Individualized Therapy For Asthma in Toddlers (INFANT)

Penn State Health

Status and phase: Completed; Phase 3

Conditions: Wheezing; Asthma

Treatments: Drug: as-needed fluticasone propionate; Drug: Montelukast; Drug: daily fluticasone propionate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01606306

1U10HL098115 (U.S. NIH Grant/Contract)

AsthmaNet 004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 300 patients

Sex: All

Ages: 12 to 59 months old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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300 participants in 6 patient groups

Crossover sequence 1

Experimental group

Description:

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

Treatment:

Drug: daily fluticasone propionate

Drug: Montelukast

Drug: as-needed fluticasone propionate

Crossover sequence 2

Experimental group

Description:

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

Treatment:

Drug: daily fluticasone propionate

Drug: Montelukast

Drug: as-needed fluticasone propionate

Crossover sequence 3

Experimental group

Description:

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

Treatment:

Drug: daily fluticasone propionate

Drug: Montelukast

Drug: as-needed fluticasone propionate

Crossover sequence 4

Experimental group

Description:

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

Treatment:

Drug: daily fluticasone propionate

Drug: Montelukast

Drug: as-needed fluticasone propionate

Crossover sequence 5

Experimental group

Description:

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

Treatment:

Drug: daily fluticasone propionate

Drug: Montelukast

Drug: as-needed fluticasone propionate

Crossover sequence 6

Experimental group

Description:

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

Treatment:

Drug: daily fluticasone propionate

Drug: Montelukast

Drug: as-needed fluticasone propionate