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

Phase 2

Completed

• Conditions: Ureaplasma Infections
• Interventions: Drug: Placebo; Drug: Azithromycin

• Registration Number: NCT01778634
• Lead Sponsor: University of Maryland, Baltimore

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).

Study Timeline

• Study First Submitted: 2013-01-22
• Study First Submitted QC: 2013-01-24
• Study First Posted: 2013-01-29
• Study Start: 2013-07
• Primary Completion: 2016-12
• Results First Submitted: 2018-03-02
• Results First Submitted QC: 2018-04-18
• Results First Posted: 2018-05-17
• Status Verified: 2020-11
• Study Completion: 2020-11-03
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 121

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (5% dextrose)	Placebo	Placebo
Azithromycin	Azithromycin	Azithromycin intravenous (2 mg/ml) 20 mg/kg every 24h x 3 days

Primary Outcome Measures

Name	Time	Method
Number of Participants With Survival And Transfer From NICU With Microbiological Eradication of Ureaplasma	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 Outcome Measures

Name	Time	Method
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 who survived until 36 wks postmenstrual age with Physiologic defined bronchopulmonary dysplasia (BPD) based on oxygen-saturation monitoring
Number of Participants With Death or Neurodevelopmental Impairment	22-26 months	Neurodevelopmental impairment will be assigned if any of the following are present at 22-26 months adjusted age: moderate to severe cerebral palsy, bilateral blindness, bilateral hearing impairment requiring amplification, Gross Motor Function Classification System score ≥ 2, or Bayley Scale of Infant and Toddler Development, 3rd edition (BSID-III) cognitive or motor score \<70.
Number of Participants With Pulmonary Impairment	6-26 months	Parent report of recurrent wheezing and/or chronic cough
Number of Participants Who Died	22-26 months	Number of Participants who died from any cause
Duration of Positive Pressure Support	Participants will be followed for the duration of hospital stay, an expected average of 10 weeks	Combined number of days receiving mechanical ventilation plus non-invasive modes of positive pressure support.
Duration of Oxygen Supplementation	Participants will be followed for the duration of hospital stay, an expected average of 10 weeks	Cumulative number of days of receipt of supplemental oxygen
Number of Participants Who Experienced Air Leaks	Participants will be followed for the duration of hospital stay, an expected average of 10 weeks	Any pulmonary air leak (pulmonary interstitial emphysema, pneumothorax, pneumomediastinum) confirmed by chest x-ray
Number of Participants Who Received Postnatal Steroids	36 weeks	Receipt of steroid medications (hydrocortisone, dexamethasone)
Number of Participants Who Received Non-Study Antibiotics	Participants will be followed for the duration of hospital stay, an expected average of 10 weeks	Received Non-study antibiotics following study drug intervention period.
Pharmacokinetics (PK)/Pharmacodynamics (PD) Modelling of Time Course of Azithromycin Plasma Concentrations	Study day 1-day 7	Number of serum azithromycin concentrations that fell outside the 90% prediction interval determined by 200 simulated replicates based on the population PK of azithromycin in preterm infants.

Trial Locations

Locations (7)

Christiana Care Health Services; 🇺🇸 Newark, Delaware, United States

University of Maryland School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Mercy Medical Center; 🇺🇸 Baltimore, Maryland, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt; 🇺🇸 Nashville, Tennessee, United States