Please select the eligibility criteria that correspond to the clinical trial below.
Title: BALLOON: Efficacy and Safety - Study by ALTANA on Ciclesonide in Pre-school Asthma Patients
Brief Summary: The aim of the present study is to compare the efficacy of inhaled ciclesonide in pre-school children. Ciclesonide will be inhaled once daily, using one of three dose levels and tested versus placebo. The study duration consists of a baseline period (2 to 4 weeks) and a treatment period (24 weeks). The study will provide further data on safety and tolerability of ciclesonide.


Options:
A: Main Inclusion Criteria:

* Written informed consent by the parents or legal guardians of the patient
* Outpatients
* Good health with the exception of asthma
* Documented diagnosis of asthma for more than 6 months
* Use of rescue medication only or pretreatment with a controller drug

Main Exclusion Criteria:

* Concomitant severe diseases
* Diseases contraindicated for the use of inhaled steroids
* Other relevant lung diseases causing impairment in pulmonary function
* Recurrent, episodic wheezing only
* History of life-threatening asthma
* History of any mechanical ventilation
* Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation
* Premature birth (\< 32 weeks gestation)
B: Inclusion Criteria:

* (1) Children aged 1-6 years,
* (2) they had at least 2 documented episodes of URTI-induced asthma requiring systemic (i.e., oral, intravenous, or intramuscular) corticosteroids in the previous 12 months or 1 episode in the previous 6 months,
* (3) no intercurrent symptoms (i.e., cough, wheezing, or observed dyspnea) documented for at least 7 days between wheezing episodes,
* (4) no suspicion of allergy to pollen or perennial allergens, and
* (5) caregivers have a good understanding of French or English

Exclusion Criteria:

* (a) other chronic diseases such as cystic fibrosis, bronchopulmonary dysplasia, cardiac disease, kidney disease, gastro-oesophageal reflux requiring treatment,
* (b) intake, in the 21 days preceding randomization, of inhaled, nasal, or oral corticosteroids, leukotriene antagonists, cromolyn, nedocromyl, or ketotifen, -(c) prior intubation for an asthma exacerbation.
C: Inclusion Criteria:

* Able to perform reproducible spirometry according to American Thoracic Society (ATS) criteria
* History of asthma symptoms that are adequately controlled in the 4 weeks prior to study entry, and meets at least one of the following criteria:

  1. History of mild persistent asthma symptoms (on average greater than 2 days per week with symptoms or albuterol use for symptoms or greater than 2 night-time awakenings per month during the year prior to study entry) and has been treated with a single-controller inhaled corticosteroid (ICS) dose less than or equal to 160 mcg per day of a beclomethasone-equivalent or a leukotriene receptor antagonist (LTRA) (in an age-appropriate dose) for the 4 weeks prior to study entry; individuals treated with a combination controller therapy (e.g. ICS+LTRA or ICS+long-acting beta-agonist (LABA)) in the past 8 weeks will not be eligible
  2. Not currently being treated with ICS, a history of mild persistent asthma, and 1 to 2 exacerbations in the year prior to study entry (but none in the 3 months prior to study entry)
* Forced expiratory volume in one second (FEV1) reversibility of greater than or equal to 12% following bronchodilator administration (4 puffs); individuals who do not meet this requirement may qualify for enrollment if their methacholine provocative concentration at 20% (PC20) is less than or equal to 12.5 milligrams per milliliter (mg/ml)
* History of clinical varicella or varicella vaccine; individuals needing the vaccine may receive it from their primary care physician prior to study entry
* Ability of parent to provide informed consent; verbal assent must be obtained from children less than 7 years of age and written assent must be obtained from children between 7 and 18 years of age
* If female, willing to use an effective form of contraception

Participants will be eligible for the 44 weeks of treatment if, after the 4-week screening period, their asthma remains controlled, and they demonstrate at least 80% predicted pre-bronchodilator FEV1. Participants must meet ALL of the criteria stated below during the 8-week screening period to continue in the study:

* Meets the definition of acceptable asthma control, which is NOT having one or more of the following during ANY 2-week period:

  1. On average, on more than 2 days per week, experiences one or more of the following:

     1. Diary-reported symptoms
     2. The use of inhaled bronchodilator (not including pre-exercise)
     3. Peak flows in the yellow zone (less than 80% of personal best defined as based on peak expiratory flow (PEF) value obtained at study visit 1
  2. More than 1 night-time awakening due to asthma
* Demonstrates adherence with taking study medications (at least 75% of scheduled doses), rescue medications (using both rescue inhalers for at least 75% of rescue doses), and completing patient diaries (at least 75% of days)
* Pre-bronchodilator FEV1 greater than or equal to 80% predicted at study visits 2 and 3
* Agrees to not use a spacer with beclomethasone/placebo study and rescue medications

NOTE: In January 2008, the Data and Safety Monitoring Board (DSMB) approved changes in the TREXA eligibility criteria, by which neither FEV1 reversibility ≥ 12% nor a participant's methacholine PC20 ≤ 12.5 mg/ml were required for randomization.

Exclusion Criteria:

* Corticosteroid treatment for any condition prior to study entry within the following defined timepoints:

  1. Oral - Use within 2-week period of the screening visit
  2. Injectable - Use within 2-week period of the screening visit
  3. Nasal corticosteroids may be used at any time during the study at the discretion of the study investigator or primary care physician
* Current or prior use of medications known to significantly interact with corticosteroid disposition (within a 2-week period of study visit 1), including but not limited to carbamazepine, erythromycin or other macrolide antibiotics, phenobarbital, phenytoin, rifampin, or ketoconazole
* Pre-bronchodilator FEV1 less than 60% predicted at study visit 1
* Any hospitalization for asthma in the year prior to study entry
* 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
* History of cataracts, glaucoma, or any other medical disorder associated with an adverse effect to corticosteroids
* Any asthma exacerbation in the past 3 months or more than 2 in the past year.
* History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure
* History of adverse reactions to ICS preparations or any of its ingredients
* Receiving hyposensitization therapy other than an established maintenance regimen (continuous regimen for at least 3 months)
* Pregnant or breastfeeding
* Cigarette smoking or smokeless tobacco use in the year prior to study entry
* Refusal to consent to a genotype evaluation
* Current participation or participation within 1 month of study entry in another investigational drug trial
* Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before study completion
D: Inclusion Criteria:

* Able to perform reproducible spirometry according to American Thoracic Society (ATS) criteria
* History of asthma symptoms (e.g., cough, wheezing, shortness of breath) and meets at least one of the following criteria:

  1. Naïve to controller therapy and meeting National Asthma Education and Prevention Program (NAEPP) criteria for mild-moderate persistent asthma (symptoms at least 2 days per week and/or night-time awakenings due to asthma at least 2 nights per month)
  2. Current uncontrolled asthma (meets NAEPP criteria for mild-moderate persistent asthma) while receiving an ICS dose greater than or equal to 200 ug per day of fluticasone equivalent or some form of non-ICS controller therapy (e.g., montelukast, theophylline, cromolyn)
  3. Asthma is currently under control while receiving an ICS dose between 300 to 400 ug per day of fluticasone equivalent and willing to consider changing current treatment to monotherapy with one dose of ICS (current standard of care)
  4. Asthma is currently under control while receiving some form of combination therapy, such as ICS less than or equal to 200 ug per day of fluticasone equivalent in addition to a non-ICS controller therapy (e.g., LABA, montelukast, theophylline, cromolyn), and willing to consider changing current treatment to monotherapy with one dose of ICS (current standard of care)
* FEV1 reversibility of at least 12% following bronchodilator administration (4 puffs) at study visit 1. Individuals will need to hold albuterol, montelukast, theophylline, ipratropium bromide (or other anticholinergics) and LABAs per study instructions prior to reversibility testing. If an individual is receiving these types of medications prior to study visit 1, he/she may be brought back to the clinical center within 1 week following appropriate medication withholding to attempt qualification by reversibility criteria. If the individual does not meet this requirement, they may qualify for enrollment if their PC20 methacholine FEV1 is less than or equal to 12.5 mg/ml at the time of randomization. If FEV1 is less than 70%, thus precluding the methacholine challenge at this visit, then completion of the visit will be postponed several days and an additional attempt to obtain a methacholine challenge test will be made. If the methacholine challenge still cannot be performed, an individual may still qualify by reversibility criteria at this visit.
* History of clinical varicella or varicella vaccine; individuals needing the vaccine may receive it from their primary care physician prior to study entry
* Ability of parent to provide informed consent; verbal assent must be obtained from children less than 7 years of age and written assent must be obtained from children between 7 and 18 years of age
* If female, willing to use an effective form of contraception

Prior to being randomly assigned to a treatment group, participants must meet the following criteria to remain in the study:

* Lack of acceptable asthma control during the 8-week screening period as defined by the following criteria:

  1) On average, on more than 2 days per week, one or all of the following:
  1. Diary-reported symptoms
  2. The use of inhaled bronchodilator (not including pre-exercise)
  3. Peak flows in the yellow zone (less than 80% of post bronchodilator PEF value obtained at study visit 1) OR
* On average, more than 1 night-time awakening due to asthma, during each 2-week period

Exclusion Criteria:

* Corticosteroid treatment for any condition prior to study entry within the following defined timepoints:

  1. Oral - Use within 2 weeks of the screening visit
  2. Injectable - Use within 2 weeks of the screening visit
  3. Nasal - May be used at any time during the study at the discretion of the study investigator or primary care physician
* Current or prior use of medications known to significantly interact with corticosteroid disposition (within a 2-week period of study visit 1), including but not limited to carbamazepine, erythromycin or other macrolide antibiotics, phenobarbital, phenytoin, rifampin, or ketoconazole
* Pre-bronchodilator FEV1 less than 60% predicted at study visit 1
* More than three hospitalizations for asthma in the year prior to study entry
* 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 or would place the participant at increased risk while participating in the study
* History of cataracts, glaucoma, or any other medical disorder associated with an adverse effect to corticosteroids
* Gastroesophageal reflux symptoms not controlled by standard medical therapy
* History of significant asthma exacerbation within 2 weeks of study visit 1 or more than 5 courses of systemic corticosteroids in the year prior to study entry
* History of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure within the 5 years prior to study entry
* History of adverse reactions to ICS, LTRA, or LABA preparations or any of their ingredients
* Receiving hyposensitization therapy other than an established maintenance regimen (i.e., continuous regimen for at least 3 months prior to study entry)
* Pregnant or breastfeeding
* Inability to perform study procedures
* Refusal to consent to a genotype evaluation
* Inability of the child to ingest the study drug
* Cigarette smoking or smokeless tobacco use in the year prior to study entry
* Current participation or participation in the month prior to study entry in another investigational drug trial
* Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before study completion

Answer: A