Trial of Intravenous Azithromycin to Eradicate Ureaplasma Respiratory Tract Infection in Preterm Infants

The study design will be a double-blind, placebo-controlled clinical trial to test the
efficacy and safety of azithromycin 20 mg/kg x 3 days to eradicate Ureaplasma spp from the
respiratory tract of preterm infants 24 weeks 0 days to 28 weeks 6 days gestation exposed to
positive pressure ventilation. The primary outcome will be survival with microbiological
eradication of Ureaplasma defined as survival to discharge or transfer with 3 negative
cultures obtained post-therapy. Secondary outcomes will include physiologic BPD at 36 weeks
post-menstrual age (PMA), overall mortality, incidence of co-morbidities of prematurity such
as intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis,
bacterial and fungal nosocomial infection, pulmonary air leak, patent ductus arteriosus,
retinopathy of prematurity, number of days of positive pressure ventilation, number of days
of oxygen supplementation, use of postnatal steroids, and use of non-study antibiotics. At 6
and 18 months adjusted age, a pulmonary outcome questionnaire will be administered by phone
or in person interview. At 18-22 months adjusted age, neurodevelopmental outcomes will be
assessed by 1) Bayley Scale of Infant and Toddler Development, 3rd edition (BSID-III); 2)
Amiel-Tison neurologic examination; 3) Gross Motor Function Classification System; and 4)
medical record review for hearing impairment with or without amplification and vision
impairment (vision <20/200).

Inclusion Criteria:

- Gestational age 24 weeks 0 days-28weeks 6 days by best obstetrical estimate

- <72 h age

- Positive pressure ventilation for at least 1 hour duration during the first 72 hours
of life

- Presence of indwelling intravenous line for drug administration

Exclusion Criteria:

- Any patient judged to be non-viable or for whom withdrawal of life support is planned

- Patients with major lethal congenital anomalies

- Triplets or higher order multiples

- Patients delivered for maternal indications (low risk of Ureaplasma colonization)

- Patients with EKG QT interval corrected for heart rate (Qtc) ≥ 450 ms

- Patients with significant hepatic impairment (direct bilirubin >1.5 mg/dL)

- Patients exposed to other systemic macrolide

- Patients with clinically suspected Ureaplasma central nervous system (CNS) infection
or other confirmed bacterial/viral infection

- Patients participating in other clinical trials involving investigational products.