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

November 3, 2020 updated by: Rose Viscardi, University of Maryland, Baltimore

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
121

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249-7335
        • University of Alabama at Birmingham
    • Delaware
      • Newark, Delaware, United States, 19713
        • Christiana Care Health Services
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University
      • Baltimore, Maryland, United States, 21201
        • University of Maryland School of Medicine
      • Baltimore, Maryland, United States, 21202
        • Mercy Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232-9544
        • Monroe Carell Jr. Children's Hospital at Vanderbilt
    • Virginia
      • Charlottesville, Virginia, United States, 22908-0386
        • University of Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 hours to 3 days (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo (5% dextrose)
Placebo
Drug: Placebo
D5W
Other Names:
  • equal volume of 5% dextrose water
Experimental: Azithromycin
Azithromycin intravenous (2 mg/ml) 20 mg/kg every 24h x 3 days
Drug: Azithromycin
Azithromycin intravenous 20 mg/kg every 24 h x 3 days
Other Names:
  • Zithromax

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
Participants will be followed for the duration of hospital stay, an expected average of 10 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants Who Survived Until 36 Wks Postmenstrual Age With Physiologic Defined Bronchopulmonary Dysplasia (BPD) at 36 Weeks Post Menstrual Age
Time Frame: 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
36 weeks post menstrual age (one month prior to due date)
Number of Participants With Death or Neurodevelopmental Impairment
Time Frame: 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.
22-26 months
Number of Participants With Pulmonary Impairment
Time Frame: 6-26 months
Parent report of recurrent wheezing and/or chronic cough
6-26 months
Number of Participants Who Died
Time Frame: 22-26 months
Number of Participants who died from any cause
22-26 months
Duration of Positive Pressure Support
Time Frame: 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.
Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Duration of Oxygen Supplementation
Time Frame: 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
Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Number of Participants Who Experienced Air Leaks
Time Frame: 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
Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
Number of Participants Who Received Postnatal Steroids
Time Frame: 36 weeks
Receipt of steroid medications (hydrocortisone, dexamethasone)
36 weeks
Number of Participants Who Received Non-Study Antibiotics
Time Frame: 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.
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
Time Frame: 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.
Study day 1-day 7

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Threshold Retinopathy of Prematurity (ROP)
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
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
Number of Participants With Necrotizing Enterocolitis (NEC)
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
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
Number of Participants With Infections During the NICU Hospitalization
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
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
Number of Participants With Severe Intraventicular Hemorrhage (IVH)
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
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
Number of Participants With Periventricular Leukomalacia (PVL)
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks
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
Number of Participants With Patent Ductus Arteriosus (PDA)
Time Frame: 14 days
Detection of PDA by cardiac echocardiogram with left to right shunting, or clinical evidence of murmur, bounding pulses, and widened pulse pressure.
14 days
Number of Participants With Cardiac Arrhythmia
Time Frame: 3 days
Number of Participants with EKG evidence of prolonged QT (QTc > 450 ms)
3 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Maryland, Baltimore

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Johns Hopkins University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Alabama at Birmingham
Christiana Care Health Services
University of Virginia
Mercy Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Rose M Viscardi, M.D., University of Maryland, College Park
  • Principal Investigator: Pamela Donohue, ScD, Johns Hopkins University
  • Principal Investigator: Namasivayam Ambalavanan, M.D., University of Alabama at Birmingham
  • Principal Investigator: David A Kaufman, M.D., University of Virginia
  • Principal Investigator: Michael L Terrin, M.D., University of Maryland, College Park
  • Principal Investigator: Susan J Dulkerian, M.D., Mercy Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 3, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 22, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 24, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 29, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 30, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 3, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HP-00054998
  • R01HD067126 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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