Ureaplasma Infections Clinical Trial
— AZIPIIIOfficial title:
A Phase IIb Randomized, Placebo-controlled, Double-blind Trial of Azithromycin to Eradicate Ureaplasma Respiratory Tract Infection in Preterm Infants
| Verified date | November 2020 |
| Source | University of Maryland, Baltimore |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 121 |
| Est. completion date | November 3, 2020 |
| Est. primary completion date | December 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A to 72 Hours |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Johns Hopkins University | Baltimore | Maryland |
| United States | Mercy Medical Center | Baltimore | Maryland |
| United States | University of Maryland School of Medicine | Baltimore | Maryland |
| United States | University of Alabama at Birmingham | Birmingham | Alabama |
| United States | University of Virginia | Charlottesville | Virginia |
| United States | Monroe Carell Jr. Children's Hospital at Vanderbilt | Nashville | Tennessee |
| United States | Christiana Care Health Services | Newark | Delaware |
| Lead Sponsor | Collaborator |
|---|---|
| University of Maryland, Baltimore | Christiana Care Health Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Johns Hopkins University, Mercy Medical Center, University of Alabama at Birmingham, University of Virginia |
United States,
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Number of Participants With Threshold Retinopathy of Prematurity (ROP) | Threshold ROP requiring surgical intervention as diagnosed by ophthalmologic examination | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Other | Number of Participants With Necrotizing Enterocolitis (NEC) | Necrotizing enterocolitis = Bell Stage II by radiographic and clinical criteria. | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Other | Number of Participants With Infections During the NICU Hospitalization | Culture-confirmed bacterial or fungal infection based on culture from sterile site (blood, cerebral spinal fluid, or urine) | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Other | Number of Participants With Severe Intraventicular Hemorrhage (IVH) | Number of Participants with Grade III or IV IVH confirmed by cranial ultrasound | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Other | Number of Participants With Periventricular Leukomalacia (PVL) | The number of Participants with cranial ultrasound confirmed PVL | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Other | Number of Participants With Patent Ductus Arteriosus (PDA) | Detection of PDA by cardiac echocardiogram with left to right shunting, or clinical evidence of murmur, bounding pulses, and widened pulse pressure. | 14 days | |
| Other | Number of Participants With Cardiac Arrhythmia | Number of Participants with EKG evidence of prolonged QT (QTc > 450 ms) | 3 days | |
| Primary | Number of Participants With Survival And Transfer From NICU With Microbiological Eradication of Ureaplasma | 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). | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Secondary | Number of Participants Who Survived Until 36 Wks Postmenstrual Age With Physiologic Defined Bronchopulmonary Dysplasia (BPD) at 36 Weeks Post Menstrual Age | Number of Participants who survived until 36 wks postmenstrual age with Physiologic defined bronchopulmonary dysplasia (BPD) based on oxygen-saturation monitoring | 36 weeks post menstrual age (one month prior to due date) | |
| Secondary | Number of Participants With Death or Neurodevelopmental Impairment | 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. | 22-26 months | |
| Secondary | Number of Participants With Pulmonary Impairment | Parent report of recurrent wheezing and/or chronic cough | 6-26 months | |
| Secondary | Number of Participants Who Died | Number of Participants who died from any cause | 22-26 months | |
| Secondary | Duration of Positive Pressure Support | Combined number of days receiving mechanical ventilation plus non-invasive modes of positive pressure support. | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Secondary | Duration of Oxygen Supplementation | Cumulative number of days of receipt of supplemental oxygen | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Secondary | Number of Participants Who Experienced Air Leaks | Any pulmonary air leak (pulmonary interstitial emphysema, pneumothorax, pneumomediastinum) confirmed by chest x-ray | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Secondary | Number of Participants Who Received Postnatal Steroids | Receipt of steroid medications (hydrocortisone, dexamethasone) | 36 weeks | |
| Secondary | Number of Participants Who Received Non-Study Antibiotics | Received Non-study antibiotics following study drug intervention period. | Participants will be followed for the duration of hospital stay, an expected average of 10 weeks | |
| Secondary | Pharmacokinetics (PK)/Pharmacodynamics (PD) Modelling of Time Course of Azithromycin Plasma Concentrations | 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. | Study day 1-day 7 |