Clinical trial NCT02447250: Preterm Infant Inhaled Albuterol Dosing
Official title: Albuterol Dose-Response on Pulmonary Function Testing in Preterm Infants at Risk of Bronchopulmonary Dysplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bronchopulmonary Dysplasia
Very Low Birth Weight
Keywords: Bronchopulmonary dysplasia
very low birth weight
albuterol
pulmonary function test
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2015-05-18
Enrollment: 14
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Change in Respiratory Resistance
timeFrame: Within one week of performing pulmonary function tests
Secondary outcomes:
measure: Number of Participants With Positive Response at Different Albuterol Doses
timeFrame: Data collected 15 minutes after dose in each session. Study includes 3 sessions within a 7 day period.
measure: Birth Weight of Albuterol Responders vs Non Responders
timeFrame: within one week of entering study
measure: Gestational Age at Birth
timeFrame: within one week of entering study
measure: Etiology of Preterm Delivery
timeFrame: within one week of entering study
Other outcomes:
measure: Family History of Asthma and Likelihood to Respond to Albuterol
timeFrame: History collected at enrollment, albuterol response assessed within one week
measure: Maternal BMI at Time of Pregnancy and Likelihood of Positive Response to Albuterol
timeFrame: Maternal information collected at enrollment; albuterol response assessed within one week
measure: Association of Smoke Exposure During Pregnancy and Neonatal Response to Albuterol
timeFrame: Smoking and second hand smoke exposure history will be obtained at enrollment. Albuterol response will be obtained within one week.
Locations:
city: Portland
country: United States
facility: Doernbecher Neonatal Care Center at Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Cynthia McEvoy, MD, MCR
role: PRINCIPAL_INVESTIGATOR
affiliation: Oregon Health and Science University
name: Amanda Kim, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.