Please select the eligibility criteria that correspond to the clinical trial below.
Title: Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations (ICAC-20)
Brief Summary: The purpose of this trial is to compare the efficacy of 4 to 5 months of three treatments - omalizumab, corticosteroid therapy boost, and placebo - in reducing fall exacerbations in inner-city children and adolescents with allergic persistent asthma when initiated approximately 4 -6 weeks prior to the start of the first day of each participant's school year.


Options:
A: Inclusion Criteria:

* Male and female non-smoking Participants, ages 6 to 14 years, with chronic asthma, history of at least one asthma exacerbation associated with a cold within the past year and a documented history of asthma that required treatment with any asthma medication within 6 months prior to Visit 1

Exclusion Criteria:

* Participant cannot have any other acute or chronic pulmonary disorder, or hospitalization for asthma more than three times within one year prior to signing informed consent
B: Inclusion Criteria:

* Diagnosed with asthma
* Enrolled in a participating elementary school
C: Inclusion Criteria :

* Combined body weight (as measured at the screening visit) and total serum IgE level (as measured within 3 months of the screening visit) suitable for omalizumab (Xolair®) dosing;
* A diagnosis of asthma by a clinician made more than 1 year prior to recruitment; participants who received an asthma diagnosis by a clinician less than 1 year prior to recruitment must report that their respiratory symptoms were present for more than 1 year prior to recruitment;
* Having a requirement for at least 100 mcg fluticasone 100 mcg twice a day or equivalent at the Assumption of Care Visit AND who meet at least one of the following criteria:

  i. ≥1 asthma-related exacerbations, separated by at least two weeks, requiring treatment with a systemic corticosteroid course in the previous 12 months ii. ≥1 asthma-related overnight hospitalizations in the past 12 months.
* A positive prick skin-test to at least one perennial allergen (i.e. dust mite, cockroach, mold, cat, dog, rat, mouse) documented at the screening visit or at a ICAC study visit within 12 months of the screening visit;
* Primary place of residence is in one of the pre-selected recruitment census tracts;
* Able to perform spirometry;
* Parent or legal guardian is willing to sign the written informed consent (age appropriate) prior to initiation of any study procedure;
* Willing to sign the assent form, if age appropriate;
* A history of chickenpox or receipt of the chickenpox vaccine;
* Insurance which covers costs of medications; and
* Have not used and do not plan to restart any of the following medications in the 7 days prior to the first visit: tricyclic antidepressants, ketaconazole, or beta adrenergic blocker drugs (oral and/or topical).

Exclusion Criteria:

Participants who meet any of the following criteria are not eligible for enrollment but may be reassessed:

* Assigned to a treatment of less than 100 mcg fluticasone twice a day or equivalent at the Assumption of Care Visit;
* Pregnant or lactating. Females of child-bearing potential (post-menarche) must be abstinent or use a medically acceptable birth control method throughout the study (e.g. oral, subcutaneous, mechanical, or surgical contraception);
* Clinically significant laboratory abnormalities (not associated with the study indication) at the screening visit;
* Platelet count less than 100 x 10\^9/L at the screening visit;
* Currently participating in another asthma-related pharmaceutical study or intervention study or who have participated in another asthma-related pharmaceutical study or intervention study in the month prior to Recruitment;
* Living with a foster parent: exception -not applicable if participant is able to provide consent;
* Does not have access to a phone (needed for scheduling appointments);
* Plan(s) to move from the area during the study period;
* Has previously been treated with omalizumab (Xolair®) within 1 year of recruitment;
* Currently receiving or has received hyposensitization therapy to any allergen in the past year prior to recruitment;
* Has received hyposensitization therapy to dust mite, Alternaria or cockroach for ≥ 6 months in the past 3 years prior to Recruitment;
* Has experienced a life-threatening asthma exacerbation in the last 2 years requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure;
* Home-schooled or in year round school;
* Are currently taking or who have taken any of the following medications within 4 weeks of the Screening Visit: monoamine oxidase inhibitors (phenelzine, tranylcypromine); tricyclic and tetracyclic antidepressants; beta adrenergic blocker drugs (both oral and topical); anticonvulsants(carbamazepine, phenobarbital, phenytoin, mephobarbital, primidone,ethosuximide, methsuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, valproic acid, divalproex sodium, zonisamide); protease inhibitors(ritonavir, indinavir, nelfinavir); calcium channel blockers (verapamil, diltiazem); modafinil; tamoxifen; non-nucleoside reverse transcriptase inhibitors; macrolide antibiotics\*(erythromycin, clarithromycin, dirithromycin, troleandomycin); chloramphenicol; nefazodone; aprepitant; St. John's Wort (hypericum); Rifampin\*; Azole antifungals\* (ketoconazole, fluconazole,itraconazole); Sibutramine\*; bergamottin\* (constituent of grapefruit juice).\*may be rescreened if this therapy is short-lived;
* Will not allow the study clinician, an asthma specialist, to manage their disease for the duration of the study or who are not willing to change their asthma medications to follow the protocol.

Participants who meet any of the following criteria are not eligible for assumption of care and may not be reassessed except where noted:

* A current severe hypersensitivity to milk;
* Individuals who were enrolled in the previous ICAC trial, Inner-City Anti-IgE Therapy for Asthma (ICATA,ICAC-NCT00377572);
* Individuals who have any medical illnesses that in the opinion of the investigators would a.) increase the risk the subject would incur by participating in the study; b.) interfere with the measured outcomes of the study; or c.) interfere with the performance of the study procedures. Examples of such diseases are: cystic fibrosis, bronchiectasis, type 1 diabetes, hemophilia, Von Willebrand disease, sickle cell disease, cerebral palsy, rheumatoid arthritis, lupus, psoriasis, hyperimmunoglobulin E syndrome, parasite infections, Wiskott-Aldrich Syndrome or allergic bronchopulmonary aspergillosis.
* Known hypersensitivity to any ingredients, including excipients (sucrose, histidine, polysorbate 20) of the study medication or drugs related to omalizumab (e.g. monoclonal antibodies, polyclonal gamma globulin) or fluticasone;
* Currently have diagnosed cancer, are currently being investigated for possible cancer, or who have a history of cancer;
* Do not primarily speak English (or Spanish at centers with Spanish speaking staff)
* The participant's caretaker does not primarily speak English (or Spanish at centers with Spanish speaking staff); not applicable if participant is able to provide consent.
* A history of severe(grade 3) anaphylactoid or anaphylactic reaction(s).
D: Inclusion Criteria:

* Outpatient
* Subjects must be between the ages of 4 and 11 at Randomization
* Subjects must attend day-care, pre-school, elementary school, or middle school. Day-care attendance is defined as receiving childcare outside the home for at least 10 hours per week. Children who are home-schooled are not eligible for this study. Children on year round and traditional school calendars are eligible for this study.
* Subjects can be randomized into this study at any time between August 2nd, 2010 and August 20th, 2010.
* Males or pre-menarchal females.
* A diagnosis of asthma, as defined by the National Institutes of Health \[NIH, 2007\]
* At Visit 1 subjects must demonstrate a best clinic AM PEF ≥70% of the predicted value \[Polgar, 1971\].
* Each subject must have a history of an exacerbation of asthma between September 1st, 2009 and May 15th, 2010 that required a burst of outpatient systemic corticosteroids (oral or parenteral on \>1 days for worsening symptoms of asthma) or have had an urgent care, hospitalization, or ED visit for asthma during which they received oral/parenteral corticosteroids between September 1st, 2009 and May 15th, 2010.
* Subjects must have prior or current use of controller ICS medication as listed below:
* Subjects who have had prior use of a controller medication consisting of a low dose ICS at any time since September 1st, 2009 are eligible for inclusion in this study (refer to Table 1 for examples of allowed doses of commonly used ICS).
* Subjects currently taking a low dose ICS are eligible for inclusion in the study (refer to Table 1 for examples of allowed doses of commonly used ICS).
* Subjects' currently taking a moderate dose ICS are eligible for inclusion in the study if the subject's asthma has been controlled over the prior 3 months and the subject is a candidate for step down therapy, as defined by current asthma management guidelines \[NIH, 2007\].
* Subjects' currently taking low dose ICS in combination with a LABA are eligible for inclusion in the study if the subject's asthma has been controlled over the prior 3 months and the subject is a candidate for step down therapy, as defined by current asthma management guidelines \[NIH, 2007\].
* All subjects must be able to replace their short-acting beta2-agonists with study-issued albuterol inhalation aerosol at Visit 1 for use as needed for the duration of the study. If a subject demonstrates the inability to coordinate the use of an MDI alone, subjects are permitted to use an Aerochamber Plus spacer. The use or non-use of a spacer for albuterol inhalation aerosol should be consistent for each subject throughout the study. Subjects must be able to withhold inhaled albuterol for at least 6 hours prior to study Visits
* Chickenpox: Reported history of clinical varicella or varicella vaccine. If a subject needs varicella vaccine this will be arranged with a physician and must be received prior to randomization.
* Electronic Peak Flow Meter (ePEF)/Electronic Daily Diary (eDiary): A subject must be able to use the study-provided electronic peak flow meter and the subject/caregiver must be able to enter data using the electronic Diary record.
* Responsibilities of Consenting Parent/Legal Guardian: The subject's parent or legal guardian must commit to assist the subject at a consistent level with administration of investigational product and electronic Diary device and electronic PEF meter throughout the study.
* A subject must demonstrate adequate and appropriate technique for using the DISKUS™ device reliably.
* Fluency in English or USA Spanish: Subject and/or subject's parent/guardian must be able to read, comprehend, and record information in English or USA Spanish.

Exclusion Criteria:

* History of Life Threatening Asthma
* Unstable Asthma
* Concomitant use of corticosteroid medication
* Other Concurrent Diseases/Abnormalities: The known presence of sinus, middle ear, oropharyngeal, upper or lower respiratory tract infections within 4 weeks immediately preceding randomization that required the use of an antibiotic or was accompanied by symptoms of worsening asthma.
* Concomitant Medications: Administration of any other prescription or over the counter medication which would significantly affect the course of asthma, such as omalizumab (Xolair), or interact with sympathomimetic amines, such as: anticonvulsants (barbiturates, hydantoins, carbamazepine), polycyclic antidepressants, beta-adrenergic blocking agents (both cardio-selective and non-selective), phenothiazines,
* Cytochrome P450 3A4 (CYP 3A4) Inhibitors: A subject is not eligible if he/she is receiving a strong CYP 3A4 inhibitor within 4 weeks of Visit 1 (e.g., ritonavir, ketoconazole, itraconazole).
* Immunosuppressive medications: A subject must not be using or require use of immunosuppressive medications (e.g. methotrexate, gold, cyclosporine, azathioprine) during the study.

Note: Immunotherapy for the treatment of allergies is allowed during the study provided it was initiated 4 weeks prior to Visit 1 and the subject remains in the maintenance phase for the duration of the study.

* Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, cystic fibrosis, dyspnea by any cause other than asthma, or other respiratory abnormalities other than asthma.
* Other Concurrent Diseases/Abnormalities: Historical or current evidence of clinically significant uncontrolled disease that in the opinion of the investigator would put the safety of the subject at risk through study participation or would confound the interpretation of the results if the condition/disease exacerbated during the study.

The list of additional excluded conditions/diseases includes, but is not limited to the following:

Uncontrolled hypertension; Uncontrolled hematologic, hepatic, neurologic, or renal disease Uncontrolled gastroesophageal reflux disease, Immunologic compromise, Cardiac arrhythmias, Tuberculosis (current or untreated), Congestive heart failure, Cushing's disease Coronary artery disease, Addison's disease, Current malignancy, Eosinophilic esophagitis Uncontrolled diabetes mellitus, Uncontrolled thyroid disorder

* Severe Hypersensitivity to Milk Proteins: Any immediate hypersensitivity reaction, such as urticaria, angioedema, rash, and bronchospasm to milk proteins
* Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the Dry Powder Inhaler (i.e., lactose).
* Tobacco Use: A history of or present use of any tobacco products.
* Investigational Medications: A subject must not have participated in a study (including a non-interventional study) or used any investigational drug (including devices) within 30 days prior to Visit 1 or within ten half-lives (t1/2) of the prior investigational study (whichever is longer of the two).
* Child in Care: A Child in Care (CiC) is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a CiC can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The determination of whether a child meets the definition of CiC should be made with the study centre staff in consultation with the responsible IRB/Ethics Committee.
* Affiliation with Investigator's Site: A subject is an immediate family member of the participating investigator, sub investigator, study coordinator, or employee of the participating investigator.

Answer: C