Preterm Infant Inhaled Albuterol Dosing

Phase 4

Completed

• Conditions: Bronchopulmonary Dysplasia; Very Low Birth Weight
• Interventions: Drug: Varied albuterol dose response

• Registration Number: NCT02447250
• Lead Sponsor: Oregon Health and Science University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2013-10-24
• Primary Completion: 2014-12-30
• Study Completion: 2014-12-30
• Study First Submitted: 2015-05-14
• Study First Submitted QC: 2015-05-15
• Study First Posted: 2015-05-18
• Results First Submitted: 2018-10-16
• Status Verified: 2019-05
• Results First Submitted QC: 2019-05-03
• Last Update Submitted: 2019-05-03
• Results First Posted: 2019-05-23
• Last Update Posted: 2019-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm: varied albuterol dose response	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.

Primary Outcome Measures

Name	Time	Method
Change in Respiratory Resistance	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.

Secondary Outcome Measures

Name	Time	Method
Birth Weight of Albuterol Responders vs Non Responders	within one week of entering study	birth weight in grams of each subject was recorded at time of enrollment
Number of Participants With Positive Response at Different Albuterol Doses	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
Gestational Age at Birth	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	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).

Trial Locations

Locations (1)

Doernbecher Neonatal Care Center at Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States