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

A Phase IIb Randomized, Placebo-controlled, Double-blind Trial of Azithromycin to Eradicate Ureaplasma Respiratory Tract Infection in Preterm Infants

The purpose of this study is to determine whether intravenous azithromycin is effective in eradicating Ureaplasma respiratory tract infection in preterm infants born at 24 to 28 weeks gestation.

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.