Clinical trial NCT02066129: Step-up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations
Official title: Step-up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Fluticasone
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2014-02-19
Enrollment: 254
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to determine whether, in children receiving low-dose inhaled corticosteroids (ICS), quintupling the dose of inhaled corticosteroids at the onset of symptoms previously associated with upper respiratory illnesses and subsequent asthma exacerbations reduces the rate of severe asthma exacerbations treated with oral corticosteroids.

Detailed description: The study design is a double-blind, parallel-group trial, including a total of 250 participants, ages 5-11 years, with a diagnosis of asthma and a history of at least 1 asthma exacerbation treated with oral corticosteroids in the prior year. All participants will be treated for 48 weeks with open-label fluticasone 44 mcg 2 puffs twice daily. During the 48-week treatment period, participants will receive randomized blinded therapy for 7 days each time they enter the "yellow zone" (at the onset of symptoms previously associated with upper respiratory illnesses and subsequent asthma exacerbations). Yellow zone therapy will be fluticasone 44 or 220 mcg 2 puffs twice daily.

Eligibility criteria: Inclusion Criteria:

* Physician-diagnosed asthma
* At least 1 exacerbation treated with systemic (oral or injectable) corticosteroids in the past 12 months
* Able to perform reproducible spirometry
* Current treatment with step 2 controller therapy \[low-dose ICS, leukotriene receptor antagonist (LTRA)\] OR current treatment with step 3 controller therapy \[low-dose ICS + long-acting beta agonist (LABA), low-dose ICS + LTRA, or medium dose ICS\] with a childhood Asthma Control Test (c-ACT) score of \>19, no more than 2 prednisone treated exacerbations in the past 6 months, prebronchodilator Forced Expiratory Volume at 1 second (FEV1) ≥ 80% predicted and willing to step down therapy OR controller naïve and qualifying for step 2 controller therapy \[asthma symptoms or short acting beta agonist (SABA) use \> 2 days per week or night-time awakenings due to asthma \> 2 nights per month\]
* Prebronchodilator FEV1 ≥ 60% predicted
* Ability and willingness to provide informed assent
* For females of childbearing potential: not pregnant, non-lactating, and agree to practice an adequate birth control method.
* History of clinical varicella or varicella vaccine

Exclusion Criteria:

* Systemic (oral or injectable) corticosteroids within previous 2-week period
* Current or recent (previous 2-weeks) use of medications known to significantly interact with corticosteroid disposition, including but not limited to carbamazepine, erythromycin, phenobarbital, phenytoin, rifampin, and ketoconazole
* Presence of chronic or active lung disease other than asthma
* Significant medical illness other than asthma, including thyroid disease, diabetes mellitus, Cushing's disease, Addison's disease, hepatic disease, or concurrent medical problems that could require oral corticosteroids during the study
* A history of cataracts, glaucoma, or any other medical disorder associated with an adverse effect to corticosteroids
* History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure
* More than 5 prednisone treated exacerbations in the past 12 months
* More than 1 hospitalizations lasting \>24 hours for asthma in the past 12 months
* History of adverse reactions to ICS preparations or any of their ingredients
* Receiving hyposensitization therapy other than an established maintenance regimen (On maintenance regimen for ≥ 3 months)
* History of premature birth before 35 weeks gestation

Primary outcomes:
measure: Asthma Exacerbations
timeFrame: end of 48 week treatment period
Secondary outcomes:
measure: Yellow Zone Asthma Symptoms
timeFrame: end of 48 week treatment period
measure: Yellow Zone Albuterol Use
timeFrame: end of 48 week treatment period
measure: Unscheduled Emergency Department (ED) or Urgent Care Visits for Asthma
timeFrame: end of 48 week treatment period
measure: Number of Participants Hospitalized for Asthma
timeFrame: end of 48 week treatment period
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona College of Medicine
state: Arizona
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center/Stroger Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital
state: Illinois
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital, Case Western Reserve University
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: William Busse, MD
role: STUDY_CHAIR
References:
citation: Jackson DJ, Bacharier LB, Mauger DT, Boehmer S, Beigelman A, Chmiel JF, Fitzpatrick AM, Gaffin JM, Morgan WJ, Peters SP, Phipatanakul W, Sheehan WJ, Cabana MD, Holguin F, Martinez FD, Pongracic JA, Baxi SN, Benson M, Blake K, Covar R, Gentile DA, Israel E, Krishnan JA, Kumar HV, Lang JE, Lazarus SC, Lima JJ, Long D, Ly N, Marbin J, Moy JN, Myers RE, Olin JT, Raissy HH, Robison RG, Ross K, Sorkness CA, Lemanske RF Jr; National Heart, Lung, and Blood Institute AsthmaNet. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations. N Engl J Med. 2018 Mar 8;378(10):891-901. doi: 10.1056/NEJMoa1710988. Epub 2018 Mar 3.