Preterm Infant Inhaled Albuterol Dosing

NCT ID: NCT02447250

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-24
• Study Completion Date: 2014-12-30

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.

Conditions

Bronchopulmonary Dysplasia; Very Low Birth Weight

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Varied albuterol dose response

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Albuterol sulfate; Salbutamol; Proventil; ProAir; Ventolin

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

• Minimum Eligible Age: 14 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Cynthia McEvoy

Associate Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cynthia McEvoy, MD, MCR

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Amanda Kim, MD

Role: STUDY_DIRECTOR

Oregon Health and Science University

Locations

Doernbecher Neonatal Care Center at Oregon Health & Science University

Portland, Oregon, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 18583517 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22696334 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11401896 (View on PubMed)

Other Identifiers

IRB00009883

Identifier Type: -

Identifier Source: org_study_id