Acetaminophen Versus Ibuprofen in Children With Asthma (AVICA)

• ClinicalTrials.gov Identifier: NCT01606319
• Recruitment Status: Completed
• First Posted: May 25, 2012
• Results First Posted: January 16, 2017
• Last Update Posted: January 16, 2017
• Sponsor: Milton S. Hershey Medical Center
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): dave mauger, Milton S. Hershey Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Asthma; Wheezing	Drug: Acetaminophen; Drug: Ibuprofen	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Acetaminophen vs. Ibuprofen in Children With Asthma
• Study Start Date: February 2013
• Actual Primary Completion Date: April 2015
• Actual Study Completion Date: April 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Exacerbation Frequency [ Time Frame: last 46 weeks of 48 week treatment period ]
   the number of asthma exacerbations requiring systemic corticosteroids

Secondary Outcome Measures :

1. Asthma Control Days [ Time Frame: last 46 weeks of 48 week treatment period ]
   proportion of study days on which asthma was controlled, measured by electronic diary
2. Asthma Rescue Medication Use [ Time Frame: last 46 weeks of 48 week treatment period ]
   average albuterol rescue use per week, measured by electronic diary
3. Health Care Utilization [ Time Frame: last 46 weeks of 48 week treatment period ]
   frequency of unscheduled physician visits, emergency department visits or hospitalizations for asthma

Eligibility Criteria

• Ages Eligible for Study: 12 Months to 59 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

University of Arizona College of Medicine

Tucson, Arizona, United States, 85724

United States, California

Children's Hospital & Research Center Oakland

Oakland, California, United States, 94609

UCSF Benioff Children's Hospital

San Francisco, California, United States, 94143

United States, Colorado

National Jewish Health

Denver, Colorado, United States, 80206

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Rush University Medical Center/Stroger Hospital

Chicago, Illinois, United States, 60612

Children's Memorial Hospital

Chicago, Illinois, United States, 60614

United States, Massachusetts

Children's Hospital Boston

Boston, Massachusetts, United States, 02115

Children's Hospital, Boston

Boston, Massachusetts, United States, 02115

United States, Missouri

St. Louis Children's Hospital

St. Louis, Missouri, United States, 63110

United States, North Carolina

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Rainbow Babies and Children's Hospital, Case Western Reserve University

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States, 15224

United States, Virginia

University of Virginia Health System

Charlottesville, Virginia, United States, 22908

United States, Wisconsin

University of Wisconsin-Madison

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Milton S. Hershey Medical Center

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Study Chair: William B Busse, MD; University of Wisconsin, Madison

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: dave mauger, Principal Investigator, AsthmaNet Data Coordinating Center, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT01606319
• Other Study ID Numbers: AsthmaNet 005; 1U10HL098115 ( U.S. NIH Grant/Contract )
• First Posted: May 25, 2012
• Results First Posted: January 16, 2017
• Last Update Posted: January 16, 2017
• Last Verified: November 2016

Keywords provided by dave mauger, Milton S. Hershey Medical Center:

Asthma; Wheezing; Ibuprofen; Acetaminophen; exacerbations; pain; fever

Additional relevant MeSH terms:

Asthma; Respiratory Sounds; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Signs and Symptoms, Respiratory; Acetaminophen; Ibuprofen; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action