Bronchopulmonary Dysplasia
Conditions
Keywords
premature infant, respiratory distress syndrome, mechanical ventilation
Brief summary
The hypothesis of this study is that administration of azithromycin to ventilated premature infants will decrease the incidence and severity of BPD. The purpose of this study is to determine if Azithromycin treatment is beneficial for prevention of bronchopulmonary dysplasia in preterm infants.
Detailed description
The survival of preterm infants has increased dramatically and has been associated with an increase in BPD. The incidence of BPD among extremely low birthweight infants ranges from 45% to 90%. Development of BPD is associated with both antenatal (maternal chorioamnionitis often due to Ureaplasma is related to BPD) and postnatal complications (oxygen toxicity, barotrauma, late onset infections). These insults appear to lead to an inflammatory response with resultant arrest of normal alveolar and vascular development. Multiple human studies support the role of inflammation in the development of BPD. Evaluating a medication that could decrease the inflammation in BPD, with minimal side effects, could significantly improve the morbidities of prematurity and the financial burden incurred by parents. Macrolide antibiotics (erythromycin and azithromycin) have been shown to have anti-inflammatory properties that are independent of their antimicrobial properties. Azithromycin has the potential to decrease the severity of ventilator-induced pulmonary inflammation that is commonly seen in BPD.
Interventions
DRUGAzithromycin
Give 10 mg/kg IV/PO daily for first 7 days, then give 5 mg/kg IV/PO daily for 35 days.
DRUGPlacebo
vehicle dose given daily, IV/PO, same volume that Azithromycin would be to equal 10 mg/kg for first 7 days, then 5 mg/kg for 5 weeks.
Sponsors
American Lung Association
Hubert Ballard
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 72 Hours
Healthy volunteers
No
Inclusion criteria
* birthweight less than 1250 grams admitted to UK NICU * mechanical ventilation within the first 72 hours of life
Exclusion criteria
* confirmed sepsis by blood culture * multiple congenital anomalies or known syndromes * intrauterine growth retardation with birthweight less than 10%ile for gestational age * ROM for \>7 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Bronchopulmonary Dysplasia (BPD) | diagnosis of BPD at 36wks corrected gestational age | comparison of the % Incidence of bronchopulmonary dysplasia (BPD) for the azithromycin vs placebo groups. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Postnatal Steroid Use | Duration of NICU stay, up to 16 weeks, average stay is about 10 weeks | Steroids will be provided as needed based on Standard of Care. Data are presented as the percent of participants that received steroids between birth and discharge from the NICU. |
| Number of Days on Mechanical Ventilation | Duration of NICU stay, up to 16 weeks, average stay is about 10 weeks | Participants will be placed on mechanical ventilation as necessary based on standard of care. Data are presented as the percent of participants in each group receiving mechanical ventilation. |
| Participant Mortality | Duration of NICU stay, up to 16 weeks, average stay is about 10 weeks | Data will be collected on the number of participants that did not survive to discharge from the NICU. Data are presented as the percent of participants that did not survive. |
Countries
United States
Participant flow
Recruitment details
The study recruitment started 9/04 ended 8/08. All subjects were enrolled after admission to NICU. Randomized treatment started within 12 hrs of beginning ventilatory support. If outborn, consent was obtained from parent(s) after phone discussion by the research staff. The consents were faxed, witnessed and brought back by the Transport Team.
Participants by arm
| Arm | Count |
|---|---|
| Azith Group Azithromycin : Give 10 mg/kg IV/PO daily for first 7 days, then give 5 mg/kg IV/PO daily for 35 days. | 111 |
| Placebo Group D5W : Dose given daily, IV/PO, same volume that Azithromycin would be to equal 10 mg/kg for first 7 days, then 5 mg/kg for 5 weeks. | 109 |
| Total | 220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 20 | 24 |
Baseline characteristics
| Characteristic | Placebo Group | Azith Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 109 Participants | 111 Participants | 220 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 26 gestational age, weeks STANDARD_DEVIATION 1.6 | 25.7 gestational age, weeks STANDARD_DEVIATION 1.5 | 25.85 gestational age, weeks STANDARD_DEVIATION 1.55 |
| Region of Enrollment United States | 109 participants | 111 participants | 220 participants |
| Sex: Female, Male Female | 59 Participants | 49 Participants | 108 Participants |
| Sex: Female, Male Male | 50 Participants | 62 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 111 | 24 / 109 |
| other Total, other adverse events | 0 / 111 | 0 / 109 |
| serious Total, serious adverse events | 0 / 111 | 0 / 109 |
Outcome results
Primary
Incidence of Bronchopulmonary Dysplasia (BPD)
comparison of the % Incidence of bronchopulmonary dysplasia (BPD) for the azithromycin vs placebo groups.
Time frame: diagnosis of BPD at 36wks corrected gestational age
Population: Mortality was 18% in the Azithromycin group and 22% in the Placebo group, thus 91 participants in the Azithromycin group and 85 participants in the Placebo group were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azith Group | Incidence of Bronchopulmonary Dysplasia (BPD) | 76 percentage w/ BPD |
| Placebo Group | Incidence of Bronchopulmonary Dysplasia (BPD) | 84 percentage w/ BPD |
p-value: 0.2Chi-squared
Other Pre-specified
Number of Days on Mechanical Ventilation
Participants will be placed on mechanical ventilation as necessary based on standard of care. Data are presented as the percent of participants in each group receiving mechanical ventilation.
Time frame: Duration of NICU stay, up to 16 weeks, average stay is about 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azith Group | Number of Days on Mechanical Ventilation | 28 days | Standard Deviation 26 |
| Placebo Group | Number of Days on Mechanical Ventilation | 26 days | Standard Deviation 26 |
Other Pre-specified
Participant Mortality
Data will be collected on the number of participants that did not survive to discharge from the NICU. Data are presented as the percent of participants that did not survive.
Time frame: Duration of NICU stay, up to 16 weeks, average stay is about 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azith Group | Participant Mortality | 18 percentage of mortality |
| Placebo Group | Participant Mortality | 22 percentage of mortality |
Other Pre-specified
Postnatal Steroid Use
Steroids will be provided as needed based on Standard of Care. Data are presented as the percent of participants that received steroids between birth and discharge from the NICU.
Time frame: Duration of NICU stay, up to 16 weeks, average stay is about 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azith Group | Postnatal Steroid Use | 18 percentage of participants |
| Placebo Group | Postnatal Steroid Use | 22 percentage of participants |