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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Maryland
Sponsor:
Collaborators:
Mercy Medical Center
Johns Hopkins University
University of Virginia
University of Alabama at Birmingham
Oregon Health and Science University
Information provided by (Responsible Party):
Rose Viscardi, MD, University of Maryland
ClinicalTrials.gov Identifier:
NCT01778634
First received: January 22, 2013
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Ureaplasma Infections
Drug: Azithromycin
Drug: Placebo (for azithromycin)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIb Randomized, Placebo-controlled, Double-blind Trial of Azithromycin to Eradicate Ureaplasma Respiratory Tract Infection in Preterm Infants

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Survival with microbiological eradication of Ureaplasma [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Physiologic defined bronchopulmonary dysplasia (BPD) at 36 weeks post menstrual age [ Time Frame: 36 weeks post menstrual age (one month prior to due date) ] [ Designated as safety issue: Yes ]
    Physiologic definition of BPD based on oxygen-saturation monitoring

  • Death or Neurodevelopmental impairment [ Time Frame: 22-26 months ] [ Designated as safety issue: Yes ]
    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.

  • Pulmonary impairment [ Time Frame: 6-26 months ] [ Designated as safety issue: Yes ]
    Parent report of recurrent wheezing and/or chronic cough

  • Death [ Time Frame: 22-26 months ] [ Designated as safety issue: Yes ]
    Mortality from any cause

  • Duration of positive pressure support [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    Combined number of days receiving mechanical ventilation plus non-invasive modes of positive pressure support.

  • Duration of oxygen supplementation [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    Receipt of supplemental oxygen

  • Air leaks [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    Any pulmonary air leak (pulmonary interstitial emphysema, pneumothorax, pneumomediastinum) confirmed by chest x-ray

  • Received postnatal steroids [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
    Receipt of steroid medications (hydrocortisone, dexamethasone)

  • Received Non-Study antibiotics [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    Received Non-study antibiotics following study drug intervention period.

  • Pharmacokinetics (PK)/Pharmacodynamics (PD) modelling of time course of azithromycin plasma concentrations [ Time Frame: Study day 1-day 7 ] [ Designated as safety issue: No ]
    Population PK model will be refined with additional plasma concentrations in 15 subjects who receive azithromycin.


Other Outcome Measures:
  • Threshold Retinopathy of Prematurity (ROP) [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    Threshold ROP requiring surgical intervention as diagnosed by ophthalmologic examination

  • Necrotizing enterocolitis (NEC) [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    Necrotizing enterocolitis ≥ Bell Stage II by radiographic and clinical criteria.

  • Infections [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    Culture-confirmed bacterial or fungal infection based on culture from sterile site (blood, cerebral spinal fluid, or urine)

  • Severe Intraventicular hemorrhage (IVH) [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    Grade III or IV IVH confirmed by cranial ultrasound

  • Periventricular leukomalacia (PVL) [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 10 weeks ] [ Designated as safety issue: Yes ]
    Cranial ultrasound confirmed PVL

  • Patent ductus arteriosus (PDA) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Detection of PDA by cardiac echocardiogram with left to right shunting, or clinical evidence of murmur, bounding pulses, and widened pulse pressure.

  • Cardiac arrhythmia [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
    EKG evidence of prolonged QT (QTc > 450 ms)


Estimated Enrollment: 180
Study Start Date: July 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo (5% dextrose)
Placebo
Drug: Placebo (for azithromycin)
Other Name: 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 Name: Zithromax

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

Ages Eligible for Study:   up to 72 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Appropriate size for gestational age (AGA)
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01778634

Contacts
Contact: Rose M Viscardi, M.D. 410-706-1913 rviscard@umaryland.edu
Contact: Michael L Terrin, M.D. 410-706-6139 mterrin@epi.umaryland.edu

Locations
United States, Alabama
University of Alabama at Birmingham Not yet recruiting
Birmingham, Alabama, United States, 35249-7335
Principal Investigator: Namasivayam Ambalavanan, M.D.         
United States, Maryland
Johns Hopkins University Not yet recruiting
Baltimore, Maryland, United States, 21287
Sub-Investigator: Susan Aucott, MD         
Principal Investigator: Pamela Donohue, ScD         
Mercy Medical Center Not yet recruiting
Baltimore, Maryland, United States, 21202
University of Maryland School of Medicine Recruiting
Baltimore, Maryland, United States, 21201
Principal Investigator: Rose M Viscardi, MD         
Sub-Investigator: Michael L Terrin, M.D.         
Sub-Investigator: Laurence S Magder, PhD         
United States, Oregon
Oregon Health Sciences University Not yet recruiting
Portland, Oregon, United States, 97239-3098
Principal Investigator: Robert Schelonka, M.D.         
Sub-Investigator: Cindy McEvoy, M.D.         
United States, Virginia
University of Virginia Not yet recruiting
Charlottesville, Virginia, United States, 22908-0386
Principal Investigator: David A Kaufman, M.D.         
Sponsors and Collaborators
Rose Viscardi, MD
Mercy Medical Center
Johns Hopkins University
University of Virginia
University of Alabama at Birmingham
Oregon Health and Science University
Investigators
Study Chair: Rose M Viscardi, M.D. University of Maryland
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: Robert Schelonka, M.D. Oregon Health and Science University
Principal Investigator: Michael L Terrin, M.D. University of Maryland
Principal Investigator: Susan J Dulkerian, M.D. Mercy Medical Center
  More Information

Publications:
Responsible Party: Rose Viscardi, MD, Professor of Pediatrics, University of Maryland
ClinicalTrials.gov Identifier: NCT01778634     History of Changes
Other Study ID Numbers: HP-00054998, R01HD067126
Study First Received: January 22, 2013
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Maryland:
Ureaplasma parvum
Ureaplasma urealyticum
prematurity
bronchopulmonary dysplasia
azithromycin

Additional relevant MeSH terms:
Communicable Diseases
Infection
Respiratory Tract Infections
Ureaplasma Infections
Bacterial Infections
Gram-Negative Bacterial Infections
Mycoplasmatales Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 21, 2014