Treatment of Preschool Children With Upper Respiratory Tract Illnesses Using Azythromycin and Lower Respiratory Tract Symptoms Using Oral Corticosteroids. (APRIL - OCELOT)

November 1, 2016 updated by: dave mauger, Milton S. Hershey Medical Center

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
607

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona College of Medicine
    • California
      • Oakland, California, United States, 94609
        • Children's Hospital & Research Center Oakland
      • San Francisco, California, United States, 94143
        • UCSF Benioff Children's Hospital
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • St. Louis Children's Hospital
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Case Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System
    • Wisconsin
      • Madison, Wisconsin, United States, 53972
        • University of Wisconsin
      • Milwaukee, Wisconsin, United States, 53223
        • Center for Urban Population Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 2 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Azythromycin (APRIL) and Prednisolone (OCELOT)
Drug: Azithromycin
Suspension, 12 mg/kg once daily for 5 days, maximum dose 500mg/day
Drug: Prednisolone
Syrup, 1 mg/kg/dose twice daily for 5 days, maximum dose 60mg/day
Experimental: Azythromycin (APRIL) and Placebo (OCELOT)
Drug: 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
Experimental: Placebo (APRIL) and Prednisolone (OCELOT)
Drug: 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
Placebo Comparator: Placebo (APRIL) and Placebo (OCELOT)
Drug: Placebo 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression to Clinically Significant Lower Respiratory Tract Symptoms
Time Frame: 14 days after initiation of APRIL therapy
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
Time Frame: 36-72 hours after initiation of OCELOT therapy
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Asthma Related Symptoms Among RTI Progressing to Severe LRTI
Time Frame: 14 days after initiation of therapy
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.
14 days after initiation of therapy
Absence From School, Daycare, and/or Parental Work
Time Frame: 14 days after initiation of therapy
14 days after initiation of therapy
Urgent Care Visits, ED Visits and Hospitalizations
Time Frame: 14 days after initiation of therapy
Number of participants who had urgent care visits, ED visits, and/or hospitalizations for respiratory symptoms.
14 days after initiation of therapy
Drug Related Side Effects
Time Frame: 14 days after initiation of therapy
Parent-reported gastrointestinal symptoms during treated RTI.
14 days after initiation of therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Milton S. Hershey Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: William B Busse, MD, University of Wisconsin, Madison
  • Principal Investigator: Leonard B Bacharier, MD, Washington University School of Medicine
  • Principal Investigator: David T Mauger, PhD, Penn State University
  • Principal Investigator: Robert F Lemanske, MD, University of Wisconsin, Madison
  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 7, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 10, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 28, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AsthmaNet 002
  • 1U10HL098115 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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