A Phase IIb Randomized, Placebo-controlled, Double-blind Trial of Azithromycin to Eradicate Ureaplasma Respiratory Tract Infection in Preterm Infants
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Ureaplasma Infections
- Sponsor
- University of Maryland, Baltimore
- Enrollment
- 121
- Locations
- 7
- Primary Endpoint
- Number of Participants With Survival And Transfer From NICU With Microbiological Eradication of Ureaplasma
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Detailed Description
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).
Investigators
Rose Viscardi
Professor of Pediatrics
University of Maryland, Baltimore
Eligibility Criteria
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.
Arms & Interventions
Placebo (5% dextrose)
Placebo
Intervention: Placebo
Azithromycin
Azithromycin intravenous (2 mg/ml) 20 mg/kg every 24h x 3 days
Intervention: Azithromycin
Outcomes
Primary Outcomes
Number of Participants With Survival And Transfer From NICU With Microbiological Eradication of Ureaplasma
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Bacterial clearance (eradication) will be defined as 3 negative cultures obtained 2 and 5 days post-third dose and 21 d of age. Survival is defined as survival at time of discharge or transfer from the neonatal intensive care unit (NICU).
Secondary Outcomes
- Number of Participants Who Survived Until 36 Wks Postmenstrual Age With Physiologic Defined Bronchopulmonary Dysplasia (BPD) at 36 Weeks Post Menstrual Age(36 weeks post menstrual age (one month prior to due date))
- Number of Participants With Death or Neurodevelopmental Impairment(22-26 months)
- Number of Participants With Pulmonary Impairment(6-26 months)
- Number of Participants Who Died(22-26 months)
- Duration of Positive Pressure Support(Participants will be followed for the duration of hospital stay, an expected average of 10 weeks)
- Duration of Oxygen Supplementation(Participants will be followed for the duration of hospital stay, an expected average of 10 weeks)
- Number of Participants Who Experienced Air Leaks(Participants will be followed for the duration of hospital stay, an expected average of 10 weeks)
- Number of Participants Who Received Postnatal Steroids(36 weeks)
- Number of Participants Who Received Non-Study Antibiotics(Participants will be followed for the duration of hospital stay, an expected average of 10 weeks)
- Pharmacokinetics (PK)/Pharmacodynamics (PD) Modelling of Time Course of Azithromycin Plasma Concentrations(Study day 1-day 7)