Trial Outcomes & Findings for CARE Network Maintenance Versus Intermittent Inhaled Steroids in Wheezing Toddlers (MIST) (NCT NCT00675584)

NCT ID: NCT00675584

Last Updated: 2018-06-26

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 278 participants
• Primary outcome timeframe: Measured during the 12-month follow-up period
• Results posted on: 2018-06-26

Participant Flow

Participant milestones

Measure	Daily Budesonide 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.	Intermittent Budesonide 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.
Overall Study STARTED	139	139
Overall Study COMPLETED	100	113
Overall Study NOT COMPLETED	39	26

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.	Total n=278 Participants Total of all reporting groups
Age, Categorical <=18 years	139 Participants n=5 Participants	139 Participants n=7 Participants	278 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	2.9 years STANDARD_DEVIATION 0.9 • n=5 Participants	2.9 years STANDARD_DEVIATION 0.9 • n=7 Participants	2.9 years STANDARD_DEVIATION 0.9 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	37 Participants n=7 Participants	86 Participants n=5 Participants
Sex: Female, Male Male	90 Participants n=5 Participants	102 Participants n=7 Participants	192 Participants n=5 Participants
Region of Enrollment United States	139 participants n=5 Participants	139 participants n=7 Participants	278 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured during the 12-month follow-up period

Population: Even if a child terminated prior to completion of the 12 months of follow-up, he/she contributed to the numerator and denominator of the exacerbation rate

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

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Rate of Exacerbations Requiring Systemic Corticosteroids	0.97 events per years of follow-up Interval 0.76 to 1.22	0.95 events per years of follow-up Interval 0.75 to 1.2

SECONDARY outcome

Timeframe: Measured during the 12-month follow-up period

Population: Even if a child terminated prior to completion of the 12 months of follow-up, he/she contributed to the numerator and denominator of the proportion of episode-free days

An episode-free day consisted of no asthma symptoms and no asthma rescue medications

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Proportion of Episode-free Days	0.78 proportion of episode-free days Interval 0.76 to 0.81	0.78 proportion of episode-free days Interval 0.75 to 0.8

SECONDARY outcome

Timeframe: Measured during the 12-month follow-up period

Population: Even if a child terminated prior to completion of the 12 months of follow-up, he/she contributed to the number of urgent care visits

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Number of Urgent Care Visits, Emergency Department Visits, or Hospitalizations for Wheezing or Asthma Per 12 Months	2.40 visits per 12 months Interval 1.91 to 3.02	2.37 visits per 12 months Interval 1.89 to 2.97

SECONDARY outcome

Timeframe: Measured during the 12-month follow-up period

Population: Even if a child terminated prior to completion of the 12 months of follow-up, his/her data were included in the assessment of treatment failure

Treatment failure was defined as the occurrence of at least one of the following events:

1. four courses of systemic corticosteroids

2. one hospitalization for acute exacerbation of wheezing

3. hypoxic seizure during an acute exacerbation of asthma/wheezing

4. intubation for acute asthma/wheezing

5. serious adverse event related to a study medication

6. physician discretion with specific rationale

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Number of Participants With Treatment Failure	17 Participants	9 Participants

SECONDARY outcome

Timeframe: baseline and 12 months

Population: Even if a child terminated prior to completion of the 12 months of follow-up, his/her data were included in the analysis based on the linear mixed-effects model

Exhaled nitric oxide (eNO) is measured in parts per billion, and the change constructed between 12 months and baseline

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Change Between 12 Months and Baseline in Exhaled Nitric Oxide (eNO)	-0.14 parts per billion Interval -0.32 to 0.04	-0.18 parts per billion Interval -0.38 to 0.02

SECONDARY outcome

Timeframe: baseline and 12 months

Population: Prior to enrollment of the first randomized study participant, the clinical investigators decided that it would be futile to perform oscillometry in children of the target age range for MIST (2-5 years of age). A previous CARE Network trial (PEAK) performed oscillometry in such children, but the data were highly variable and of poor quality.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Measured during the 12-month follow-up period

Population: All randomized children are included

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Adverse Events Associated With Corticosteroid Use	3 Participants	0 Participants

SECONDARY outcome

Timeframe: Measured during the 12-month follow-up period

Population: Even if a child terminated prior to completion of the 12 months of follow-up, he/she contributed to the number of days

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Number of Days of Absence From Daycare and Preschool for the Child and From Work for the Caregiver Per 12 Months	3.02 days per 12 months Interval 2.22 to 4.12	2.72 days per 12 months Interval 2.0 to 3.7

SECONDARY outcome

Timeframe: Measured during the 12-month follow-up period

Population: Even if a child terminated prior to completion of the 12 months of follow-up, he/she contributed to the number of days

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Proportion of Days With Rescue Albuterol Use	0.05 proportion of days Interval 0.04 to 0.06	0.06 proportion of days Interval 0.05 to 0.07

SECONDARY outcome

Timeframe: Measured during the first seven days for each respiratory tract illness

Population: The data from every respiratory tract illness is included in the analysis

Wheeze severity is scored as 0 (none) to 5 (very severe) during a respiratory tract illness

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Change in Wheeze Severity During a Respiratory Tract Illness	0.5 units on a scale Interval 0.1 to 0.8	0.8 units on a scale Interval 0.5 to 1.1

SECONDARY outcome

Timeframe: baseline and 12 months

Population: Even if a child terminated prior to completion of the 12 months of follow-up, his/her data were included in the analysis based on the linear mixed-effects model

The caregiver quality-of-life questionnaire consists of seven questions, each scored from 0 (worse) to 3 (best), and all seven questions are summed to yield a total score ranging from 0 to 21

Outcome measures

Measure	Daily Budesonide n=139 Participants 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.	Intermittent Budesonide n=139 Participants 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.
Change Between 12 Months and Baseline in the Caregiver Quality-of-life	1.4 units on a scale Interval -3.0 to 5.8	2.0 units on a scale Interval -1.8 to 5.8

Adverse Events

Daily Budesonide

Serious events: 7 serious events

Other events: 9 other events

Deaths: 0 deaths

Intermittent Budesonide

Serious events: 10 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Daily Budesonide n=139 participants at risk 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.	Intermittent Budesonide n=139 participants at risk 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.
Respiratory, thoracic and mediastinal disorders hospitalization due to exacerbation	2.9% 4/139 • Number of events 4 • 1 year does not differ from the clinicaltrials.gov definitions	3.6% 5/139 • Number of events 5 • 1 year does not differ from the clinicaltrials.gov definitions
Injury, poisoning and procedural complications other	2.2% 3/139 • Number of events 3 • 1 year does not differ from the clinicaltrials.gov definitions	3.6% 5/139 • Number of events 5 • 1 year does not differ from the clinicaltrials.gov definitions

Other adverse events

Measure	Daily Budesonide n=139 participants at risk 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.	Intermittent Budesonide n=139 participants at risk 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.
Gastrointestinal disorders nausea or vomiting	6.5% 9/139 • Number of events 9 • 1 year does not differ from the clinicaltrials.gov definitions	7.9% 11/139 • Number of events 11 • 1 year does not differ from the clinicaltrials.gov definitions

Additional Information

Vernon M. Chinchilli, PhD

Penn State Hershey College of Medicine

Phone: 717-531-4262

Email: vchinchi@psu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place