Preterm Infant Inhaled Albuterol Dosing

• ClinicalTrials.gov Identifier: NCT02447250
• Recruitment Status: Completed
• First Posted: May 18, 2015
• Results First Posted: May 23, 2019
• Last Update Posted: May 23, 2019
• Sponsor: Oregon Health and Science University
• Information provided by (Responsible Party): Cynthia McEvoy, Oregon Health and Science University

Tracking Information

• First Submitted Date: May 14, 2015
• First Posted Date: May 18, 2015
• Results First Submitted Date: October 16, 2018
• Results First Posted Date: May 23, 2019
• Last Update Posted Date: May 23, 2019
• Actual Study Start Date: October 24, 2013
• Actual Primary Completion Date: December 30, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 3, 2019)

Change in Respiratory Resistance [ Time Frame: Within one week of performing pulmonary function tests ]

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.

Original Primary Outcome Measures (submitted: May 15, 2015)

Change in Respiratory Resistance [ Time Frame: Within one week of performing pulmonary function tests ]

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.

• Change History: Complete list of historical versions of study NCT02447250 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: May 3, 2019)

• Number of Participants With Positive Response at Different Albuterol Doses [ Time Frame: Data collected 15 minutes after dose in each session. Study includes 3 sessions within a 7 day period. ]
  Compare number of subjects who have a positive response (greater than or equal to 10% decrease in respiratory resistance) to each dose of albuterol
• Birth Weight of Albuterol Responders vs Non Responders [ Time Frame: within one week of entering study ]
  birth weight in grams of each subject was recorded at time of enrollment
• Gestational Age at Birth [ Time Frame: within one week of entering study ]
  Average gestational age (GA) in weeks at birth for subjects who responded to albuterol versus subjects without a positive response
• Etiology of Preterm Delivery [ Time Frame: within one week of entering study ]
  Reason for each subject's preterm delivery was classified as either preterm labor or delivery for maternal indications (eg pre-eclampsia).

Original Secondary Outcome Measures (submitted: May 15, 2015)

Comparison of responses to different albuterol doses [ Time Frame: Data collected 15 minutes after dose in each session. Study includes 3 sessions within a 7 day period. ]

Compare number of subjects who have a positive response (greater than or equal to 10% decrease in respiratory resistance) to each dose of albuterol

Current Other Pre-specified Outcome Measures (submitted: May 3, 2019)

• Family History of Asthma and Likelihood to Respond to Albuterol [ Time Frame: History collected at enrollment, albuterol response assessed within one week ]
  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.
• Maternal BMI at Time of Pregnancy and Likelihood of Positive Response to Albuterol [ Time Frame: Maternal information collected at enrollment; albuterol response assessed within one week ]
  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).
• Association of Smoke Exposure During Pregnancy and Neonatal Response to Albuterol [ Time Frame: Smoking and second hand smoke exposure history will be obtained at enrollment. Albuterol response will be obtained within one week. ]
  Mothers who smoked cigarettes during pregnancy and the rate of albuterol response of their infants

Original Other Pre-specified Outcome Measures (submitted: May 15, 2015)

• Family History of Asthma and Likelihood to Respond to Albuterol [ Time Frame: History collected at enrollment, albuterol response assessed within one week ]
• Maternal BMI at Time of Pregnancy and Likelihood of Positive Response to Albuterol [ Time Frame: Maternal information collected at enrollment; albuterol response assessed within one week ]
  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 high BMI (>30).
• Association of Smoke Exposure During Pregnancy and Neonatal Response to Albuterol [ Time Frame: Smoking and second hand smoke exposure history will be obtained at enrollment. Albuterol response will be obtained within one week. ]

Descriptive Information

• Brief Title: Preterm Infant Inhaled Albuterol Dosing
• Official Title: Albuterol Dose-Response on Pulmonary Function Testing in Preterm Infants at Risk of Bronchopulmonary Dysplasia
• Brief Summary: The purpose of this study is to help determine the best dose of inhaled albuterol sulfate in premature babies at risk of developing bronchopulmonary dysplasia (BPD). BPD is the chronic lung disease of prematurity and is associated with increased morbidity and mortality, longer hospital stays, and increased healthcare utilization. Albuterol is an inhaled medication frequently used in premature infants with chronic lung disease and in people with asthma. It is believed to be safe, but the optimal dose for infants is not clear. The investigators hypothesize that albuterol may help a subset of premature infants with lung disease, but they need to determine the best dose prior to doing research about how effective it is for chronic lung disease/BPD. Response to each of three doses of albuterol will be measure using pulmonary function tests.

Detailed Description

1. Recruitment: Subjects at risk for developing bronchopulmonary dysplasia will be recruited from the Doernbecher Neonatal Care Center (DNCC).The subjects' mother will be approached by the investigators and consent obtained if she agrees to participate.
2. Medical Record and Interview: Information about the pregnancy, delivery, and neonatal course will be obtained from the medical record. This will include maternal body mass index (BMI) at first prenatal visit, maternal age and parity, birthweight, gestational age at birth, history of maternal betamethasone for fetal lung maturation, indication for preterm delivery (e.g. pre-eclampsia, preterm labor), surfactant administration, history of intubations and duration of mechanical ventilation in the infant, current level of respiratory support, use of diuretics, bronchodilators, and corticosteroids in the neonate. A brief interview will also be obtained from the subject's mother. The questions asked will involve tobacco exposure during the pregnancy and family history of asthma. The purpose of the data collected on the infant's mother is to help identify factors that may predict which premature infants will respond to albuterol.
3. Procedures: Pulmonary function tests (PFTs) are the procedures involved in this study. PFTs are non-invasive, require no sedation, and are commonly used to provide standard medical care to preterm infants in the DNCC. PFTs involve placing a mask over the nose and mouth during quiet sleep. We will record flow-volume loops with passive respiration and measure respiratory compliance and passive respiratory resistance (Rr) using the single breath occlusion technique. A dose of albuterol will be given after baseline measurements are obtained; the PFTs will be repeated 15 minutes after administration. The testing will be the same for each of the three sessions, except the dose of albuterol will be altered each session (see below). There will be only one session per day, and all three sessions will occur within a 7 day period. Vital signs (respiratory rate, heart rate, oxygen saturation) will be continuously monitored during the testing.
4. Study Drug: Albuterol is a bronchodilator frequently prescribed in neonatal ICUs to help treat the symptoms of BPD. About 50% of preterm infants in the DNCC with evolving BPD have shown an improvement in their PFT after 2 puffs (180 micrograms) of albuterol (unpublished data). The typical dosing is 2-4 puffs every 4-6 hours but the optimal dose in premature infants is not known. In this study, 2 puffs (180 micrograms) will be given on the first day of PFTs, 3 puffs (270 micrograms) the second day, and 4 puffs (260 micrograms) on the third day.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Bronchopulmonary Dysplasia
• Very Low Birth Weight

Intervention

Drug: 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 33w6d. 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 sinlge 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.

Other Names:

• Albuterol sulfate
• Salbutamol
• Proventil
• ProAir
• Ventolin

Study Arms

Experimental: Single Arm: varied albuterol dose response

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.

Intervention: Drug: Varied albuterol dose response

Publications *

• Blake K, Madabushi R, Derendorf H, Lima J. Population pharmacodynamic model of bronchodilator response to inhaled albuterol in children and adults with asthma. Chest. 2008 Nov;134(5):981-989. doi: 10.1378/chest.07-2991. Epub 2008 Jun 26.
• Ng G, da Silva O, Ohlsson A. Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2012 Jun 13;(6):CD003214. doi: 10.1002/14651858.CD003214.pub2. Review. Update in: Cochrane Database Syst Rev. 2016 Dec 14;12 :CD003214.
• Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 3, 2019): 14
• Original Estimated Enrollment (submitted: May 15, 2015): 20
• Actual Study Completion Date: December 30, 2014
• Actual Primary Completion Date: December 30, 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• very low birthweight infant (<1500g)
• gestational age at birth <32 weeks
• age 14 or more days and corrected to 28w0d to 33w6d gestational age
• continuing to require respiratory support and/or supplemental oxygen

Exclusion Criteria:

• chromosomal abnormalities
• major congenital anomalies
• congenital heart disease, except atrial septal defect and patent ductus arteriosus
• clinical providers determine subject too unstable to undergo pulmonary function testing

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02447250
• Other Study ID Numbers: IRB00009883
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Cynthia McEvoy, Oregon Health and Science University
• Study Sponsor: Oregon Health and Science University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Cynthia McEvoy, MD, MCR; Oregon Health and Science University
• Study Director: Amanda Kim, MD; Oregon Health and Science University

• PRS Account: Oregon Health and Science University
• Verification Date: May 2019