Asthma
Conditions
Keywords
wheezing, asthma, childhood, OM-85 BV, Broncho-Vaxom
Brief summary
The purpose of this study is to determine whether OM-85 BV (Broncho-Vaxom)has any effect on respiratory infections, infection related wheezing attacks, beta-2 agonist use, duration of attacks and effect on serum cytokine levels.
Detailed description
Context: Respiratory infections are the major cause of wheezing attacks in children with recurrent wheezing or asthma in preschool age. OM-85 BV is an bacteria lysate which has been proven to prevent respiratory infections about 40 percent in children. Objective: To determine if using OM-85 BV diminish the number and duration of the respiratory infections and respiratory infection related wheezing attacks,beta-2 agonist and steroid use, and number and duration of hospitalizations in children with recurrent wheezing and asthma. And also to determine if OM-85 BV has any effect on serum cytokine levels after 6 months. Study Design/Setting/Participants: A double-blind, randomized, controlled trial of OM-85 BV versus placebo for children 6 months to 6 years of age who have respiratory tract infection related recurrent wheezing attacks. Intervention: Participants will receive either active Broncho-Vaxom or placebo for 3 months. Study Measures: They follow up for 1 year for number and duration of wheezing attacks, number, type and duration of respiratory infections, number and duration of beta-2 agonist use, number and duration of steroid use and number and duration of hospitalizations. Serum cytokine levels will measure to determine if Broncho-Vaxom has any effect on serum cytokine levels (at the beginning of the trial and sixth months of the trial).
Interventions
DRUGOM-85 BV (Broncho-Vaxom)
3.5 mg capsule, 1 capsule per day for first 10 day of the month, for 3 months
DRUGOM-85 BV (placebo)
3.5 mg oral placebo capsule, 1 placebo capsule per day for first 10 days of the months for 3 months
Sponsors
Kecioren Education and Training Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 6 Years
Healthy volunteers
No
Inclusion criteria
* Children with recurrent wheezing who had at least 3 wheezing attacks in the last 6 months * Children with asthma who had at least 3 wheezing attacks in the last 6 months
Exclusion criteria
* Chronic lung disease * Immun deficiency * Malabsorption * Anatomic abnormalities of the respiratory tract * Gastroesophageal reflux disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Rate of Wheezing Attacks | 12 months | Acute wheezing attack was defined as episode of progressive increase in shortness of breath, cough, wheezing, retraction of the chest and chest tightness, or combination of these symptoms. When wheezing attack occured it was Over the 12 months of the study mean number (rate) of wheezing attacks/per patient was calculated and compared with placebo. This outcome measure was calculated by dividing cumulative wheezing attacks to number of participants in each group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Common Cold | 12 months | All the common colds were recorded during the 12 months of the study. At the and of the study period the two groups were compared according to the number of common-cold/per patient over the 12 months of the trial. This outcome was calculated by dividing cumulative number of common colds by number of participants in each group over the 12 months of the trial. |
| Number of Wheezing Attacks That Required Systemic Steroid Therapy | 12 months | All the wheezing attacks which were enough severe to require systemic steroid therapy were recorded over the 12 months of the study. At the and of the study period, number of wheezing attacks that required systemic steroid therapy/per patients were calculated. This outcome was calculated by dividing cumulative number of wheezing attacks that required systemic steroid therapy by number of participants in each group. |
| Mean Duration (in Day) of Wheezing Attacks Per Patient | 12 months | Over the 12 months of the study we calculated mean duration of each wheezing attacks/per patients.This measure was calculated separately for each participants by dividing duration of wheezing attacks to number of wheezing attacks. |
| Duration of Hospitalization/Per Patient | 12 months | Over the 12 months of the study we calculated mean duration of hospitalization/per patients. |
| Effect of OM-85 BV on Cytokine Levels | 6 months | Cytokine levels were not measured during the trial because of unavailability of laboratory resources. |
| Number of Hospitalizations | 12 months | During the study period of 12 months all hospitalizations for wheezing attacks were recorded. Over the 12 months of the trial mean number of hospitalizations/per patients were calculated. This outcome was calculated by dividing cumulative number of hospitalizations by number of participants in each group over the 12 months of the trial. |
Countries
Turkey (Türkiye)
Participant flow
Recruitment details
This study was a randomized, double-blind, placebo-controlled, parallel group study with OM-85 (Broncho-Vaxom; OM PHARMA; Meyrin/Geneva, Switzerland) in patients with recurrent wheezing and performed between August 2007- September 2008 in the outpatient department of Pediatric Allergy of Kecioren Education and Research Hospital in Ankara, Turkey.
Pre-assignment details
This study comprise 3 months of active treatment and 9 months of follow-up. Duration of the trial was 12 months. Eighty of 100 children were selected to enter the trial. 20 children were not included in to the study because of not meeting the inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Broncho-Vaxom Group This group consists of 35 children with recurrent wheezing who received one capsule per oral, OM-85 BV (3.5 mg) per day for the first 10 consecutive days of each month for 3 consecutive months. | 40 |
| Placebo Group This group consists of 40 children with recurrent wheezing who received one capsule per oral, placebo per day for the first 10 consecutive days of each month for 3 consecutive months. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | moved to another place | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Group | Broncho-Vaxom Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 40 Participants | 40 Participants | 80 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 2.65 years STANDARD_DEVIATION 1.69 | 2.51 years STANDARD_DEVIATION 1.48 | 2.59 years STANDARD_DEVIATION 0.59 |
| Region of Enrollment Turkey | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 13 Participants | 12 Participants | 25 Participants |
| Sex: Female, Male Male | 27 Participants | 28 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 35 | 2 / 40 |
| serious Total, serious adverse events | 0 / 35 | 0 / 40 |
Outcome results
Primary
Mean Rate of Wheezing Attacks
Acute wheezing attack was defined as episode of progressive increase in shortness of breath, cough, wheezing, retraction of the chest and chest tightness, or combination of these symptoms. When wheezing attack occured it was Over the 12 months of the study mean number (rate) of wheezing attacks/per patient was calculated and compared with placebo. This outcome measure was calculated by dividing cumulative wheezing attacks to number of participants in each group.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Broncho-Vaxom Group | Mean Rate of Wheezing Attacks | 3.57 wheezing attacks/per patient | Standard Error 1.61 |
| Placebo Group | Mean Rate of Wheezing Attacks | 5.72 wheezing attacks/per patient | Standard Error 2.72 |
Comparison: The sample size was computed to prove that a 30% decrease of the rate of virus provoked wheezing attacks in the OM-85 group compared with placebo is statistically significant. Approximately 29 analyzable participants in each group were required, with α=0.05 and β=0.10 (ie, with a power of 90%), respectively. The difference of 30% was taken from both pilot study and clinical experience. Sample size estimation was performed by using NCSS and PASS 2000 software.p-value: 0.0595% CI: [-3.2, -1.1]Wilcoxon (Mann-Whitney)
Secondary
Duration of Hospitalization/Per Patient
Over the 12 months of the study we calculated mean duration of hospitalization/per patients.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Broncho-Vaxom Group | Duration of Hospitalization/Per Patient | 0.82 day/per patient | Standard Error 0.35 |
| Placebo Group | Duration of Hospitalization/Per Patient | 2.02 day/per patient | Standard Error 0.71 |
p-value: 0.45295% CI: [-2.87, 0.42]Wilcoxon (Mann-Whitney)
Secondary
Effect of OM-85 BV on Cytokine Levels
Cytokine levels were not measured during the trial because of unavailability of laboratory resources.
Time frame: 6 months
Secondary
Mean Duration (in Day) of Wheezing Attacks Per Patient
Over the 12 months of the study we calculated mean duration of each wheezing attacks/per patients.This measure was calculated separately for each participants by dividing duration of wheezing attacks to number of wheezing attacks.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Broncho-Vaxom Group | Mean Duration (in Day) of Wheezing Attacks Per Patient | 5.57 day/per patient | Standard Error 0.35 |
| Placebo Group | Mean Duration (in Day) of Wheezing Attacks Per Patient | 7.66 day/per patient | Standard Error 0.33 |
p-value: <0.00195% CI: [-3.06, -1.01]Wilcoxon (Mann-Whitney)
Secondary
Number of Common Cold
All the common colds were recorded during the 12 months of the study. At the and of the study period the two groups were compared according to the number of common-cold/per patient over the 12 months of the trial. This outcome was calculated by dividing cumulative number of common colds by number of participants in each group over the 12 months of the trial.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Broncho-Vaxom Group | Number of Common Cold | 3.51 common cold/per patients | Standard Error 0.26 |
| Placebo Group | Number of Common Cold | 5.62 common cold/per patients | Standard Error 0.31 |
p-value: <0.00195% CI: [-2.94, -1.27]Wilcoxon (Mann-Whitney)
Secondary
Number of Hospitalizations
During the study period of 12 months all hospitalizations for wheezing attacks were recorded. Over the 12 months of the trial mean number of hospitalizations/per patients were calculated. This outcome was calculated by dividing cumulative number of hospitalizations by number of participants in each group over the 12 months of the trial.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Broncho-Vaxom Group | Number of Hospitalizations | 0.14 hospitalization/per patient | Standard Error 0.05 |
| Placebo Group | Number of Hospitalizations | 0.40 hospitalization/per patient | Standard Error 0.12 |
p-value: 0.19595% CI: [-0.55, 0.03]Wilcoxon (Mann-Whitney)
Secondary
Number of Wheezing Attacks That Required Systemic Steroid Therapy
All the wheezing attacks which were enough severe to require systemic steroid therapy were recorded over the 12 months of the study. At the and of the study period, number of wheezing attacks that required systemic steroid therapy/per patients were calculated. This outcome was calculated by dividing cumulative number of wheezing attacks that required systemic steroid therapy by number of participants in each group.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Broncho-Vaxom Group | Number of Wheezing Attacks That Required Systemic Steroid Therapy | 0.57 wheezing attacks/per patient | Standard Error 0.14 |
| Placebo Group | Number of Wheezing Attacks That Required Systemic Steroid Therapy | 0.90 wheezing attacks/per patient | Standard Error 0.16 |
p-value: 0.1195% CI: [-0.77, 0.11]Wilcoxon (Mann-Whitney)