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

NCT01272635 | Completed Phase 3 Results DMC

• 2 other identifiers: AsthmaNet 0021U10HL098115
• Study Type: interventional
• Target: 607
• Locations: 1 country
• Sites: 16

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.

Conditions

Asthma; Wheezing

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  36-72 hours after initiation of OCELOT therapy

Secondary Outcomes (4)

• Asthma Related Symptoms Among RTI Progressing to Severe LRTI

  14 days after initiation of therapy

• Absence From School, Daycare, and/or Parental Work

  14 days after initiation of therapy

• Urgent Care Visits, ED Visits and Hospitalizations

  14 days after initiation of therapy

• Drug Related Side Effects

  14 days after initiation of therapy

Study Arms (4)

Azythromycin (APRIL) and Prednisolone (OCELOT)

EXPERIMENTAL

Drug: Azithromycin; Drug: Prednisolone

Azythromycin (APRIL) and Placebo (OCELOT)

EXPERIMENTAL

Drug: Azithromycin; Drug: Placebo Prednisolone

Placebo (APRIL) and Prednisolone (OCELOT)

EXPERIMENTAL

Drug: Prednisolone; Other: Placebo Azithromycin

Placebo (APRIL) and Placebo (OCELOT)

PLACEBO COMPARATOR

Other: Placebo Azithromycin; Drug: Placebo Prednisolone

Interventions

Azithromycin DRUG

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

Azythromycin (APRIL) and Placebo (OCELOT); Azythromycin (APRIL) and Prednisolone (OCELOT)

Prednisolone DRUG

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

Azythromycin (APRIL) and Prednisolone (OCELOT); Placebo (APRIL) and Prednisolone (OCELOT)

Placebo Azithromycin OTHER

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

Placebo (APRIL) and Placebo (OCELOT); Placebo (APRIL) and Prednisolone (OCELOT)

Placebo Prednisolone DRUG

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

Azythromycin (APRIL) and Placebo (OCELOT); Placebo (APRIL) and Placebo (OCELOT)

Eligibility Criteria

• Age: 12 Months - 71 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• \>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:

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (16)

University of Arizona College of Medicine

Tucson, Arizona, 85724, United States

Location

Children's Hospital & Research Center Oakland

Oakland, California, 94609, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94143, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin

Madison, Wisconsin, 53972, United States

Location

Center for Urban Population Health

Milwaukee, Wisconsin, 53223, United States

Location

Related Publications (2)

• 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.

  PMID: 36738927 DERIVED

• 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.

  PMID: 26575060 DERIVED

MeSH Terms

Conditions

Asthma; Respiratory Sounds

Interventions

Azithromycin; Prednisolone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: David Mauger
• Organization: Penn State University

dtm5@psu.edu

717-531-7178

Study Officials

• William B Busse, MD

  University of Wisconsin, Madison

  STUDY CHAIR

• 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

  Boston Children's Hospital

  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

  University of Pittsburgh

  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

  UCSF Benioff Children's Hospital Oakland

  PRINCIPAL INVESTIGATOR

• W. Gerald Teague, MD

  University of Virginia Health System

  PRINCIPAL INVESTIGATOR

• Anne Fitzpatrick, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, AsthmaNet Data Coordinating Center

Study Record Dates

• First Submitted: January 7, 2011
• First Posted: January 10, 2011
• Study Start: March 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: December 28, 2016
• Results First Posted: December 28, 2016

Record last verified: 2016-11

Locations

US (16)