Clinical trial NCT01778634: Trial of Intravenous Azithromycin to Eradicate Ureaplasma Respiratory Tract Infection in Preterm Infants
Official title: A Phase IIb Randomized, Placebo-controlled, Double-blind Trial of Azithromycin to Eradicate Ureaplasma Respiratory Tract Infection in Preterm Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ureaplasma Infections
Keywords: Ureaplasma parvum
Ureaplasma urealyticum
prematurity
bronchopulmonary dysplasia
azithromycin
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Mercy Medical Center
name: Johns Hopkins University
name: University of Virginia
name: University of Alabama at Birmingham
name: Christiana Care Health Services
First posted: 2013-01-29
Enrollment: 121
Sex: ALL
Minimum age (years): 2
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Number of Participants With Survival And Transfer From NICU With Microbiological Eradication of Ureaplasma
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Secondary outcomes:
measure: Number of Participants Who Survived Until 36 Wks Postmenstrual Age With Physiologic Defined Bronchopulmonary Dysplasia (BPD) at 36 Weeks Post Menstrual Age
timeFrame: 36 weeks post menstrual age (one month prior to due date)
measure: Number of Participants With Death or Neurodevelopmental Impairment
timeFrame: 22-26 months
measure: Number of Participants With Pulmonary Impairment
timeFrame: 6-26 months
measure: Number of Participants Who Died
timeFrame: 22-26 months
measure: Duration of Positive Pressure Support
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
measure: Duration of Oxygen Supplementation
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
measure: Number of Participants Who Experienced Air Leaks
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
measure: Number of Participants Who Received Postnatal Steroids
timeFrame: 36 weeks
measure: Number of Participants Who Received Non-Study Antibiotics
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
measure: Pharmacokinetics (PK)/Pharmacodynamics (PD) Modelling of Time Course of Azithromycin Plasma Concentrations
timeFrame: Study day 1-day 7
Other outcomes:
measure: Number of Participants With Threshold Retinopathy of Prematurity (ROP)
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
measure: Number of Participants With Necrotizing Enterocolitis (NEC)
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
measure: Number of Participants With Infections During the NICU Hospitalization
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
measure: Number of Participants With Severe Intraventicular Hemorrhage (IVH)
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
measure: Number of Participants With Periventricular Leukomalacia (PVL)
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
measure: Number of Participants With Patent Ductus Arteriosus (PDA)
timeFrame: 14 days
measure: Number of Participants With Cardiac Arrhythmia
timeFrame: 3 days
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Maryland, College Park
name: Rose M Viscardi, M.D.
role: STUDY_CHAIR
affiliation: Johns Hopkins University
name: Pamela Donohue, ScD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Namasivayam Ambalavanan, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: David A Kaufman, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland, College Park
name: Michael L Terrin, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mercy Medical Center
name: Susan J Dulkerian, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hassan HE, Othman AA, Eddington ND, Duffy L, Xiao L, Waites KB, Kaufman DA, Fairchild KD, Terrin ML, Viscardi RM. Pharmacokinetics, safety, and biologic effects of azithromycin in extremely preterm infants at risk for ureaplasma colonization and bronchopulmonary dysplasia. J Clin Pharmacol. 2011 Sep;51(9):1264-75. doi: 10.1177/0091270010382021. Epub 2010 Nov 23.
citation: Viscardi RM, Terrin ML, Magder LS, Davis NL, Dulkerian SJ, Waites KB, Ambalavanan N, Kaufman DA, Donohue P, Tuttle DJ, Weitkamp JH, Hassan HE, Eddington ND. Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2020 Nov;105(6):615-622. doi: 10.1136/archdischild-2019-318122. Epub 2020 Mar 13.