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

NCT ID: NCT01272635

Last Updated: 2016-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 607 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2015-01-31

Brief 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.

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.

Conditions

Asthma; Wheezing

Keywords

Asthma; Wheezing; Respiratory Tract Illness; Azythromycin; Prednisolone; Preschool-age

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Azythromycin (APRIL) and Prednisolone (OCELOT)

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day

Prednisolone

Intervention Type: DRUG

Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day

Azythromycin (APRIL) and Placebo (OCELOT)

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day

Placebo Prednisolone

Intervention Type: DRUG

Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day

Placebo (APRIL) and Prednisolone (OCELOT)

Group Type: EXPERIMENTAL

Prednisolone

Intervention Type: DRUG

Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day

Placebo Azithromycin

Intervention Type: OTHER

Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day

Placebo (APRIL) and Placebo (OCELOT)

Group Type: PLACEBO_COMPARATOR

Placebo Azithromycin

Intervention Type: OTHER

Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day

Placebo Prednisolone

Intervention Type: DRUG

Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day

Interventions

Azithromycin

Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day

Intervention Type: DRUG

Prednisolone

Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day

Intervention Type: DRUG

Placebo Azithromycin

Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day

Intervention Type: OTHER

Placebo Prednisolone

Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day

Intervention Type: DRUG

Eligibility 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

• >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.

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 71 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

dave mauger

Principal Investigator, AsthmaNet Data Coordinating Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William B Busse, MD

Role: STUDY_CHAIR

University of Wisconsin, Madison

Leonard B Bacharier, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Fernando D Martinez, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

David T Mauger, PhD

Role: PRINCIPAL_INVESTIGATOR

Penn State University

Robert F Lemanske, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Wanda Phipatanakul, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Jacqueline Pongracic, MD

Role: PRINCIPAL_INVESTIGATOR

Ann & Robert H Lurie Children's Hospital of Chicago

David Gozal, MD

Role: PRINCIPAL_INVESTIGATOR

Comer Children's Hospital

James Moy, MD

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center

Stanley Szefler, MD

Role: PRINCIPAL_INVESTIGATOR

National Jewish Health

Hengameh Raissy, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of New Mexico

Elizabeth Bade, MD

Role: PRINCIPAL_INVESTIGATOR

Aurora Sinai Medical Center

Fernando Holguin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

James Chmiel, MD

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University School of Medicine

Michael Cabana, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Mindy Benson, PNP

Role: PRINCIPAL_INVESTIGATOR

UCSF Benioff Children's Hospital Oakland

W. Gerald Teague, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia Health System

Anne Fitzpatrick, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

University of Arizona College of Medicine

Tucson, Arizona, United States

Children's Hospital & Research Center Oakland

Oakland, California, United States

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

University of New Mexico

Albuquerque, New Mexico, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

University of Virginia Health System

Charlottesville, Virginia, United States

University of Wisconsin

Madison, Wisconsin, United States

Center for Urban Population Health

Milwaukee, Wisconsin, United States

Countries

United States

References

Fitzpatrick AM, Grunwell JR, Cottrill KA, Mutic AD, Mauger DT. Blood Eosinophils for Prediction of Exacerbation in Preschool Children With Recurrent Wheezing. J Allergy Clin Immunol Pract. 2023 May;11(5):1485-1493.e8. doi: 10.1016/j.jaip.2023.01.037. Epub 2023 Feb 3.

Reference Type: DERIVED

PMID: 36738927 (View on PubMed)

Bacharier LB, Guilbert TW, Mauger DT, Boehmer S, Beigelman A, Fitzpatrick AM, Jackson DJ, Baxi SN, Benson M, Burnham CD, Cabana M, Castro M, Chmiel JF, Covar R, Daines M, Gaffin JM, Gentile DA, Holguin F, Israel E, Kelly HW, Lazarus SC, Lemanske RF Jr, Ly N, Meade K, Morgan W, Moy J, Olin T, Peters SP, Phipatanakul W, Pongracic JA, Raissy HH, Ross K, Sheehan WJ, Sorkness C, Szefler SJ, Teague WG, Thyne S, Martinez FD. Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial. JAMA. 2015 Nov 17;314(19):2034-2044. doi: 10.1001/jama.2015.13896.

Reference Type: DERIVED

PMID: 26575060 (View on PubMed)

Other Identifiers

1U10HL098115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AsthmaNet 002

Identifier Type: -

Identifier Source: org_study_id