Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations (ICAC-20)
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 478
- Locations
- 8
- Primary Endpoint
- Occurrence of One or More Asthma Exacerbations (Treatment Steps 2-4)
Study Overview
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.
Detailed Description
While the increase in the prevalence of asthma has abated, levels of asthma morbidity and mortality remain near record highs. An asthma exacerbation is a major factor contributing to morbidity, and even mortality in patients with asthma. Although current approaches to treatment have reduced these risks, asthma exacerbations are major problems for inner-city patients and their families, and prevention of these events continues to be a significant challenge. In children with asthma, there are predictable seasonal epidemics of exacerbations, especially during the fall season, otherwise known as the "September epidemic."
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 6 Years to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
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).
Arms & Interventions
Omalizumab
Participants receive active omalizumab (Xolair®) injections and a placebo Flovent® Diskus® (fluticasone) inhaler. Each participant will receive omalizumab (Xolair®) subcutaneous injections at minimum dose of 0.016 mg/kg/IgE (immunoglobulin E) [IU/mL] every 2 or 4 weeks during the 4-5 months treatment period. In addition, all participants receive standardized specialist asthma care.
Intervention: Omalizumab (Biological)
Omalizumab
Participants receive active omalizumab (Xolair®) injections and a placebo Flovent® Diskus® (fluticasone) inhaler. Each participant will receive omalizumab (Xolair®) subcutaneous injections at minimum dose of 0.016 mg/kg/IgE (immunoglobulin E) [IU/mL] every 2 or 4 weeks during the 4-5 months treatment period. In addition, all participants receive standardized specialist asthma care.
Intervention: Placebo fluticasone (Biological)
Inhaled Corticosteroid Boost Therapy (ICS)
Participants in this group, the Inhaled Corticosteroid (ICS) boost arm, receive active ICS and placebo omalizumab (Xolair®) injections. Self-administered fluticasone (Flovent ® Diskus®) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone will be used. In addition, all participants receive standardized specialist asthma care.
Intervention: Inhaled Corticosteroid Boost Therapy (ICS) (Drug)
Inhaled Corticosteroid Boost Therapy (ICS)
Participants in this group, the Inhaled Corticosteroid (ICS) boost arm, receive active ICS and placebo omalizumab (Xolair®) injections. Self-administered fluticasone (Flovent ® Diskus®) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone will be used. In addition, all participants receive standardized specialist asthma care.
Intervention: Placebo omalizumab (Biological)
Placebo
The placebo group receive placebo omalizumab (Xolair®) injections and placebo Flovent® Diskus® (fluticasone) inhaler. In addition, all participants receive standardized specialist asthma care.
Intervention: Placebo omalizumab (Biological)
Placebo
The placebo group receive placebo omalizumab (Xolair®) injections and placebo Flovent® Diskus® (fluticasone) inhaler. In addition, all participants receive standardized specialist asthma care.
Intervention: Placebo fluticasone (Biological)
Outcomes
Primary Outcomes
Occurrence of One or More Asthma Exacerbations (Treatment Steps 2-4)
Time Frame: 90 Day outcome period
Asthma exacerbation defined as a prescription of a course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day. Odds ratio comparing Inhaled corticosteroid boost therapy (ICS) and Omalizumab arms at Treatment Steps 2-4.
Occurrence of One or More Asthma Exacerbations (All Treatment Steps [Steps 2-5])
Time Frame: 90 Day outcome period
Asthma exacerbation defined as a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥ 20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day. Odds ratio comparing Placebo and Omalizumab arms across all treatment steps (Steps 2-5).
Secondary Outcomes
- Virus-induced Exacerbations as Measured by an Exacerbation That is Associated With a Virus Detected Using the Nasal Mucus Samples(90 Day outcome period)
- Severity of Asthma Symptoms Associated With a Viral Infection:Omalizumab vs. Placebo(90 Day outcome period)
- Number of Exacerbations Evaluated Monthly With Viral Respiratory Infections: Omalizumab vs. Placebo(90 Day outcome period)
- Composite Asthma Severity Index (CASI), Treatment Steps 2-5: Omalizumab vs. Placebo(90 Day outcome period)
- Composite Asthma Severity Index (CASI), Treatment Steps 2-4: Omalizumab vs. ICS(90 Day outcome period)
- Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted, Treatment Steps 2-5:Omalizumab vs. Placebo(90 Day outcome period)
- Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted , Treatment Steps 2-4: Omalizumab vs. ICS(90 Day outcome period)
- Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-5: Omalizumab vs. Placebo(90 Day outcome period)
- Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-4: Omalizumab vs. ICS(90 Day outcome period)
- Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-5: Omalizumab vs. Placebo(90 Day outcome period)
- Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-4: Omalizumab vs. ICS(90 Day outcome period)
- Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-5: Omalizumab vs. Placebo(90 Day outcome period)
- Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-4: Omalizumab vs. ICS(90 Day outcome period)
- Work Disruptions Due to Child's Asthma, Treatment Steps 2-5: Omalizumab vs. Placebo(90 Day outcome period)
- Work Disruptions Due to Child's Asthma, Treatment Steps 2-4: Omalizumab vs. ICS(90 Day outcome period)
- School Absences (Percent), Treatment Steps 2-5:Omalizumab vs. Placebo(90 Day outcome period)
- School Absences (Percent), Treatment Steps 2-4: Omalizumab vs. ICS(90 Day outcome period)
- Percent Adherence to Asthma Medication, Treatment Steps 2-5: Omalizumab vs. Placebo(90 Day outcome period)
- Percent Adherence to Asthma Medication, Treatment Steps 2-4: Omalizumab vs. ICS(90 Day outcome period)
- Comparison of Home Allergen (Cockroach) Exposure and Asthma Exacerbations: Omalizumab Versus Placebo(90 Day outcome period)