Childhood Asthma Research and Education (CARE) Network Trial - Maintenance Versus Intermittent Inhaled Steroids in Wheezing Toddlers (MIST)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Vernon M. Chinchilli, PhD, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT00675584
First received: May 7, 2008
Last updated: February 24, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Budesonide
Drug: Placebo Budesonide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Childhood Asthma Research and Education (CARE) Network Trial - Maintenance Versus Intermittent Inhaled Steroids in Wheezing Toddlers (MIST)

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • Rate of Exacerbations Requiring Systemic Corticosteroids [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
    The rate of exacerbations was calculated as the number of exacerbations requiring prednisone per years of follow-up


Secondary Outcome Measures:
  • Proportion of Episode-free Days [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  • Rate of Urgent Care Visits, Emergency Department Visits, or Hospitalizations for Wheezing or Asthma [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  • Time to Treatment Failure [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  • Changes in Exhaled Nitric Oxide Levels [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  • Changes in Pulmonary Reactance and Resistance [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  • Adverse Events Associated With Corticosteroid Use [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: Yes ]
  • Absences From Daycare and Preschool for the Child and From Work for the Caregiver [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  • Rate of Rescue Albuterol Use [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  • Symptom Severity During Respiratory Tract Illness [ Time Frame: Measured at 7 days for each respiratory tract illness ] [ Designated as safety issue: No ]
  • Caregiver Quality of Life [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]

Enrollment: 278
Study Start Date: August 2008
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
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
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.
Other Name: Pulmicort Respules®
Drug: Placebo Budesonide
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.
Experimental: 2
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
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.
Other Name: Pulmicort Respules®
Drug: Placebo Budesonide
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.

Detailed Description:

Childhood asthma can be caused by many factors, including allergens, cigarette smoke, air pollution, or infections. Symptoms include wheezing, shortness of breath, chest tightness, and coughing. Wheezing illnesses are common during the first several years of life, and continuous wheezing, or recurrent intermittent wheezing, may be an indicator of asthma. Recurrent intermittent wheezing can also lead to breathing difficulties, sleep disturbances, and severe exacerbations that result in emergency department visits, hospitalizations, or even death. The Prevention of Early Asthma in Kids (PEAK) and Acute Intervention Management Strategies (AIMS) studies, both of which are part of the Childhood Asthma Research and Education (CARE) Network, as well as several other studies, have identified therapies that may improve recurrent wheezing in young children. This study will compare the safety and effectiveness of two treatment regimens—low doses of ICS taken on a daily basis versus higher doses of ICS taken only during respiratory tract illnesses—at improving recurrent wheezing in toddlers. Study researchers will also identify individual characteristics (e.g., age, gender, family history of asthma and allergies, the degree of allergy, genetics) that may be associated with treatment response. Lastly, the relationship of virus infections to respiratory illnesses, wheezing episodes, and response to study treatments will also be studied.

This study will enroll children between 12 and 53 months of age who have experienced episodes of wheezing or coughing in the year before study entry, with at least one episode that required one of the following: oral steroids, an urgent unscheduled medical visit, an emergency room visit, or hospitalization. This study will begin with a 2-week evaluation period during which potential participants will receive placebo once a day. Parents will document their child's asthma symptoms and medication use in a daily diary. Next, at a baseline study visit, eligible participants will be randomly assigned to one of the following two 12-month treatment groups:

  • Group 1 participants will receive a low dose of ICS once a day at night, except during respiratory tract illnesses. During a respiratory tract illness, participants will receive placebo each morning and a low dose of ICS each night for 7 days.
  • Group 2 participants will receive a high dose of ICS twice a day for 7 days during each respiratory illness and placebo once a day at night at all other times.

Throughout the 12 months of treatment, all participants will receive albuterol to treat respiratory symptoms and prednisolone if asthma symptoms worsen. Parents will be given an action plan to help manage their child's symptoms, and during respiratory illnesses, parents will contact study researchers to determine the best treatment plan. Study visits will occur at baseline and Weeks 4, 12, 20, 28, 36, 44, and 52. Participants' parents will take part in scheduled telephone interviews one month after each clinic visit to provide information on their child's asthma symptoms, study medication use, and health problems. Most study visits will include a physical exam and lung function testing. At select study visits, the following will occur: allergy skin testing, blood collection, nasal mucus sampling, and parent questionnaires to assess asthma, quality of life, and environmental factors. A portion of the participants' blood will undergo genetic analysis; a blood collection from parents for genetic analysis will be optional. Throughout the treatment period, participants' parents will record asthma symptoms and medication usage in a daily diary.

  Eligibility

Ages Eligible for Study:   12 Months to 53 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria at Screening Visit:

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

Exclusion Criteria at Screening Visit:

Participants who meet any of the following criteria are NOT eligible for enrollment, but they may be re-enrolled if these exclusion criteria disappear:

  • 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
  • Immunodeficiency disorders
  • History of respiratory failure requiring mechanical ventilation
  • History of hypoxic seizure
  • History of significant adverse reaction to any study medication ingredient

Exclusion Criteria at Baseline Visit:

Participants will be ineligible to continue in the study and be randomly assigned to a treatment group if any of the following is documented during the 2-week observation period, but they may be re-enrolled if these exclusion criteria disappear:

  • Persistent symptomatic asthma, as defined as experiencing symptoms requiring albuterol use on average three or more days per week or two or more night time awakenings due to asthma-associated symptoms
  • Inadequate adherence (less than 75% of days) to diary card completion or nebulizer medication use
  • Use of any asthma medication except albuterol (used on as needed basis)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00675584

Locations
United States, Arizona
University of Arizona College of Medicine
Tucson, Arizona, United States, 85724
United States, California
Kaiser Permanente Medical Center
San Diego, California, United States, 92111
United States, Colorado
National Jewish Medical and Research Center
Denver, Colorado, United States, 80206
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin - Madison
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: 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
Study Chair: Lynn M. Taussig, MD University of Denver
  More Information

Additional Information:
Publications:
Responsible Party: Vernon M. Chinchilli, PhD, Professor and Chair, Department of Public Health Sciences, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00675584     History of Changes
Other Study ID Numbers: 581, 5U10HL064313, 5U10HL064288, 5U10HL064305, 5U10HL064295, 5U10HL064287, 5U10HL064307
Study First Received: May 7, 2008
Results First Received: April 30, 2012
Last Updated: February 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Budesonide
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on August 21, 2014