Efficacy and Safety Evaluation in Recurrent Wheezing Attacks

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Double-blind Placebo-controlled, Parallel, Multi Centre Clinical Trial of Sublingual Bacterial Vaccine in Children With Recurrent Bronchospasm (Wheezing Attacks) for the Evaluation of Efficacy, Security and Clinical Impact.

Conditions
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Bronchospasm; Bronchiolitis, Bronchospasm; Bronchitis

Intervention / Treatment
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* Biological: Biological vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 36 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, multi centre, parallel-group study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>The subjects will receive daily placebo spray (2 puff of 100 µL) for 6 months, followed by other 6 months of observation | Biological: Biological vaccine<br>* daily spray (2 puff of 100 µL) for six months<br>|
| Experimental: Biological vaccine<br>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: Biological vaccine<br>* daily spray (2 puff of 100 µL) for six months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration (Days) of Wheezing Attacks (WA) | Review of bronchospasm (wheezing attacks) duration per patient | 12 months | 
| Time Until Appearance of First WA | time (days) until appearance of first wheezing attack (WA) | 12 months | 
| Number of Days With Wheezing Attacks During the Study | Review of the number of days with wheezing attacks during the study | 12 months | 
| Number of Patients With Recurrent WA During the Study | Review of number of patients with recurrent WA during the whole study | 12 months | 
| 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. | 12 months | 
| 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. | 12 months | 
| 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 | 12 months | 
| 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. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Bronchospasm