Treatment of Preschool Children With Upper Respiratory Tract Illnesses Using Azythromycin and Lower Respiratory Tract Symptoms Using Oral Corticosteroids.

Asthma Clinical Trial

— APRIL - OCELOT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01272635
• Other study ID #: AsthmaNet 002
• Secondary ID: 1U10HL098115
• Status: Completed
• Phase: Phase 3
• First received: January 7, 2011
• Last updated: January 9, 2015
• Start date: March 2011
• Est. completion date: January 2015

Study information

• Verified date: January 2015
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 607
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Months to 71 Months

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma
• Wheezing

Intervention

Drug:
• 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

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

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Emory University	Atlanta	Georgia
United States	Children's Hospital Boston	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	National Jewish Health	Denver	Colorado
United States	University of Wisconsin	Madison	Wisconsin
United States	Center for Urban Population Health	Milwaukee	Wisconsin
United States	Children's Hospital & Research Center Oakland	Oakland	California
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	UCSF Benioff Children's Hospital	San Francisco	California
United States	St. Louis Children's Hospital	St. Louis	Missouri
United States	University of Arizona College of Medicine	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	APRIL: progression to clinically significant lower respiratory tract symptoms		14 days after initiation of APRIL therapy	No
Primary	OCELOT: Pediatric Respiratory Assessment Measure		36-72 hours after initiation of OCELOT therapy	No
Secondary	asthma related symptoms		14 days after initiation of therapy	No
Secondary	absence from school, daycare, and/or parental work		14 days after initiation of therapy	No
Secondary	urgent care visits, ED visits and hospitalizations		14 days after initiation of therapy	No
Secondary	drug related side effects		14 days after initiation of therapy	No