Acetaminophen Versus Ibuprofen in Children With Asthma (AVICA)

Acetaminophen vs. Ibuprofen in Children With Asthma

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Wheezing
• Intervention / Treatment: Drug: Acetaminophen; Drug: Ibuprofen

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona College of Medicine
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital & Research Center Oakland
    • San Francisco, California, United States, 94143
      • UCSF Benioff Children's Hospital
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center/Stroger Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital, Boston
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Children's Hospital, Case Western Reserve University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: acetaminophen; acetaminophen given as needed for pain or fever	Drug: Acetaminophen; 15 mg/kg every 6 hours as needed; Other Names: tylenol; paracetamol
Experimental: ibuprofen; ibuprofen given as needed for pain or fever	Drug: Ibuprofen; 9.4 mg/kg every 6 hours as needed; Other Names: motrin; advil; nonsteroidal anti-inflammatory drug

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Chair: William B Busse, MD, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Sheehan WJ, Mauger DT, Paul IM, Moy JN, Boehmer SJ, Szefler SJ, Fitzpatrick AM, Jackson DJ, Bacharier LB, Cabana MD, Covar R, Holguin F, Lemanske RF Jr, Martinez FD, Pongracic JA, Beigelman A, Baxi SN, Benson M, Blake K, Chmiel JF, Daines CL, Daines MO, Gaffin JM, Gentile DA, Gower WA, Israel E, Kumar HV, Lang JE, Lazarus SC, Lima JJ, Ly N, Marbin J, Morgan WJ, Myers RE, Olin JT, Peters SP, Raissy HH, Robison RG, Ross K, Sorkness CA, Thyne SM, Wechsler ME, Phipatanakul W; NIH/NHLBI AsthmaNet. Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma. N Engl J Med. 2016 Aug 18;375(7):619-30. doi: 10.1056/NEJMoa1515990.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: May 23, 2012
• First Submitted That Met QC Criteria: May 24, 2012
• First Posted (Estimate): May 25, 2012

Study Record Updates

• Last Update Posted (Estimate): January 16, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: pain; Asthma; exacerbations; fever; Wheezing; Ibuprofen; Acetaminophen
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Respiratory Sounds; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Anti-Inflammatory Agents; Acetaminophen; Ibuprofen; Anti-Inflammatory Agents, Non-Steroidal
• Other Study ID Numbers: AsthmaNet 005; 1U10HL098115 (U.S. NIH Grant/Contract)