total score on a scale of 0-6 which is calculated as a sum of three sub-scores, each on a scale of 0-2. The sub-scores are: 1. Wheezing: None or Mild (0), Moderate (1), Severe wheezing or absent wheezing due to poor air exchange (2) 2. Work of breathing (accessory muscle use or retractions): None or mild (0), Moderate (1), Severe (2) 3. Prolonged expiration: Normal or mildly prolonged (0), moderately prolonged (1), severely prolonged (2) Pre-treatment assessment at the time of study enrollment. Post-treatment assessment following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in PASS calculated as post-treatment PASS minus pre-treatment PASS. |
| Percentage of Patients Requiring Inpatient Hospital Admission (% of Subjects) | Up to 24 hours | Admission rate to inpatient hospital will be assessed at the time of Emergency Department disposition which will be approximately 3 hours, but will be assessed up to 24 hours depending on duration of ED stay. |
| Emergency Department Length of Stay (Minutes) | Up to 24 hours | Total length of stay will be assessed at the time of Emergency Department disposition which will be approximately 3 hours, but will be assessed up to 24 hours depending on duration of ED stay. |
| Change in PAS Score (Points on a Scale) | 10 minutes | Based on examination and auscultation of lungs prior to and immediately following albuterol administration. PAS score is on a scale of 0-10 which is a sum of five separate sub-scores each on a scale of 0-2. The five sub-scores are: 1. Respiratory rate (6-12yr/\>12yr): \<=26/23 (0), 27-30/24-27 (1), \>31/28 (2) 2. Oxygenation: \>95% (0), 90-95 (1), \<90 (2) 3. Auscultation: clear/end expiratory wheeze (0), expiratory wheeze (1), biphasic wheeze/diminished (2) 4. Work of Breathing (accessory muscles): \<= 1 (0), 2 (1), \>=3 (2) 5. Dyspnea: Full sentences (0), Partial sentences (1), Single words (2) Pre-treatment assessment at the time of study enrollment. Post-treatment assessment following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in PAS calculated as post-treatment PAS minus pre-treatment PAS. |
| Total Quantity of Albuterol Given in the Emergency Department (mg) | up to 24 hours | Cumulative dose of albuterol in mg will be assessed at the time of Emergency Department disposition which will be approximately 3 hours, but will be assessed up to 24 hours depending on duration of ED stay. |
| Change Respiratory Rate (Breaths Per Minute) | 10 minutes | Respiratory rate will be measured by observation and auscultation over 30 seconds prior to and immediately following albuterol administration Pre-treatment assessment at the time of study enrollment. Post-treatment assessment following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in respiratory rate calculated as post-treatment respiratory rate minus pre-treatment respiratory rate. |
| Change in Heart Rate (Beats Per Minute) | 10 minutes | Blinded research personnel will assess subject's heart rate by auscultation and/or pulse palpation prior to and immediately following albuterol administration. Pre-treatment assessment at the time of study enrollment. Post-treatment assessment following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in heart rate calculated as post-treatment heart rate minus pre-treatment heart rate. |
| Percentage of Patients Experiencing Medication Side Effects (%) | 10 minutes | Subjects and parents/guardians will be asked whether subjects experienced nausea, vomiting, palpitations, headache, dizziness either during (assessed by non-blinded personnel) or following treatment (assessed by blinded personnel during post-treatment assessment). Subject and parent/guardian will also be asked if any other side effects were experienced. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| T-piece Nebulizer Pre-treatment spirometry measurement will be performed, intervention with a one time 5mg nebulized albuterol treatment will be administered with the experimental T-piece Nebulizer (Hudson RCI® Micro Mist® nebulizer Teleflex Medical®, Research Triangle Park, NJ). Treatment will be administered over 10 minutes. Following this therapy, post-treatment spirometry measurement will be performed.
T-Piece Nebulizer: Albuterol treatment administered with Hudson RCI® Micro Mist® nebulizer (Teleflex Medical®, Research Triangle Park, NJ)
Albuterol: One time 5mg nebulized albuterol treatment given with one of two devices over 10 minutes.
Pre-Treatment Spirometry Measurement: Bedside spirometry measurements taken prior to albuterol therapy using ndd® EasyOne Plus® spirometer.
Post-Treatment Spirometry Measurement: Bedside spirometry measurements taken after albuterol therapy using ndd® EasyOne Plus® spirometer. | 58 |
| Breath-Enhanced Nebulizer Pre-treatment spirometry measurement will be performed, intervention with a one time 5mg nebulized albuterol treatment will be administered with the experimental Breath-Enhanced Nebulizer (NebuTech® HDN®, Breath-Enhanced High Density Jet Nebulizer Salter Labs®, Arvin, CA). Treatment will be administered over 10 minutes. Following this therapy, post-treatment spirometry measurement will be performed.
Breath-Enhanced Nebulizer: Albuterol treatment administered with NebuTech® HDN®, Breath-Enhanced High Density Jet Nebulizer (Salter Labs®, Arvin, CA)
Albuterol: One time 5mg nebulized albuterol treatment given with one of two devices over 10 minutes.
Pre-Treatment Spirometry Measurement: Bedside spirometry measurements taken prior to albuterol therapy using ndd® EasyOne Plus® spirometer.
Post-Treatment Spirometry Measurement: Bedside spirometry measurements taken after albuterol therapy using ndd® EasyOne Plus® spirometer. | 57 |
| Total | 115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 1 |
Baseline characteristics
| Characteristic | T-piece Nebulizer | Total | Breath-Enhanced Nebulizer |
|---|---|---|---|
| Age, Continuous | 9.8 years STANDARD_DEVIATION 2.6 | 9.98 years STANDARD_DEVIATION 2.82 | 10.1 years STANDARD_DEVIATION 3 |
| Baseline Asthma Severity Mild Intermittent | 20 Participants | 47 Participants | 27 Participants |
| Baseline Asthma Severity Mild Persistent | 11 Participants | 23 Participants | 12 Participants |
| Baseline Asthma Severity Moderate Persistent | 20 Participants | 34 Participants | 14 Participants |
| Baseline Asthma Severity Severe Persistent | 7 Participants | 11 Participants | 4 Participants |
| Duration of symptoms (days) | 2 days | 2 days | 2 days |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants | 63 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 52 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Initial FEV1 (% predicted) | 39.4 %predicted STANDARD_DEVIATION 13.4 | 40.5 %predicted STANDARD_DEVIATION 14.4 | 42 %predicted STANDARD_DEVIATION 14.8 |
| Initial O2 | 96.0 %saturation STANDARD_DEVIATION 2.1 | 95.8 %saturation STANDARD_DEVIATION 2.4 | 95.7 %saturation STANDARD_DEVIATION 2.6 |
| Initial PAS score | 4 units on a scale | 4 units on a scale | 4 units on a scale |
| Initial PASS score | 2 units on a scale | 2 units on a scale | 2 units on a scale |
| Initial RR (bpm) | 28.1 breaths/min STANDARD_DEVIATION 9.4 | 28.4 breaths/min STANDARD_DEVIATION 8.5 | 28.9 breaths/min STANDARD_DEVIATION 7.6 |
| Region of Enrollment United States | 58 participants | 115 participants | 57 participants |
| Sex: Female, Male Female | 21 Participants | 51 Participants | 30 Participants |
| Sex: Female, Male Male | 37 Participants | 64 Participants | 27 Participants |
| Weight (kg) | 39.5 kilograms STANDARD_DEVIATION 16.4 | 40.7 kilograms STANDARD_DEVIATION 16.5 | 41.1 kilograms STANDARD_DEVIATION 16.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 57 |
| other Total, other adverse events | 5 / 58 | 5 / 57 |
| serious Total, serious adverse events | 0 / 58 | 0 / 57 |
Outcome results
Primary
Change in FEV1 (% Predicted)
Pre-treatment spirometry measurement assessed at the time of study enrollment. Post-treatment spirometry measurement assessed following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in FEV1 calculated as post-treatment FEV1 minus pre-treatment FEV1
Time frame: 10 minutes
Population: Eight subjects unable to complete post-treatment spirometry (three in T-piece group, five in breath-enhanced group)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| T-piece Nebulizer | Change in FEV1 (% Predicted) | 13.8 %predicted |
| Breath-Enhanced Nebulizer | Change in FEV1 (% Predicted) | 9.1 %predicted |
p-value: 0.04t-test, 2 sided
Secondary
Change in Heart Rate (Beats Per Minute)
Blinded research personnel will assess subject's heart rate by auscultation and/or pulse palpation prior to and immediately following albuterol administration. Pre-treatment assessment at the time of study enrollment. Post-treatment assessment following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in heart rate calculated as post-treatment heart rate minus pre-treatment heart rate.
Time frame: 10 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| T-piece Nebulizer | Change in Heart Rate (Beats Per Minute) | 4.34 beats per minute |
| Breath-Enhanced Nebulizer | Change in Heart Rate (Beats Per Minute) | 15.05 beats per minute |
Secondary
Change in PAS Score (Points on a Scale)
Based on examination and auscultation of lungs prior to and immediately following albuterol administration. PAS score is on a scale of 0-10 which is a sum of five separate sub-scores each on a scale of 0-2. The five sub-scores are: 1. Respiratory rate (6-12yr/\>12yr): \<=26/23 (0), 27-30/24-27 (1), \>31/28 (2) 2. Oxygenation: \>95% (0), 90-95 (1), \<90 (2) 3. Auscultation: clear/end expiratory wheeze (0), expiratory wheeze (1), biphasic wheeze/diminished (2) 4. Work of Breathing (accessory muscles): \<= 1 (0), 2 (1), \>=3 (2) 5. Dyspnea: Full sentences (0), Partial sentences (1), Single words (2) Pre-treatment assessment at the time of study enrollment. Post-treatment assessment following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in PAS calculated as post-treatment PAS minus pre-treatment PAS.
Time frame: 10 minutes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| T-piece Nebulizer | Change in PAS Score (Points on a Scale) | -1 score on a scale |
| Breath-Enhanced Nebulizer | Change in PAS Score (Points on a Scale) | -2 score on a scale |
p-value: 0.29Wilcoxon (Mann-Whitney)
Secondary
Change in PASS Score (Points on a Scale)
Determined by examination and auscultation of lungs to prior to and immediately following albuterol administration. PASS is a total score on a scale of 0-6 which is calculated as a sum of three sub-scores, each on a scale of 0-2. The sub-scores are: 1. Wheezing: None or Mild (0), Moderate (1), Severe wheezing or absent wheezing due to poor air exchange (2) 2. Work of breathing (accessory muscle use or retractions): None or mild (0), Moderate (1), Severe (2) 3. Prolonged expiration: Normal or mildly prolonged (0), moderately prolonged (1), severely prolonged (2) Pre-treatment assessment at the time of study enrollment. Post-treatment assessment following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in PASS calculated as post-treatment PASS minus pre-treatment PASS.
Time frame: 10 minutes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| T-piece Nebulizer | Change in PASS Score (Points on a Scale) | -1 score on a scale |
| Breath-Enhanced Nebulizer | Change in PASS Score (Points on a Scale) | -1 score on a scale |
p-value: 0.97Wilcoxon (Mann-Whitney)
Secondary
Change Respiratory Rate (Breaths Per Minute)
Respiratory rate will be measured by observation and auscultation over 30 seconds prior to and immediately following albuterol administration Pre-treatment assessment at the time of study enrollment. Post-treatment assessment following the administration of one time 5mg nebulized albuterol sulfate treatment. Assessments taken at baseline (prior to albuterol therapy) and 10 min post-treatment. Change in respiratory rate calculated as post-treatment respiratory rate minus pre-treatment respiratory rate.
Time frame: 10 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| T-piece Nebulizer | Change Respiratory Rate (Breaths Per Minute) | -3.1 breaths/min |
| Breath-Enhanced Nebulizer | Change Respiratory Rate (Breaths Per Minute) | -3.2 breaths/min |
Secondary
Emergency Department Length of Stay (Minutes)
Total length of stay will be assessed at the time of Emergency Department disposition which will be approximately 3 hours, but will be assessed up to 24 hours depending on duration of ED stay.
Time frame: Up to 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| T-piece Nebulizer | Emergency Department Length of Stay (Minutes) | 246.3 minutes |
| Breath-Enhanced Nebulizer | Emergency Department Length of Stay (Minutes) | 246.2 minutes |
p-value: 0.99t-test, 2 sided
Secondary
Percentage of Patients Experiencing Medication Side Effects (%)
Subjects and parents/guardians will be asked whether subjects experienced nausea, vomiting, palpitations, headache, dizziness either during (assessed by non-blinded personnel) or following treatment (assessed by blinded personnel during post-treatment assessment). Subject and parent/guardian will also be asked if any other side effects were experienced.
Time frame: 10 minutes
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| T-piece Nebulizer | Percentage of Patients Experiencing Medication Side Effects (%) | 5 Participants |
| Breath-Enhanced Nebulizer | Percentage of Patients Experiencing Medication Side Effects (%) | 5 Participants |
p-value: 1Fisher Exact
Secondary
Percentage of Patients Requiring Inpatient Hospital Admission (% of Subjects)
Admission rate to inpatient hospital will be assessed at the time of Emergency Department disposition which will be approximately 3 hours, but will be assessed up to 24 hours depending on duration of ED stay.
Time frame: Up to 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| T-piece Nebulizer | Percentage of Patients Requiring Inpatient Hospital Admission (% of Subjects) | 11 Participants |
| Breath-Enhanced Nebulizer | Percentage of Patients Requiring Inpatient Hospital Admission (% of Subjects) | 11 Participants |
p-value: 0.96Chi-squared
Secondary
Total Quantity of Albuterol Given in the Emergency Department (mg)
Cumulative dose of albuterol in mg will be assessed at the time of Emergency Department disposition which will be approximately 3 hours, but will be assessed up to 24 hours depending on duration of ED stay.
Time frame: up to 24 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| T-piece Nebulizer | Total Quantity of Albuterol Given in the Emergency Department (mg) | 18.2 mg |
| Breath-Enhanced Nebulizer | Total Quantity of Albuterol Given in the Emergency Department (mg) | 18.7 mg |