Acetaminophen Versus Ibuprofen in Children With Asthma

Study Overview
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Brief Summary
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The Acetaminophen Versus Ibuprofen in Children with Asthma study will test the primary hypothesis that in preschool children 12-59 months of age with persistent asthma on standardized asthma therapy, the number of asthma exacerbations requiring systemic corticosteroids will be more frequent in children randomized to receive acetaminophen as compared to those randomized to receive ibuprofen on an as needed basis for fevers and pain.

Detailed Description
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AVICA is a 48-week randomized therapeutic trial involving two parallel treatment arms: acetaminophen and ibuprofen. Participating children will be randomized to receive either acetaminophen or ibuprofen administered as needed per parental decision for fever and analgesia. This study will address which is the most appropriate antipyretic-analgesic medication in young children with asthma, and will inform both clinicians and parents seeking to treat children with fever and pain. Given the high frequency of administration of these drugs, this study will have a significant impact on pediatric healthcare regardless of whether a differential effect is discovered as significant uncertainty currently exists as to whether acetaminophen use is associated with increased asthma symptoms.

Official Title
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Acetaminophen vs. Ibuprofen in Children With Asthma

Conditions
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Asthma, Wheezing

Intervention / Treatment
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* Drug: Acetaminophen
* Drug: Ibuprofen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 12-59 months of age. If the child is not currently taking long-term asthma controller therapy (meaning that the child has taken no inhaled corticosteroid or leukotriene receptor antagonist medication whatsoever over the past 6 months), then one of the following criteria must be met: Daytime asthma symptoms more than two days per week (average over the past 4 weeks), At least one nighttime awakening from asthma (over the past 4 weeks), Two or more asthma exacerbations requiring systemic corticosteroids in the previous 6 months, Four or more wheezing episodes in the previous 12 months. If the child is currently taking long-term asthma controller therapy (meaning that the child has taken daily or intermittent/as-needed inhaled corticosteroid or leukotriene receptor antagonist over the past 6 months), then one of the following criteria must be met: Taking inhaled corticosteroid or leukotriene receptor antagonist for more than 3 months (or more than 90 days) out of the previous 6 months (or 180 days), Daytime asthma symptoms more than two days per week (average over the past 4 weeks), More than one nighttime awakening from asthma (over the past 4 weeks), Two or more asthma exacerbations requiring systemic corticosteroids in the previous 12 months, Four or more wheezing episodes in the previous 12 months. Up to date with immunizations, including varicella (unless the subject has already had clinical varicella). Willingness to provide informed consent by the child's parent or guardian. Exclusion Criteria: Allergic reaction to the study medications or any component of the study drugs, including (but not limited to) urticaria, rash, angioedema, or hypotension following delivery, Chronic medical disorders that could interfere with drug metabolism/excretion (for instance chronic hepatic, biliary, or renal disease), Chronic medical disorders that may increase the risk of drug-related injury, including (but not limited to): Osteogenesis imperfecta (increased risk of bone demineralization/fracture with corticosteroid therapy), Crohn's disease, ulcerative colitis, juvenile rheumatoid arthritis, clotting disorders, or Factor deficiency (increased risk of bleeding with corticosteroid therapy), G6PD deficiency (increased risk of hemolytic anemia with acetaminophen use), Phenylketonuria (potential for aspartame exposure with study interventions), Seizure disorder treated with anticonvulsants (risk of acetaminophen toxicity with carbamazepine), or History of clotting disorders or Factor deficiency (increased risk of bleeding with corticosteroids), Co-morbid disorders associated with wheezing including (but not limited to) immune deficiency disorders, cystic fibrosis, aspiration, clinically-relevant gastroesophageal reflux, tracheomalacia, congenital airway anomalies (clefts, fistulas, slings, rings), bronchiectasis, bronchopulmonary dysplasia, and/or history of premature birth before 35 weeks gestation, Significant developmental delay/failure to thrive, defined as 5th percentile for height and/or weight or crossing of two major percentile lines during the last year for age and sex, History of a near-fatal asthma exacerbation requiring intubation or assisted ventilation, No primary medical caregiver (e.g., a nurse practitioner, physician assistant, physician, or group medical practice such as a hospital-based clinic) whom the subject can contact for primary medical care, Three or more hospitalizations in the previous 12 months for wheezing or respiratory illnesses, Treatment with 5 or more courses of systemic corticosteroids (oral, intramuscular or intravenous) in the past 6 months, Current use of higher than step 2 NAEPP asthma guideline therapy If receiving allergy shots, change in the dose within the past 3 months.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: acetaminophen<br>acetaminophen given as needed for pain or fever | Drug: Acetaminophen<br>* 15 mg/kg every 6 hours as needed<br>* Other names: paracetamol;|
| Experimental: ibuprofen<br>ibuprofen given as needed for pain or fever | Drug: Ibuprofen<br>* 9.4 mg/kg every 6 hours as needed<br>* Other names: nonsteroidal anti-inflammatory drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exacerbation Frequency | the number of asthma exacerbations requiring systemic corticosteroids | last 46 weeks of 48 week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Control Days | proportion of study days on which asthma was controlled, measured by electronic diary | last 46 weeks of 48 week treatment period | 
| Asthma Rescue Medication Use | average albuterol rescue use per week, measured by electronic diary | last 46 weeks of 48 week treatment period | 
| Health Care Utilization | frequency of unscheduled physician visits, emergency department visits or hospitalizations for asthma | last 46 weeks of 48 week treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Wheezing, Ibuprofen, Acetaminophen, exacerbations, pain, fever