Trial Outcomes & Findings for Preterm Infant Inhaled Albuterol Dosing (NCT NCT02447250)
NCT ID: NCT02447250
Last Updated: 2019-05-23
Results Overview
The primary outcome is the percentage of subjects who show a positive response to each dose of albuterol. A positive response is defined as a greater than or equal to 10% decrease in respiratory resistance (Rrs). The change in RRs was measured at baseline and again after each dose of albuterol. All measurements were taken within a 7 day time frame for each subject such that each subject would have up to 3 results measured during a 7 day period, if he/she were able to complete three sets of PFTs according to study protocol. The change in Rrs was calculated by subtracting the baseline Rrs from the post-albuterol Rrs.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
14 participants
Primary outcome timeframe
Within one week of performing pulmonary function tests
Results posted on
2019-05-23
Participant Flow
1 subject was consented into the study, but then became too clinically unstable to participate in the study and remained unstable throughout the eligibility period.
Participant milestones
| Measure |
Single Arm: Varied Albuterol Dose Response
Subjects will be evaluated in three sessions within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
First Dose (180 mcg Albuterol)
STARTED
|
14
|
|
First Dose (180 mcg Albuterol)
COMPLETED
|
14
|
|
First Dose (180 mcg Albuterol)
NOT COMPLETED
|
0
|
|
Second Dose (270 mcg Albuterol)
STARTED
|
14
|
|
Second Dose (270 mcg Albuterol)
COMPLETED
|
13
|
|
Second Dose (270 mcg Albuterol)
NOT COMPLETED
|
1
|
|
Third Dose (360 mcg Albuterol)
STARTED
|
13
|
|
Third Dose (360 mcg Albuterol)
COMPLETED
|
8
|
|
Third Dose (360 mcg Albuterol)
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Single Arm: Varied Albuterol Dose Response
Subjects will be evaluated in three sessions within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Second Dose (270 mcg Albuterol)
elevated HR with first dose
|
1
|
|
Third Dose (360 mcg Albuterol)
Clinically unstable, unable to do PFT
|
1
|
|
Third Dose (360 mcg Albuterol)
Elevated HR with 2nd dose
|
4
|
Baseline Characteristics
Preterm Infant Inhaled Albuterol Dosing
Baseline characteristics by cohort
| Measure |
Single Arm: Varied Albuterol Dose Response
n=14 Participants
Subjects will be evaluated in three sessions within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Age, Continuous
|
36 days
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
birthweight
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895 grams
n=5 Participants
|
|
gestational age at birth
|
26.9 weeks
n=5 Participants
|
|
respiratory support at study entry, CPAP
|
12 Participants
n=5 Participants
|
|
respiratory support at study entry, mechanical ventilation
|
2 Participants
n=5 Participants
|
|
history of any mechanical ventilation
|
8 Participants
n=5 Participants
|
|
received surfactant
|
7 Participants
n=5 Participants
|
|
received antenatal corticosteroids
|
13 Participants
n=5 Participants
|
|
ever received albuterol prior to study entry
|
0 Participants
n=5 Participants
|
|
received diuretics prior to study entry
|
3 Participants
n=5 Participants
|
|
reason for preterm delivery: preterm labor
|
6 Participants
n=5 Participants
|
|
maternal age, years (mean)
|
26.4 years
n=5 Participants
|
|
maternal BMI (mean, range)
|
25.5 kg/ m^2
n=5 Participants
|
|
maternal diabetes mellitus (pregestational or gestational)
|
4 Participants
n=5 Participants
|
|
family history of asthma
|
2 Participants
n=5 Participants
|
|
maternal smoking during pregnancy
|
4 Participants
n=5 Participants
|
|
second hand smoke exposure during pregnancy
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Within one week of performing pulmonary function testsPopulation: Some subjects did not receive all 3 doses (based on how they tolerated initial dose(s))
The primary outcome is the percentage of subjects who show a positive response to each dose of albuterol. A positive response is defined as a greater than or equal to 10% decrease in respiratory resistance (Rrs). The change in RRs was measured at baseline and again after each dose of albuterol. All measurements were taken within a 7 day time frame for each subject such that each subject would have up to 3 results measured during a 7 day period, if he/she were able to complete three sets of PFTs according to study protocol. The change in Rrs was calculated by subtracting the baseline Rrs from the post-albuterol Rrs.
Outcome measures
| Measure |
Single Arm: Varied Albuterol Dose Response
n=11 Participants
Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Change in Respiratory Resistance
dose 1
|
0.011 cm h2o/mL/sec
Standard Deviation 0.016
|
|
Change in Respiratory Resistance
dose 2
|
0.006 cm h2o/mL/sec
Standard Deviation 0.008
|
|
Change in Respiratory Resistance
dose 3
|
0.014 cm h2o/mL/sec
Standard Deviation 0.014
|
SECONDARY outcome
Timeframe: Data collected 15 minutes after dose in each session. Study includes 3 sessions within a 7 day period.Population: Measuring Rrs can be technically challenging, particularly in premature infants, and we did not have measurable Rrs for every subject at every time point, therefore the denominator here is not the same as the total number of participants. For example, we have missing/unmeasurable Rrs for 3 subjects at the lowest albuterol dose.
Compare number of subjects who have a positive response (greater than or equal to 10% decrease in respiratory resistance) to each dose of albuterol
Outcome measures
| Measure |
Single Arm: Varied Albuterol Dose Response
n=14 Participants
Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Number of Participants With Positive Response at Different Albuterol Doses
positive Rrs response at 180 mcg albuterol
|
6 participants
|
|
Number of Participants With Positive Response at Different Albuterol Doses
positive Rrs response at 270 mcg albuterol
|
4 participants
|
|
Number of Participants With Positive Response at Different Albuterol Doses
positive Rrs response at 360 mcg albuterol
|
4 participants
|
SECONDARY outcome
Timeframe: within one week of entering studyPopulation: This data included 10 subjects who responded to albuterol at at least one dose, and 3 subjects who did not show a positive response to albuterol at any dose
birth weight in grams of each subject was recorded at time of enrollment
Outcome measures
| Measure |
Single Arm: Varied Albuterol Dose Response
n=13 Participants
Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Birth Weight of Albuterol Responders vs Non Responders
albuterol responders
|
847.2 grams
Standard Deviation 296
|
|
Birth Weight of Albuterol Responders vs Non Responders
albuterol non responders
|
1147.7 grams
Standard Deviation 216
|
SECONDARY outcome
Timeframe: within one week of entering studyPopulation: We have data for 10 subjects who responded to albuterol and 3 subjects who did not respond.
Average gestational age (GA) in weeks at birth for subjects who responded to albuterol versus subjects without a positive response
Outcome measures
| Measure |
Single Arm: Varied Albuterol Dose Response
n=13 Participants
Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Gestational Age at Birth
birth GA albuterol responders, weeks
|
26.7 weeks
Standard Deviation 1.9
|
|
Gestational Age at Birth
birth GA albuterol non responders
|
28.5 weeks
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: within one week of entering studyPopulation: 5 subjects were delivered due to preterm labor, and 8 delivered prematurely due to maternal indications
Reason for each subject's preterm delivery was classified as either preterm labor or delivery for maternal indications (eg pre-eclampsia).
Outcome measures
| Measure |
Single Arm: Varied Albuterol Dose Response
n=13 Participants
Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Etiology of Preterm Delivery
preterm labor, responsive to albuterol
|
4 Participants
|
|
Etiology of Preterm Delivery
maternal indicated delivery, responsive to albuter
|
6 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: History collected at enrollment, albuterol response assessed within one weekPopulation: only 2 subjects had a history of a first-degree relative (parent or sibling) with asthma
Family history was obtained from verbal history by subject's mother at time of enrollment in study. A positive family history was noted if a first degree relative of the subject (infant) had a diagnosis of asthma.
Outcome measures
| Measure |
Single Arm: Varied Albuterol Dose Response
n=14 Participants
Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Family History of Asthma and Likelihood to Respond to Albuterol
family hx of asthma, respond to albuterol
|
1 participants
|
|
Family History of Asthma and Likelihood to Respond to Albuterol
no fam hx asthma, respond to albuterol
|
9 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Maternal information collected at enrollment; albuterol response assessed within one weekPopulation: We have BMI data on 13 mothers.
Maternal BMI will be obtained from her medial record, and she will be asked about weight gain during pregnancy at time of enrollment. Results will be compared for infants born to women with a normal BMI vs. those with obese BMI (\>30).
Outcome measures
| Measure |
Single Arm: Varied Albuterol Dose Response
n=13 Participants
Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Maternal BMI at Time of Pregnancy and Likelihood of Positive Response to Albuterol
mean BMI mothers of albuterol-responders , any dos
|
27.4 kg/m^2
Standard Deviation 8.6
|
|
Maternal BMI at Time of Pregnancy and Likelihood of Positive Response to Albuterol
mean BMI mothers of albuterol non-responders
|
27.3 kg/m^2
Standard Deviation 3.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Smoking and second hand smoke exposure history will be obtained at enrollment. Albuterol response will be obtained within one week.Population: We have data for 9 subjects whose mothers did not smoke and 4 subjects whose mothers smoked
Mothers who smoked cigarettes during pregnancy and the rate of albuterol response of their infants
Outcome measures
| Measure |
Single Arm: Varied Albuterol Dose Response
n=13 Participants
Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. PFTs will be performed during quiet sleep while the baby is spontaneously breathing or while the baby is intubated and receiving mechanical ventilation. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in three sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 2
|
|---|---|
|
Association of Smoke Exposure During Pregnancy and Neonatal Response to Albuterol
albuterol responders of mothers who smoked
|
4 participants
|
|
Association of Smoke Exposure During Pregnancy and Neonatal Response to Albuterol
albuterol responders of non-smoker mothers %
|
6 participants
|
Adverse Events
Single Arm: Varied Albuterol Dose Response
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Single Arm: Varied Albuterol Dose Response
n=14 participants at risk
Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning after 14 days of age and at 28w0d to 33w6d corrected gestational age. In each session, pulmonary function tests (PFTs) will be performed prior to and 15 minutes after a dose of albuterol. The dose will be different in each session. In the first session, a single dose of 180 micrograms (2 puffs) of albuterol sulfate via metered dose inhaler. The dose will be 270 micrograms in the second session and 360 micrograms in the third session. Resistance and compliance will be measured using the single breath occlusion technique.
Varied albuterol dose response: Subjects will be evaluated in 3 sessions. The sessions will occur within a 7 day time span, beginning between 14 or more days from birth and at a corrected gestational age of 28w0d to
|
|---|---|
|
Cardiac disorders
elevated heart rate above predefined criteria
|
7.1%
1/14 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place