Severe Bronchopulmonary Dysplasia
Conditions
Brief summary
Currently several dose schedules of Albuterol are administered via nebulization to infants in the neonatal and infant intensive care unit (N/IICU). As Albuterol is not FDA approved for this population (under 2 years) there is no standard recommended dose. Aerosolized Albuterol is one of the most widely used therapies that are utilized for infants with chronic lung disease. The common practice in the N/IICU is weight base dosing of all medications. This contradicts the aerosol science recommendations, which advise not to titrate doses by weight as the patient naturally self-regulates their dose according to the change in minute ventilation with age. In addition, the wide use of aerosolized Albuterol in the infant with Bronchopulmonary Dysplasia (BPD) has little current evidence of efficacy in this disease. Understanding the appropriate dose for effective treatment as well as the indication for use in the BPD population would provide the clinician with useful guidelines. The investigators propose to analyze the safety and efficacy of aerosolized albuterol in infants with BPD comparing the recommended dose per aerosolization literature with the common dosing practices at The Children's Hospital of Philadelphia (CHOP) as well as placebo.
Detailed description
This is a randomized, blinded cross-over study of infants with a diagnosis of Severe BPD that are mechanically ventilated. Participants will receive 3 sets of treatment (2.5mg Albuterol, 1.25mg Albuterol, 3ml normal saline placebo), in random order. Each treatment will be administered every 4 hours for 24 hours. After a 6 hour washout phase, the next group of interventions will be applied. Following another wash-out phase, the final group of intervention will be applied. Pulmonary mechanics from the ventilator (e.g. airway compliance, airway resistance, tidal volume, peak inspiratory pressure, Forced Expiratory Flow at 75% of forced vital capacity, etc.) and the patient short term response to therapy (heart rate, blood pressure, heart rhythm) will be assessed for the duration of the treatment period.
Interventions
Subjects will receive a dose of study medication every 4 hours for 24 total hours
DRUGSterile Saline
Subjects will receive a dose of study medication every 4 hours for 24 total hours
Sponsors
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
No
Inclusion criteria
1. Infants greater than or equal to 36 weeks corrected gestational age to one year of age 2. Diagnosis of BPD in accordance with The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) definition 3. May have a current order for short acting bronchodilator, not required 4. May have congenital anomalies unless one or more of the
Exclusion criteria
are met, not required 5. Receiving conventional mechanical ventilation via an artificial airway (endotracheal tube or tracheostomy) via Draeger V500 Ventilator 6. Parental/guardian permission (informed consent)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Expiratory Flow Between Pre and Post-medication Dosing | every 4 hours in each treatment group, up to 24 hours | Expiratory flow at 75% of vital capacity (EF75) will be measured before beginning each treatment and again 15-30 min after each treatment phase. Therefore there will be 6 pairs (12) of EF values to determine the change in EF for each treatment. this measure is done by measuring the expiratory flow at 75% of exhalation on as measure on the flow volume loop of the ventilator. a single mechanical breath is chosen and the flow volume loop is frozen on the ventilator screen. the clinician can then scroll to measure total tidal volume for the breath, then multiple this volume by 0.25 (to ascertain the volume that the time point of 75% of exhalation), then scroll along the expiratory side of the flow volume loop until the calculated volume is reached and then the flow at that time point is recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Heart Rate (Beats/Min) Between Pre and Post-medication Dosing | every 4 hours in each treatment group, up to 24 hours | Heart rate will be measured before beginning each treatment and again 15-30 min after the conclusion of each treatment phase (4 hours). Therefore there will be 6 pairs of heart rates (12 measures), to determine the change in HR for each treatment group. |
Countries
United States
Participant flow
Pre-assignment details
The original study sample size called for 25 subjects. The block randomization scheme of 6 treatment sequences within 1 randomization block. Therefore we recruited 24 patients to complete 4 randomization block. the 25th patient would have started a new randomization block and make one treatment sequence more common that the others.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study This was a crossover study therefore all patients were scheduled to receive all 3 treatment groups. Enrollment demographics will be the same for all groups. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 170.4 days STANDARD_DEVIATION 49.4 |
| Birth Gestational Age | 25 weeks STANDARD_DEVIATION 1.9 |
| Birth Weight | 611 g STANDARD_DEVIATION 12 |
| Corrected Gestational Age | 49 Weeks STANDARD_DEVIATION 6.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 14 Participants |
| Weight | 4.7 kg STANDARD_DEVIATION 1.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 0 / 23 | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Change in Expiratory Flow Between Pre and Post-medication Dosing
Expiratory flow at 75% of vital capacity (EF75) will be measured before beginning each treatment and again 15-30 min after each treatment phase. Therefore there will be 6 pairs (12) of EF values to determine the change in EF for each treatment. this measure is done by measuring the expiratory flow at 75% of exhalation on as measure on the flow volume loop of the ventilator. a single mechanical breath is chosen and the flow volume loop is frozen on the ventilator screen. the clinician can then scroll to measure total tidal volume for the breath, then multiple this volume by 0.25 (to ascertain the volume that the time point of 75% of exhalation), then scroll along the expiratory side of the flow volume loop until the calculated volume is reached and then the flow at that time point is recorded.
Time frame: every 4 hours in each treatment group, up to 24 hours
Population: Each subject had the potential for 6 paired observations (12 measures) per treatment group (comparison of measure before and after each dose of the study drug). 2 subjects did not complete all 3 treatment groups. Some measurements were missed leaving less than the total potential number of observations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Dose Albuterol Sulfate | Change in Expiratory Flow Between Pre and Post-medication Dosing | 0.38 L/min | Standard Deviation 2.3 |
| Half Dose Albuterol Sulfate | Change in Expiratory Flow Between Pre and Post-medication Dosing | 0.70 L/min | Standard Deviation 2.4 |
| Sterile Saline | Change in Expiratory Flow Between Pre and Post-medication Dosing | 0.45 L/min | Standard Deviation 2.5 |
Secondary
Percent Change in Heart Rate (Beats/Min) Between Pre and Post-medication Dosing
Heart rate will be measured before beginning each treatment and again 15-30 min after the conclusion of each treatment phase (4 hours). Therefore there will be 6 pairs of heart rates (12 measures), to determine the change in HR for each treatment group.
Time frame: every 4 hours in each treatment group, up to 24 hours
Population: There was a potential for up to 6 paired observations (12 measures) per treatment group. 2 patients did not complete all 3 treatment groups resulting is lower number of observations for the potential total.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Dose Albuterol Sulfate | Percent Change in Heart Rate (Beats/Min) Between Pre and Post-medication Dosing | 0.074 % change | Standard Deviation 0.129 |
| Half Dose Albuterol Sulfate | Percent Change in Heart Rate (Beats/Min) Between Pre and Post-medication Dosing | 0.031 % change | Standard Deviation 0.12 |
| Sterile Saline | Percent Change in Heart Rate (Beats/Min) Between Pre and Post-medication Dosing | 0.009 % change | Standard Deviation 0.084 |