Individualized Therapy For Asthma in Toddlers

NCT ID: NCT01606306

Last Updated: 2017-03-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2015-04-30

Brief Summary

The INFANT study will test whether, in preschool children 12-59 months of age with persistent asthma, the following Step 2 asthma therapies will provide similar degrees of asthma control:

1. Daily inhaled corticosteroid (ICS) treatment,

2. Daily leukotriene receptor antagonist (LTRA) treatment, and

3. As-needed ICS plus short-acting beta agonist (as-needed ICS/SABA) rescue treatment.

Detailed Description

INFANT is a double-blind, randomized clinical trial in which all participants will receive each of the three therapies for 16 weeks by means of a cross-over study design. INFANT aims to determine whether individual children respond better to one treatment than another and, if so, whether those children can be identified by phenotypic characteristics or selected biomarkers. In this regard the INFANT study is expected to address critical gaps in current asthma management guidelines. Ultimately, the findings from this study are expected to help clarify treatment modalities for this population of young preschool children who are extremely difficult to treat.

Conditions

Asthma; Wheezing

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Crossover sequence 1

daily fluticasone propionate, followed by daily montelukast, followed by as needed fluticasone propionate

Group Type: EXPERIMENTAL

daily fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily

Montelukast

Intervention Type: DRUG

Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening

as-needed fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms

Crossover sequence 2

daily fluticasone propionate, followed by as needed fluticasone propionate, followed by daily montelukast

Group Type: EXPERIMENTAL

daily fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily

Montelukast

Intervention Type: DRUG

Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening

as-needed fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms

Crossover sequence 3

daily montelukast, followed by as needed fluticasone propionate, followed by daily fluticasone propionate

Group Type: EXPERIMENTAL

daily fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily

Montelukast

Intervention Type: DRUG

Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening

as-needed fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms

Crossover sequence 4

daily montelukast, followed by daily fluticasone propionate, followed by as needed fluticasone propionate

Group Type: EXPERIMENTAL

daily fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily

Montelukast

Intervention Type: DRUG

Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening

as-needed fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms

Crossover sequence 5

as needed fluticasone propionate, followed by daily fluticasone propionate, followed by daily montelukast

Group Type: EXPERIMENTAL

daily fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily

Montelukast

Intervention Type: DRUG

Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening

as-needed fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms

Crossover sequence 6

as needed fluticasone propionate, followed by daily montelukast, followed by daily fluticasone propionate

Group Type: EXPERIMENTAL

daily fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily

Montelukast

Intervention Type: DRUG

Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening

as-needed fluticasone propionate

Intervention Type: DRUG

Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms

Interventions

daily fluticasone propionate

Flovent® HFA, 44 mcg per inhalation, 2 inhalations twice daily

Intervention Type: DRUG

Montelukast

Singulair®, 4 mg granules or chewable tablets by mouth once daily in the evening

Intervention Type: DRUG

as-needed fluticasone propionate

Flovent® HFA, 44 mcg per inhalation, 2 inhalations, as needed for asthma symptoms

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

dave mauger

Principal Investigator, AsthmaNet Data Coordinating Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William B Busse, MD

Role: STUDY_CHAIR

University of Wisconsin, Madison

Locations

University of Arizona College of Medicine

Tucson, Arizona, United States

Children's Hospital & Research Center Oakland

Oakland, California, United States

UCSF Benioff Children's Hospital

San Francisco, California, United States

National Jewish Health

Denver, Colorado, United States

Emory University

Atlanta, Georgia, United States

Rush University Medical Center/Stroger Hospital

Chicago, Illinois, United States

Children's Memorial Hospital

Chicago, Illinois, United States

Children's Hospital, Boston

Boston, Massachusetts, United States

St. Louis Children's Hospital

St Louis, Missouri, United States

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

Cleveland, Ohio, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

University of Virginia Health System

Charlottesville, Virginia, United States

University of Wisconsin-Madison

Madison, Wisconsin, United States

Countries

United States

References

Fitzpatrick AM, Jackson DJ, Mauger DT, Boehmer SJ, Phipatanakul W, Sheehan WJ, Moy JN, Paul IM, 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 W, Myers RE, Olin JT, Peters SP, Raissy HH, Robison RG, Ross K, Sorkness CA, Thyne SM, Szefler SJ; NIH/NHLBI AsthmaNet. Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol. 2016 Dec;138(6):1608-1618.e12. doi: 10.1016/j.jaci.2016.09.028. Epub 2016 Oct 21.

Reference Type: DERIVED

PMID: 27777180 (View on PubMed)

Other Identifiers

1U10HL098115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AsthmaNet 004

Identifier Type: -

Identifier Source: org_study_id