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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
607
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
University of Arizona College of Medicine
Tucson, Arizona, United States
Children's Hospital & Research Center Oakland
Oakland, California, United States
Progression to Clinically Significant Lower Respiratory Tract Symptoms
Progression to clinically significant lower respiratory tract symptoms defined by: (1) having symptoms that were more than mild after 3 albuterol administrations over 1 hour, or (2) requiring albuterol administrations more often than once every 4 hours, or (3) requiring more than 6 albuterol treatments over a 24-hour period, or (4) having moderate to severe cough or wheeze for 5 or more days since study medication was initiated.
Time frame: 14 days after initiation of APRIL therapy
OCELOT: Pediatric Respiratory Assessment Measure
The Pediatric Respiratory Assessment Measure (PRAM) is a composite outcome with scores ranging from 0-12 with higher numbers representing worse symptoms. The score is calculated as the sum total of the follow five elements: (1) scalene retractions, (2) suprasternal retractions, (3) wheezing, (4) air entry, (5) oxygen saturation. A complete description can be found in: Ducharme FM, Chalut D, Plotnick L, et al. The Pediatric Respiratory Assessment Measure: a valid clinical score for assessing acute asthma severity from toddlers to teenagers. J Pediatr 2008;152:476-80.
Time frame: 36-72 hours after initiation of OCELOT therapy
Asthma Related Symptoms Among RTI Progressing to Severe LRTI
Asthma related symptoms as measured by the parent-completed Pre-school Asthma Symptom Diary (PAD). The PAD was completed daily starting on the first day of an illness and continued until the participant was symptom-free for 2 days. It contains questions of frequency of respiratory symptoms, each scored on a scale of 1 through 7, with higher scores representing increasingly frequent symptoms, with daily scores ranging from 0 (asymptomatic) to a maximum of 102. The total PAD score is the sum of the daily individual symptom scores over the duration of the illness, with higher scores representing more frequent symptoms.
Time frame: 14 days after initiation of therapy
Absence From School, Daycare, and/or Parental Work
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Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
UCSF Benioff Children's Hospital
San Francisco, California, United States
National Jewish Health
Denver, Colorado, United States
Emory University
Atlanta, Georgia, United States
Rush University Medical Center
Chicago, Illinois, United States
Children's Memorial Hospital
Chicago, Illinois, United States
University of Chicago
Chicago, Illinois, United States
Children's Hospital Boston
Boston, Massachusetts, United States
St. Louis Children's Hospital
St Louis, Missouri, United States
...and 6 more locations
Time frame: 14 days after initiation of therapy
Urgent Care Visits, ED Visits and Hospitalizations
Number of participants who had urgent care visits, ED visits, and/or hospitalizations for respiratory symptoms.
Time frame: 14 days after initiation of therapy
Drug Related Side Effects
Parent-reported gastrointestinal symptoms during treated RTI.
Time frame: 14 days after initiation of therapy