Bronchospasm; Bronchiolitis, Bronchospasm; Bronchitis
Conditions
Keywords
Vaccine, Bronchospasm
Brief summary
The study will be conducted in two hospitals of the same geographic area. It will be included children \<3-years-old with recurrent wheezing attacks, confirmed by the review of the medical records, in the previous 12 months or a shorter time for those younger than one year.
Detailed description
This randomized, double-blind, placebo-controlled, parallel-group study will included 120 children \<3 years old with ≥3 episodes of wheezing during the previous year. They will receive active treatment or placebo for six months. The main outcome will be the number of wheezing attacks during one year. Other outcomes were duration and severity of wheezing attacks , symptom and medication scores, and use of health resources.
Interventions
BIOLOGICALBiological vaccine
daily spray (2 puff of 100 µL) for six months
Sponsors
Unidad de Investigacion Medica en Epidemiologia Clinica
Inmunotek S.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized, double-blind, placebo-controlled, multi centre, parallel-group study
Eligibility
Sex/Gender
ALL
Age
12 Months to 36 Months
Healthy volunteers
No
Inclusion criteria
* Subjects whose parents /legal representative have given written informed consent. * Both gender * Subject up to 36 months of age. * Subjects with recurrent bronchospasms (wheezing attacks); 3 or more exacerbations in the last 12 months
Exclusion criteria
* Subjects whose parents/legal representative have not given written informed consent. * Subjects out of aged range * Subjects with malignancies or chemotherapy treatment * Subjects included in another clinical trial in the last 12 months. * Subject in immunosuppressive or immunostimulatory treatment * Subjects who have received iv gamma globulin in the past 12 months. * Subjects diagnosed with candidiasis or fungal recurrent infections. * Subjects diagnosed with malabsorption syndrome * Subjects with clinical allergy to common aeroallergens in the geographical area. * Subjects with hepatitis virus infections, HIV and tuberculosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Recurrent Bronchospasm (Wheezing Attacks) | 12 months | Assessment of reduction of bronchospasm (wheezing attacks) episodes at 12 months. The number of bronchospasm (wheezing attacks) episodes, in active and placebo group will be compared |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration (Days) of Wheezing Attacks (WA) | 12 months | Review of bronchospasm (wheezing attacks) duration per patient |
| Time Until Appearance of First WA | 12 months | time (days) until appearance of first wheezing attack (WA) |
| Number of Days With Wheezing Attacks During the Study | 12 months | Review of the number of days with wheezing attacks during the study |
| Number of Patients With Recurrent WA During the Study | 12 months | Review of number of patients with recurrent WA during the whole study |
| Medication Score During WA | 12 months | Review of medication consumption during wheezing attacks. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed. Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded. The total symptom score was calculated as the sum of all individual scores during the wheezing attacks. |
| Overall Symptom Score | 12 months | Review of symptoms during the whole study. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed. Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3. The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC. The total symptom score was calculated as the sum of all individual scores during the whole study |
| Overall Medication Score | 12 months | Review of medication consumption during the whole study. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed. Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded. The total symptom score was calculated as the sum of all individual scores during the whole study. |
| Symptom Score During Wheezing Attacks | 12 months | Total of Symptom score during wheezing attacks. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed. Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3. The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC. The total symptom score was calculated as the sum of all individual scores during the wheezing attacks. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Use of Health and Social Resources During the Whole Period of the Study. | 12 months | The use of health and social resources during the study was also recorded: days of hospitalization in ward and/or intensive care unit, visits to the emergency units, unscheduled visits to the pediatrician and/or to the specialist, telephone calls to the pediatrician, complementary tests (chest radiogram, blood analysis, others), days of school absenteeism and caregiver-days when the children needed them. The data were obtained from the diary cards and confirmed through the review of medical records. Maximum value corresponds to the maximum days spent in health resources (specified above) and the minimum value corresponds to the minimum of days spent in health resources (specified above) |
Countries
Spain
Participant flow
Recruitment details
October 2012 - May 2015 subjects enrollment. 120 children \<3 years old with recurrent WA, defined as 3 or more episodes of WA during the previous year. . WA were confirmed by the review of the medical records. Aeroallergen sensitization at baseline was used as an exclusion criterion to avoid an eventual WA due to allergic asthma.
Participants by arm
| Arm | Count |
|---|---|
| Placebo The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation
Biological vaccine: daily spray (2 puff of 100 µL) for six months | 58 |
| Biological Vaccine The subjects will receive daily biological vaccines pray (2 puff of 100 µL) of for 6 months, followed by other 6 months of observation
Biological vaccine: daily spray (2 puff of 100 µL) for six months | 62 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Biological Vaccine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 62 Participants | 58 Participants | 120 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 | 23 Months STANDARD_DEVIATION 7 | 23 Months STANDARD_DEVIATION 8 | 23 Months STANDARD_DEVIATION 8 |
| Region of Enrollment Spain | 62 participants | 58 participants | 120 participants |
| Sex: Female, Male Female | 25 Participants | 26 Participants | 51 Participants |
| Sex: Female, Male Male | 37 Participants | 32 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 62 |
| other Total, other adverse events | 0 / 58 | 0 / 62 |
| serious Total, serious adverse events | 1 / 58 | 0 / 62 |
Outcome results
Primary
Number of Recurrent Bronchospasm (Wheezing Attacks)
Assessment of reduction of bronchospasm (wheezing attacks) episodes at 12 months. The number of bronchospasm (wheezing attacks) episodes, in active and placebo group will be compared
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Recurrent Bronchospasm (Wheezing Attacks) | 299 events |
| Biological Vaccine | Number of Recurrent Bronchospasm (Wheezing Attacks) | 176 events |
Secondary
Duration (Days) of Wheezing Attacks (WA)
Review of bronchospasm (wheezing attacks) duration per patient
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Duration (Days) of Wheezing Attacks (WA) | 7.9 days |
| Biological Vaccine | Duration (Days) of Wheezing Attacks (WA) | 6.0 days |
Secondary
Medication Score During WA
Review of medication consumption during wheezing attacks. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed. Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded. The total symptom score was calculated as the sum of all individual scores during the wheezing attacks.
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Medication Score During WA | 424.0 units on a scale |
| Biological Vaccine | Medication Score During WA | 164.0 units on a scale |
Secondary
Number of Days With Wheezing Attacks During the Study
Review of the number of days with wheezing attacks during the study
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Number of Days With Wheezing Attacks During the Study | 42.0 days |
| Biological Vaccine | Number of Days With Wheezing Attacks During the Study | 19.2 days |
Secondary
Number of Patients With Recurrent WA During the Study
Review of number of patients with recurrent WA during the whole study
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients With Recurrent WA During the Study | 45 Participants |
| Biological Vaccine | Number of Patients With Recurrent WA During the Study | 36 Participants |
Secondary
Overall Medication Score
Review of medication consumption during the whole study. The patients were reviewed at our clinics every three months. Medication scores were recorded daily in a diary card by the parents, who were duly instructed. Medication was rated from 0 (minimum value) and the maximum value correspond to the maximum medication consumed per 24h. Rating was according to Dreborg et al. with slight modifications: two points were given for one tablet of 4 mg of Montelukast, for one puff of 50 μg budesonide-equivalent or for one dose of oral prednisolone, and 3 for the inhalation of one puff of 200 μg budesonide-equivalent. In the case of antibiotics and antipyretic/-anti-inflammatory drugs, the number of daily doses of these drugs was recorded. The total symptom score was calculated as the sum of all individual scores during the whole study.
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Overall Medication Score | 1043.5 units on a scale |
| Biological Vaccine | Overall Medication Score | 618.5 units on a scale |
Secondary
Overall Symptom Score
Review of symptoms during the whole study. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed. Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3. The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC. The total symptom score was calculated as the sum of all individual scores during the whole study
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Overall Symptom Score | 421.0 units on a scale |
| Biological Vaccine | Overall Symptom Score | 276.5 units on a scale |
Secondary
Symptom Score During Wheezing Attacks
Total of Symptom score during wheezing attacks. The patients were reviewed at our clinics every three months. These scores were recorded daily in a diary card by the parents, who were duly instructed. Scale use to evaluate symptom during wheezing attacks is called the Symptom scores (SS) scale. Minimum value is 0 (meant improvement) and maximum value (meant not improvement) is 3. The rating was: 0=absent (no sign/symptom evident); 1=mild (sign/symptom clearly present, but easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable) and 3=severe (sign/symptom that is hard to tolerate; causes interference with activities of daily life and/or sleeping). Fever was scored as number of days with temperature over 37ºC. The total symptom score was calculated as the sum of all individual scores during the wheezing attacks.
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Symptom Score During Wheezing Attacks | 155.0 units on a scale |
| Biological Vaccine | Symptom Score During Wheezing Attacks | 80.0 units on a scale |
Secondary
Time Until Appearance of First WA
time (days) until appearance of first wheezing attack (WA)
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time Until Appearance of First WA | 5.0 days |
| Biological Vaccine | Time Until Appearance of First WA | 41.0 days |
Other Pre-specified
Use of Health and Social Resources During the Whole Period of the Study.
The use of health and social resources during the study was also recorded: days of hospitalization in ward and/or intensive care unit, visits to the emergency units, unscheduled visits to the pediatrician and/or to the specialist, telephone calls to the pediatrician, complementary tests (chest radiogram, blood analysis, others), days of school absenteeism and caregiver-days when the children needed them. The data were obtained from the diary cards and confirmed through the review of medical records. Maximum value corresponds to the maximum days spent in health resources (specified above) and the minimum value corresponds to the minimum of days spent in health resources (specified above)
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Use of Health and Social Resources During the Whole Period of the Study. | 14.5 days |
| Biological Vaccine | Use of Health and Social Resources During the Whole Period of the Study. | 11.0 days |