Trial Outcomes & Findings for A Randomized Trial Comparing Metered Dose Inhalers and Breath Actuated Nebulizers (NCT NCT02777125)

Results Overview

Patient disposition is measured as subjects requiring further treatment and being admitted to hospital. We record the number of patients in each cohort that required admission to the hospital after being evaluated and treated in the Emergency Department.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

980 participants

Primary outcome timeframe

6 hours

Results posted on

2017-08-15

Participant Flow

Participant milestones

Participant milestones
Measure	Albuterol by Metered Dose Inhaler Albuterol administered via MDI and spacer device with weight and severity based dosing. For weight less than 20 kg: mild and moderate disease 540mcg of albuterol per dose. For weight greater than or equal to 20 kg: mild disease 540 mcg of albuterol per dose and moderate disease 1080 mcg of albuterol per dose. Metered Dose Inhaler: A metered dose inhaler (MDI) is a small hand held pressurized canister device that contains both a medication, in this case albuterol, and a propellant. Pressing the device delivers 90mcg of albuterol. The MDI is attached to a spacer device, which is a one way holding chamber which allows the medication to be delivered over a series of breaths.	Albuterol Breath Actuated Nebulizer Subjects randomized to BAN were evaluated for proper breath actuation technique. The device settings were changed to provide continuous nebulization with a facemask if the patient could not breath actuate. Children presenting in the mild and moderate severity category weighing less than 20kg, received 2500mcg of albuterol. Children weighing more than 20kg, received 2500mcg of albuterol if their presentation met mild severity criteria, or 5000mcg if they met moderate criteria. Breath Actuated Nebulizer: The breath actuated nebulizer (BAN) device is a device that converts liquid medication, into an aerosol. It consists of a mouthpiece, a medication reservoir, and connective tubing that attaches to a compressor. This BAN device delivers medication when the patient takes a breath, but it can be attached to a mask and set to continuous nebulization for patients that are not able to coordinate their breaths.
Overall Study STARTED	488	492
Overall Study COMPLETED	445	445
Overall Study NOT COMPLETED	43	47

Reasons for withdrawal

Reasons for withdrawal
Measure	Albuterol by Metered Dose Inhaler Albuterol administered via MDI and spacer device with weight and severity based dosing. For weight less than 20 kg: mild and moderate disease 540mcg of albuterol per dose. For weight greater than or equal to 20 kg: mild disease 540 mcg of albuterol per dose and moderate disease 1080 mcg of albuterol per dose. Metered Dose Inhaler: A metered dose inhaler (MDI) is a small hand held pressurized canister device that contains both a medication, in this case albuterol, and a propellant. Pressing the device delivers 90mcg of albuterol. The MDI is attached to a spacer device, which is a one way holding chamber which allows the medication to be delivered over a series of breaths.	Albuterol Breath Actuated Nebulizer Subjects randomized to BAN were evaluated for proper breath actuation technique. The device settings were changed to provide continuous nebulization with a facemask if the patient could not breath actuate. Children presenting in the mild and moderate severity category weighing less than 20kg, received 2500mcg of albuterol. Children weighing more than 20kg, received 2500mcg of albuterol if their presentation met mild severity criteria, or 5000mcg if they met moderate criteria. Breath Actuated Nebulizer: The breath actuated nebulizer (BAN) device is a device that converts liquid medication, into an aerosol. It consists of a mouthpiece, a medication reservoir, and connective tubing that attaches to a compressor. This BAN device delivers medication when the patient takes a breath, but it can be attached to a mask and set to continuous nebulization for patients that are not able to coordinate their breaths.
Overall Study Consent form violation	14	12
Overall Study Assent form violation	21	23
Overall Study Protocol Violation	8	12

Baseline Characteristics

A Randomized Trial Comparing Metered Dose Inhalers and Breath Actuated Nebulizers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Albuterol by Metered Dose Inhaler n=445 Participants Albuterol administered via MDI and spacer device with weight and severity based dosing. For weight less than 20 kg: mild and moderate disease 540mcg of albuterol per dose. For weight greater than or equal to 20 kg: mild disease 540 mcg of albuterol per dose and moderate disease 1080 mcg of albuterol per dose. Metered Dose Inhaler: A metered dose inhaler (MDI) is a small hand held pressurized canister device that contains both a medication, in this case albuterol, and a propellant. Pressing the device delivers 90mcg of albuterol. The MDI is attached to a spacer device, which is a one way holding chamber which allows the medication to be delivered over a series of breaths.	Albuterol Breath Actuated Nebulizer n=445 Participants Subjects randomized to BAN were evaluated for proper breath actuation technique. The device settings were changed to provide continuous nebulization with a facemask if the patient could not breath actuate. Children presenting in the mild and moderate severity category weighing less than 20kg, received 2500mcg of albuterol. Children weighing more than 20kg, received 2500mcg of albuterol if their presentation met mild severity criteria, or 5000mcg if they met moderate criteria. Breath Actuated Nebulizer: The breath actuated nebulizer (BAN) device is a device that converts liquid medication, into an aerosol. It consists of a mouthpiece, a medication reservoir, and connective tubing that attaches to a compressor. This BAN device delivers medication when the patient takes a breath, but it can be attached to a mask and set to continuous nebulization for patients that are not able to coordinate their breaths.	Total n=890 Participants Total of all reporting groups
Age, Categorical <=18 years	445 Participants n=5 Participants	445 Participants n=7 Participants	890 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	6.37 years STANDARD_DEVIATION 3.9 • n=5 Participants	6.38 years STANDARD_DEVIATION 4.0 • n=7 Participants	6.37 years STANDARD_DEVIATION 3.93 • n=5 Participants
Sex: Female, Male Female	166 Participants n=5 Participants	147 Participants n=7 Participants	313 Participants n=5 Participants
Sex: Female, Male Male	279 Participants n=5 Participants	298 Participants n=7 Participants	577 Participants n=5 Participants
Region of Enrollment United States	445 participants n=5 Participants	445 participants n=7 Participants	890 participants n=5 Participants
Pediatric Asthma Score at Presentation	7.7 units on a scale STANDARD_DEVIATION 1.7 • n=5 Participants	8.0 units on a scale STANDARD_DEVIATION 1.6 • n=7 Participants	7.9 units on a scale STANDARD_DEVIATION 1.6 • n=5 Participants

PRIMARY outcome

Timeframe: 6 hours

Patient disposition is measured as subjects requiring further treatment and being admitted to hospital. We record the number of patients in each cohort that required admission to the hospital after being evaluated and treated in the Emergency Department.

Outcome measures

Outcome measures
Measure	Albuterol by Metered Dose Inhaler n=445 Participants Albuterol administered via MDI and spacer device with weight and severity based dosing. For weight less than 20 kg: mild and moderate disease 540mcg of albuterol per dose. For weight greater than or equal to 20 kg: mild disease 540 mcg of albuterol per dose and moderate disease 1080 mcg of albuterol per dose. Metered Dose Inhaler: A metered dose inhaler (MDI) is a small hand held pressurized canister device that contains both a medication, in this case albuterol, and a propellant. Pressing the device delivers 90mcg of albuterol. The MDI is attached to a spacer device, which is a one way holding chamber which allows the medication to be delivered over a series of breaths.	Albuterol Breath Actuated Nebulizer n=445 Participants Subjects randomized to BAN were evaluated for proper breath actuation technique. The device settings were changed to provide continuous nebulization with a facemask if the patient could not breath actuate. Children presenting in the mild and moderate severity category weighing less than 20kg, received 2500mcg of albuterol. Children weighing more than 20kg, received 2500mcg of albuterol if their presentation met mild severity criteria, or 5000mcg if they met moderate criteria. Breath Actuated Nebulizer: The breath actuated nebulizer (BAN) device is a device that converts liquid medication, into an aerosol. It consists of a mouthpiece, a medication reservoir, and connective tubing that attaches to a compressor. This BAN device delivers medication when the patient takes a breath, but it can be attached to a mask and set to continuous nebulization for patients that are not able to coordinate their breaths.
Number of Participant's Admitted to the Hospital for Further Treatment	53 Participants admitted to the Hospital	57 Participants admitted to the Hospital

SECONDARY outcome

Timeframe: 6 hours

Emergency department length of stay is defined as the point of time when the patient checked into the Emergency Department to the time of final disposition.

Outcome measures

Outcome measures
Measure	Albuterol by Metered Dose Inhaler n=445 Participants Albuterol administered via MDI and spacer device with weight and severity based dosing. For weight less than 20 kg: mild and moderate disease 540mcg of albuterol per dose. For weight greater than or equal to 20 kg: mild disease 540 mcg of albuterol per dose and moderate disease 1080 mcg of albuterol per dose. Metered Dose Inhaler: A metered dose inhaler (MDI) is a small hand held pressurized canister device that contains both a medication, in this case albuterol, and a propellant. Pressing the device delivers 90mcg of albuterol. The MDI is attached to a spacer device, which is a one way holding chamber which allows the medication to be delivered over a series of breaths.	Albuterol Breath Actuated Nebulizer n=445 Participants Subjects randomized to BAN were evaluated for proper breath actuation technique. The device settings were changed to provide continuous nebulization with a facemask if the patient could not breath actuate. Children presenting in the mild and moderate severity category weighing less than 20kg, received 2500mcg of albuterol. Children weighing more than 20kg, received 2500mcg of albuterol if their presentation met mild severity criteria, or 5000mcg if they met moderate criteria. Breath Actuated Nebulizer: The breath actuated nebulizer (BAN) device is a device that converts liquid medication, into an aerosol. It consists of a mouthpiece, a medication reservoir, and connective tubing that attaches to a compressor. This BAN device delivers medication when the patient takes a breath, but it can be attached to a mask and set to continuous nebulization for patients that are not able to coordinate their breaths.
Emergency Department Length of Stay Mild severity	192 minutes Standard Deviation 96	197 minutes Standard Deviation 90
Emergency Department Length of Stay Moderate severity	232 minutes Standard Deviation 125	245 minutes Standard Deviation 98

SECONDARY outcome

Timeframe: 6 hours

Defined as anytime after initiation of therapy when the patient's heart rate exceeded age adjusted normal sinus rhythm heart rates for their age. Not uncommonly, patient's experience tachycardia as an unintended side effect of receiving albuterol. Tachycardia can result in a patient requiring further observation in the Emergency department and therefore increasing Emergency Department length of stay. We want to determine if indeed tachycardia is unavoidable, or if its presence suggests that patients are receiving too much albuterol or if albuterol is being given by the wrong appliance.

Outcome measures

Outcome measures
Measure	Albuterol by Metered Dose Inhaler n=445 Participants Albuterol administered via MDI and spacer device with weight and severity based dosing. For weight less than 20 kg: mild and moderate disease 540mcg of albuterol per dose. For weight greater than or equal to 20 kg: mild disease 540 mcg of albuterol per dose and moderate disease 1080 mcg of albuterol per dose. Metered Dose Inhaler: A metered dose inhaler (MDI) is a small hand held pressurized canister device that contains both a medication, in this case albuterol, and a propellant. Pressing the device delivers 90mcg of albuterol. The MDI is attached to a spacer device, which is a one way holding chamber which allows the medication to be delivered over a series of breaths.	Albuterol Breath Actuated Nebulizer n=445 Participants Subjects randomized to BAN were evaluated for proper breath actuation technique. The device settings were changed to provide continuous nebulization with a facemask if the patient could not breath actuate. Children presenting in the mild and moderate severity category weighing less than 20kg, received 2500mcg of albuterol. Children weighing more than 20kg, received 2500mcg of albuterol if their presentation met mild severity criteria, or 5000mcg if they met moderate criteria. Breath Actuated Nebulizer: The breath actuated nebulizer (BAN) device is a device that converts liquid medication, into an aerosol. It consists of a mouthpiece, a medication reservoir, and connective tubing that attaches to a compressor. This BAN device delivers medication when the patient takes a breath, but it can be attached to a mask and set to continuous nebulization for patients that are not able to coordinate their breaths.
Number of Patients With Tachycardia After Treatment	101 Participants	141 Participants

SECONDARY outcome

Timeframe: 6 hours

Defined as a patient needing ondansetron for symptomatic relief of their nausea after initiating therapy in the Emergency Department.

Outcome measures

Outcome measures
Measure	Albuterol by Metered Dose Inhaler n=445 Participants Albuterol administered via MDI and spacer device with weight and severity based dosing. For weight less than 20 kg: mild and moderate disease 540mcg of albuterol per dose. For weight greater than or equal to 20 kg: mild disease 540 mcg of albuterol per dose and moderate disease 1080 mcg of albuterol per dose. Metered Dose Inhaler: A metered dose inhaler (MDI) is a small hand held pressurized canister device that contains both a medication, in this case albuterol, and a propellant. Pressing the device delivers 90mcg of albuterol. The MDI is attached to a spacer device, which is a one way holding chamber which allows the medication to be delivered over a series of breaths.	Albuterol Breath Actuated Nebulizer n=445 Participants Subjects randomized to BAN were evaluated for proper breath actuation technique. The device settings were changed to provide continuous nebulization with a facemask if the patient could not breath actuate. Children presenting in the mild and moderate severity category weighing less than 20kg, received 2500mcg of albuterol. Children weighing more than 20kg, received 2500mcg of albuterol if their presentation met mild severity criteria, or 5000mcg if they met moderate criteria. Breath Actuated Nebulizer: The breath actuated nebulizer (BAN) device is a device that converts liquid medication, into an aerosol. It consists of a mouthpiece, a medication reservoir, and connective tubing that attaches to a compressor. This BAN device delivers medication when the patient takes a breath, but it can be attached to a mask and set to continuous nebulization for patients that are not able to coordinate their breaths.
Number of Patients Requiring Ondansetron Dosing	14 Participants	18 Participants

SECONDARY outcome

Timeframe: Within 7 days of initial presentation

Defined as a repeat visit to the Emergency Department for a complaint related to their wheezing, within 7 days of initial enrollment in the study.

Outcome measures

Outcome measures
Measure	Albuterol by Metered Dose Inhaler n=445 Participants Albuterol administered via MDI and spacer device with weight and severity based dosing. For weight less than 20 kg: mild and moderate disease 540mcg of albuterol per dose. For weight greater than or equal to 20 kg: mild disease 540 mcg of albuterol per dose and moderate disease 1080 mcg of albuterol per dose. Metered Dose Inhaler: A metered dose inhaler (MDI) is a small hand held pressurized canister device that contains both a medication, in this case albuterol, and a propellant. Pressing the device delivers 90mcg of albuterol. The MDI is attached to a spacer device, which is a one way holding chamber which allows the medication to be delivered over a series of breaths.	Albuterol Breath Actuated Nebulizer n=445 Participants Subjects randomized to BAN were evaluated for proper breath actuation technique. The device settings were changed to provide continuous nebulization with a facemask if the patient could not breath actuate. Children presenting in the mild and moderate severity category weighing less than 20kg, received 2500mcg of albuterol. Children weighing more than 20kg, received 2500mcg of albuterol if their presentation met mild severity criteria, or 5000mcg if they met moderate criteria. Breath Actuated Nebulizer: The breath actuated nebulizer (BAN) device is a device that converts liquid medication, into an aerosol. It consists of a mouthpiece, a medication reservoir, and connective tubing that attaches to a compressor. This BAN device delivers medication when the patient takes a breath, but it can be attached to a mask and set to continuous nebulization for patients that are not able to coordinate their breaths.
Number of Participants Requiring Repeat Visits	5 Participants	4 Participants

Adverse Events

Albuterol by Metered Dose Inhaler

Serious events: 0 serious events

Other events: 101 other events

Deaths: 0 deaths

Albuterol Breath Actuated Nebulizer

Serious events: 0 serious events

Other events: 141 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Albuterol by Metered Dose Inhaler n=445 participants at risk Albuterol administered via MDI and spacer device with weight and severity based dosing. For weight less than 20 kg: mild and moderate disease 540mcg of albuterol per dose. For weight greater than or equal to 20 kg: mild disease 540 mcg of albuterol per dose and moderate disease 1080 mcg of albuterol per dose. Metered Dose Inhaler: A metered dose inhaler (MDI) is a small hand held pressurized canister device that contains both a medication, in this case albuterol, and a propellant. Pressing the device delivers 90mcg of albuterol. The MDI is attached to a spacer device, which is a one way holding chamber which allows the medication to be delivered over a series of breaths.	Albuterol Breath Actuated Nebulizer n=445 participants at risk Subjects randomized to BAN were evaluated for proper breath actuation technique. For subjects unable to breath actuate, the RT attached an appropriately sized mask to the device, changed the setting to continuous nebulization and returned upon completion of the treatment. Albuterol dosing was based upon the subject's weight and presenting symptom severity. Children presenting in the mild and moderate severity category weighing less than 20kg, received 2500mcg of albuterol. Children weighing more than 20kg, received 2500mcg of albuterol if their presentation met mild severity criteria, or 5000mcg if they met moderate criteria. Breath Actuated Nebulizer: The breath actuated nebulizer (BAN) device is a device that converts liquid medication, in this case albuterol, into an aerosol. It consists of a mouthpiece, a medication reservoir, and connective tubing that attaches to a compressor. This BAN device delivers medication when the patient takes a breath, but it can be atta
Cardiac disorders Tachycardia	22.7% 101/445 • Number of events 101	31.7% 141/445 • Number of events 141

Additional Information

Mark Snider DO, Principal Investigator

University of Tennessee Health Sciences College of Medicine/Le Bonheur Children's Hospital

Phone: 9012875986

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place