Overview

This trial is active, not recruiting.

Conditions asthma, wheezing
Treatments azithromycin, prednisolone, placebo azithromycin, placebo prednisolone
Phase phase 3
Sponsor Milton S. Hershey Medical Center
Collaborator National Heart, Lung, and Blood Institute (NHLBI)
Start date March 2011
End date September 2014
Trial size 600 participants
Trial identifier NCT01272635, 1U10HL098115, AsthmaNet 002

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
azithromycin
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
prednisolone
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
(Experimental)
azithromycin
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
placebo prednisolone
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
(Experimental)
prednisolone
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
placebo azithromycin
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
(Placebo Comparator)
placebo azithromycin
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
placebo prednisolone
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day

Primary Outcomes

Measure
APRIL: progression to clinically significant lower respiratory tract symptoms
time frame: 14 days after initiation of APRIL therapy
OCELOT: Pediatric Respiratory Assessment Measure
time frame: 36-72 hours after initiation of OCELOT therapy

Secondary Outcomes

Measure
asthma related symptoms
time frame: 14 days after initiation of therapy
absence from school, daycare, and/or parental work
time frame: 14 days after initiation of therapy
urgent care visits, ED visits and hospitalizations
time frame: 14 days after initiation of therapy
drug related side effects
time frame: 14 days after initiation of therapy

Eligibility Criteria

Male or female participants from 12 months up to 71 months old.

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.

Additional Information

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
Principal investigator Leonard B Bacharier, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2013.
Information provided to ClinicalTrials.gov by Milton S. Hershey Medical Center.