CARE Network Maintenance Versus Intermittent Inhaled Steroids in Wheezing Toddlers (MIST)

NCT00675584 | Completed Phase 3 Results DMC

• 7 other identifiers: 5815U10HL0643135U10HL0642885U10HL0643055U10HL0642955U10HL0642875U10HL064307
• Study Type: interventional
• Target: 278
• Locations: 1 country
• Sites: 5

Brief Summary

Asthma affects about 4 million children in the United States and is a leading cause of hospitalizations and school absenteeism. Continuous wheezing in very young children may develop into asthma. Low doses of inhaled corticosteroids (ICS) are commonly prescribed to treat children with particularly bad wheezing episodes. This study will compare the safety and effectiveness of low doses of ICS taken daily versus higher doses of ICS taken only during respiratory tract illnesses for toddlers with continuous wheezing or coughing illnesses.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Rate of Exacerbations Requiring Systemic Corticosteroids

  The rate of exacerbations was calculated as the number of exacerbations requiring prednisone per years of follow-up

  Measured during the 12-month follow-up period

Secondary Outcomes (10)

• Proportion of Episode-free Days

  Measured during the 12-month follow-up period

• Number of Urgent Care Visits, Emergency Department Visits, or Hospitalizations for Wheezing or Asthma Per 12 Months

  Measured during the 12-month follow-up period

• Number of Participants With Treatment Failure

  Measured during the 12-month follow-up period

• Change Between 12 Months and Baseline in Exhaled Nitric Oxide (eNO)

  baseline and 12 months

• Change Between 12 Months and Baseline in Pulmonary Reactance and Resistance Measured Via Oscillometry

  baseline and 12 months

Study Arms (2)

Placebo Budesonide

ACTIVE COMPARATOR

Participants will receive 0.5 mg of ICS (budesonide as Pulmicort Respules®) once a day at night, except during respiratory tract illnesses. During respiratory tract illnesses, participants will receive placebo each morning and 0.5 mg of budesonide each night for 7 days.

Drug: Budesonide; Drug: Placebo Budesonide

Budesonide

EXPERIMENTAL

Participants will receive 1 mg of ICS (budesonide as Pulmicort Respules®) twice a day for 7 days at the onset of a respiratory tract illness; they will receive placebo ICS once a day at all other times during the study.

Drug: Budesonide; Drug: Placebo Budesonide

Interventions

Budesonide DRUG

Participants in Arm 1 will receive 0.5 mg of budesonide once a day. Participants in Arm 2 will receive 1 mg of budesonide twice a day for 7 days at the onset of respiratory tract illnesses.

Also known as: Pulmicort Respules®

Budesonide; Placebo Budesonide

Placebo Budesonide DRUG

Participants in Arm 1 will receive placebo budesonide each morning during respiratory tract illnesses for 7 days. Participants in Arm 2 will receive placebo budesonide once a day for the entire study, other than when they have a respiratory tract illness.

Also known as: Placebo Pulmicort Respules®

Budesonide; Placebo Budesonide

Eligibility Criteria

• Age: 12 Months - 53 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants who meet all of the following criteria are eligible for study entry. Participants may be reassessed if not initially eligible.
• Positive asthma predictive index (API) status
• A history of at least 4 wheezing episodes in the prior year with at least one physician diagnosed or at least 3 wheezing episodes in the prior year with at least one physician diagnosed and at least 3 months of asthma controller therapy in the prior year
• Experienced a severe exacerbation requiring systemic corticosteroids, urgent unscheduled or emergency visit, or hospitalization in the 12 months before the screening visit
• All immunizations must be completed, including varicella (unless the child has already had clinical varicella). If the child needs the varicella vaccine, this will be arranged with the primary care physician and must be received before study entry.
• Allows blood to be used for genetic analysis
• Willingness to provide informed consent by the child's parent or guardian

You may not qualify if:

• Use of more than six courses of systemic corticosteroids in the 12 months before the screening visit
• More than two hospitalizations for wheezing illnesses in the 12 months before the screening visit
• Use of oral or systemic corticosteroids in the 2 weeks before the screening visit
• Current treatment with antibiotics for diagnosed sinus disease
• Current participation or has participated in the month before the screening visit in another investigational drug trial
• Evidence that the family may be unreliable or nonadherent, or may move from the clinical center area before trial completion
• Medically unable to use systemic corticosteroids
• Clinically relevant gastroesophageal reflux
• Inability of the child to cooperate with nebulizer therapy
• Participants who meet any of the following criteria are NOT eligible for enrollment, and they may not be re-enrolled:
• Gestation less than late preterm, as defined as birth before 34 weeks gestational age
• Significant developmental delay/failure to thrive, defined as crossing of two major percentile lines during the last year for age and gender. If a child plots less than the 10th percentile for age and gender, a growth chart for the previous year will be obtained from the child's primary care provider.
• Head circumference less than the 3rd percentile or greater than the 97th percentile unless medical evaluation documents no associated illness
• Presence of lung disease other than asthma, such as cystic fibrosis and bronchopulmonary dysplasia (BPD). Evaluation during the screening process will assure that an adequate evaluation of other lung diseases has been performed.
• Presence of other significant medical illnesses (e.g., cardiac, liver, gastrointestinal, endocrine) that would place the child at increased risk of participating in the study

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (5)

University of Arizona College of Medicine

Tucson, Arizona, 85724, United States

Location

Kaiser Permanente Medical Center

San Diego, California, 92111, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Zeiger RS, Mauger D, Bacharier LB, Guilbert TW, Martinez FD, Lemanske RF Jr, Strunk RC, Covar R, Szefler SJ, Boehmer S, Jackson DJ, Sorkness CA, Gern JE, Kelly HW, Friedman NJ, Mellon MH, Schatz M, Morgan WJ, Chinchilli VM, Raissy HH, Bade E, Malka-Rais J, Beigelman A, Taussig LM; CARE Network of the National Heart, Lung, and Blood Institute. Daily or intermittent budesonide in preschool children with recurrent wheezing. N Engl J Med. 2011 Nov 24;365(21):1990-2001. doi: 10.1056/NEJMoa1104647.

  PMID: 22111718 RESULT

Related Links

• Click here for the Childhood Asthma Research and Education (CARE) Network Web site

MeSH Terms

Conditions

Asthma

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

May not be applicable to young children whose asthma is more severe than that of the children in the study. Daily or intermittent use of inhaled glucocorticoids may not be efficacious in preschool-age children with transient or infrequent wheezing.

Results Point of Contact

• Title: Vernon M. Chinchilli, PhD
• Organization: Penn State Hershey College of Medicine

vchinchi@psu.edu

717-531-4262

Study Officials

• David T. Mauger, PhD

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

• Stanley J. Szefler, MD, PhD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

• Robert F. Lemanske, Jr., MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Robert S. Zeiger, MD, PhD

  Kaiser Permanente Medical Center

  PRINCIPAL INVESTIGATOR

• Robert C. Strunk, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Fernando D. Martinez, MD

  University of Arizona College of Medicine

  PRINCIPAL INVESTIGATOR

• Lynn M. Taussig, MD

  University of Denver

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair, Department of Public Health Sciences

Study Record Dates

• First Submitted: May 7, 2008
• First Posted: May 9, 2008
• Study Start: August 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: June 26, 2018
• Results First Posted: June 1, 2012

Record last verified: 2018-05

Locations

US (5)