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Treatment of Preschool Children With Upper Respiratory Tract Illnesses Using Azythromycin and Lower Respiratory Tract Symptoms Using Oral Corticosteroids. (APRIL - OCELOT)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
dave mauger, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT01272635
First received: January 7, 2011
Last updated: October 11, 2013
Last verified: October 2013
  Purpose

This protocol is comprised of two separate, but linked, clinical trials for treating preschool-aged children with recurrent severe episodes of wheezing. The first study (APRIL) will try to prevent wheezing illness from developing using azithromycin. If a wheezing illness does occur, the second trial (OCELOT) will try to decrease the severity of symptoms using oral corticosteroids.


Condition Intervention Phase
Asthma
Wheezing
Drug: Azithromycin
Drug: Prednisolone
Other: Placebo Azithromycin
Drug: Placebo Prednisolone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Azithromycin for Preventing the Development of Upper Respiratory Tract Illness Into Lower Respiratory Tract Symptoms in Children and Oral Corticosteroids for Treating Episodes of Significant Lower Respiratory Tract Symptoms in Children

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • APRIL: progression to clinically significant lower respiratory tract symptoms [ Time Frame: 14 days after initiation of APRIL therapy ] [ Designated as safety issue: No ]
  • OCELOT: Pediatric Respiratory Assessment Measure [ Time Frame: 36-72 hours after initiation of OCELOT therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • asthma related symptoms [ Time Frame: 14 days after initiation of therapy ] [ Designated as safety issue: No ]
  • absence from school, daycare, and/or parental work [ Time Frame: 14 days after initiation of therapy ] [ Designated as safety issue: No ]
  • urgent care visits, ED visits and hospitalizations [ Time Frame: 14 days after initiation of therapy ] [ Designated as safety issue: No ]
  • drug related side effects [ Time Frame: 14 days after initiation of therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: March 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azythromycin (APRIL) and Prednisolone (OCELOT) Drug: Azithromycin
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Drug: Prednisolone
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
Experimental: Azythromycin (APRIL) and Placebo (OCELOT) Drug: Azithromycin
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Drug: Placebo Prednisolone
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
Experimental: Placebo (APRIL) and Prednisolone (OCELOT) Drug: Prednisolone
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
Other: Placebo Azithromycin
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Placebo Comparator: Placebo (APRIL) and Placebo (OCELOT) Other: Placebo Azithromycin
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Drug: Placebo Prednisolone
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day

Detailed Description:

Preschool aged children often have severe bouts of coughing and/or wheezing that lead to visits to the doctor's office, urgent care, emergency room and often hospitalization. APRIL-OCELOT is a randomized, double-blind, placebo controlled study in 600 preschool children with a history of significant wheezing episodes in the year prior to enrollment. All children enter the APRIL portion of the study, which will compare azithromycin to placebo, given for 5 days during the early signs of an upper respiratory tract illness, for preventing the development of lower respiratory tract symptoms. APRIL is a 78 week study, but participation will end earlier if the child requires a fourth course of APRIL treatment or develops significant lower respiratory tract symptoms. Only those children who develop significant lower respiratory tract symptoms during APRIL will enter the OCELOT portion of the study, which will compare oral corticosteroid to placebo for treating lower respiratory tract symptoms as measured by the Pediatric Respiratory Assessment Measure (PRAM). OCELOT participation will be complete after 14 days. Children may not reenter APRIL after completing OCELOT.

  Eligibility

Ages Eligible for Study:   12 Months to 71 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 12-71 months of age.
  • Recurrent significant wheezing in the past year (any of the following):

    • >3 episodes, ≥1 of which was clinically significant*; OR
    • >2 clinically significant* episodes; OR
    • >4 months of daily controller therapy AND >1 clinically significant* episode.
    • * Clinically significant episode: requiring any of the following: (1) systemic corticosteroids (oral or injectable), (2) unscheduled physician office visit, (3) ED visit, (4) urgent care visit, or (5) hospitalization.
  • Up to date with immunizations, including varicella (unless the subject has already had clinical varicella). If the subject needs varicella vaccine, this will be arranged with the primary care physician and must be received prior to randomization.
  • Willingness to provide informed consent by the child's parent or guardian.

Exclusion Criteria:

Participants who meet any of the following criteria are NOT eligible for enrollment, but may be re-enrolled if these exclusion criteria are resolved:

  • >4 courses of systemic corticosteroids in past 12 months.
  • More than 1 hospitalization for wheezing illnesses within the preceding 12 months.
  • Use of long-term controller medications for asthma, including inhaled corticosteroids, leukotriene modifiers, cromolyn/nedocromil, or theophylline for more than 8 months (cumulative use) in the past 12 months.
  • Current use of higher than step 2 NAEPP asthma guideline therapy (e.g. medium-high dose ICS alone or combination therapy of low-medium-high dose ICS + LABA, montelukast, theophylline or cromolyn). NOTE: children who have evidence of well-controlled symptoms immediately preceding study entry while receiving Step 2 controller therapy (presence of self-reported symptoms on average no more than 2 times per week and less than 2 nights per month of nocturnal awakenings, requiring albuterol, during the 4 weeks preceding visit 1) may be enrolled and will have their controller therapy discontinued upon study entry.
  • Use of OCS in the past 2 weeks.
  • Daily symptoms or >2 nocturnal awakenings, requiring albuterol, on average in the last 2 weeks.
  • Use of antibiotics in the past month.
  • Current treatment with antibiotics for diagnosed sinus disease.
  • Participation presently or in the past month in another investigational drug trial.
  • Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before trial completion.
  • Contraindication of use of systemic corticosteroids or azithromycin.
  • Clinically relevant gastroesophageal reflux.
  • Concurrent medical conditions other than asthma that are likely to require oral or injectable corticosteroids during the study.
  • If receiving allergy shots, change in dose within the past 3 months.

Participants who meet any of the following criteria are NOT eligible for enrollment, and may not be re-enrolled:

  • Gestation less than late preterm as defined as birth before 34 weeks gestational age.
  • Presence of lung disease other than asthma, such as cystic fibrosis and BPD. Evaluation during the screening process will assure that an adequate evaluation of other lung diseases has been performed.
  • Presence of other significant medical illnesses (cardiac, liver, gastrointestinal, endocrine) that would place the study subject at increased risk of participating in the study.
  • Immunodeficiency disorders.
  • History of respiratory failure requiring mechanical ventilation.
  • History of hypoxic seizure.
  • History of significant adverse reaction to any study medication ingredient.
  • The child has significant developmental delay/failure to thrive, defined as crossing of two major percentile lines during the last year for age and gender. If a child plots less than the 10th percentile for age and gender, a growth chart for the previous year will be obtained from the child's primary care provider.
  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: NCT01272635

Locations
United States, Arizona
University of Arizona College of Medicine
Tucson, Arizona, United States, 85724
United States, California
Children's Hospital & Research Center Oakland
Oakland, California, United States, 94609
UCSF Benioff Children's Hospital
San Francisco, California, United States, 94143
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
Rush University Medical Center
Chicago, Illinois, United States, 60612
University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Missouri
St. Louis Children's Hospital
St. Louis, Missouri, United States, 63110
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53972
Center for Urban Population Health
Milwaukee, Wisconsin, United States, 53223
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Study Chair: William B Busse, MD University of Wisconsin, Madison
Principal Investigator: Leonard B Bacharier, MD Washington University School of Medicine
Principal Investigator: Fernando D Martinez, MD University of Arizona
Principal Investigator: David T Mauger, PhD Penn State University
Principal Investigator: Robert F Lemanske, MD University of Wisconsin, Madison
Principal Investigator: Wanda Phipatanakul, MD, MS Children's Hospital Boston
Principal Investigator: Jacqueline Pongracic, MD Ann & Robert H Lurie Children's Hospital of Chicago
Principal Investigator: David Gozal, MD Comer Children's Hospital
Principal Investigator: James Moy, MD Rush University Medical Center
Principal Investigator: Stanley Szefler, MD National Jewish Health
Principal Investigator: Hengameh Raissy, PharmD University of New Mexico
Principal Investigator: Elizabeth Bade, MD Aurora Sinai Medical Center
Principal Investigator: Fernando Holguin, MD Children's Hospital of Pittsburgh of UPMC
Principal Investigator: James Chmiel, MD Case Western Reserve University School of Medicine
Principal Investigator: Michael Cabana, MD, MPH University of California, San Francisco
Principal Investigator: Mindy Benson, PNP Children's Hospital & Research Center Oakland
Principal Investigator: W. Gerald Teague, MD University of Virginia Health System
Principal Investigator: Anne Fitzpatrick, MD Emory University
  More Information

No publications provided

Responsible Party: dave mauger, Principal Investigator, AsthmaNet Data Coordinating Center, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT01272635     History of Changes
Other Study ID Numbers: AsthmaNet 002, 1U10HL098115
Study First Received: January 7, 2011
Last Updated: October 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Milton S. Hershey Medical Center:
Asthma
Wheezing
Respiratory Tract Illness
Azythromycin
Prednisolone
Preschool-age

Additional relevant MeSH terms:
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014