Asthma
Conditions
Brief summary
A new influenza vaccine, known as LAIV (Live Attenuated Intranasal Vaccine) has recently been approved by a number of licensing boards and is given by a spray into the nose. In the United Kingdom (UK), the vaccine has been demonstrated to be highly effective against influenza infection. Further, despite concerns that LAIV can cause wheezing in children under age 2 years, the previous SNIFFLE studies have demonstrated it to be safe in children over 2 years with mild-moderate asthma. The objective of this multicentre study is to further assess the safety of intranasal LAIV in children with asthma and recurrent wheeze, including those with severe symptoms.
Interventions
Sponsors
Public Health England
Imperial College London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Aged 2 - 18 years old (inclusive) * Physician diagnosis of asthma or recurrent wheezing (by the hospital specialist) AND (i) in children age 2-4 years: ≥2 exacerbations in the past year requiring oral steroids or observation in-hospital beyond 4 hours duration, OR (ii) in children ≥ 5 years of age, receiving treatment equivalent to at least BTS/SIGN step 2 therapy. * Written informed consent from parent/guardian (or the patient themselves from age 16 years), with assent from children aged 8 years and above wherever possible.
Exclusion criteria
1. Admission to Paediatric Intensive Care for invasive ventilation due to a respiratory illness in the preceding 2 years. 2. Contraindications to LAIV (notwithstanding allergy to egg protein), which include: 1. Hypersensitivity to the active ingredients, gelatin or gentamicin (a possible trace residue) 2. Previous systemic allergic reaction to LAIV 3. Previous allergic reaction to an influenza vaccine (not LAIV) is a relative contra-indication, which must be discussed with the site PI to confirm patient suitability 4. Children/adolescents who are clinically immunodeficient due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids\*\*. \*\*High-dose steroids is defined as a treatment course for at least one month, equivalent to a dose greater than 20mg prednisolone per day (any age), or for children under 20kg, a dose greater than 1mg/kg/day. NB: LAIV is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled/low-dose oral systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency. 5. Children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection. 6. pregnancy 3. Contraindications to vaccination on that occasion, e.g. due to child being acutely unwell: 1. Febrile ≥38.0 degrees C in last 72 hours 2. \*Acute wheeze in last 72 hours requiring treatment beyond that normally prescribed for regular use by the child's treating healthcare professional 3. \*Recent admission to hospital in last 2 weeks for acute asthma 4. \*Current oral steroid for asthma exacerbation or course completed within last 2 weeks 5. Any other significant condition or circumstance which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study. * Items 3b-3d are relative contra-indications: Many children with difficult-to-control symptoms may meet fail to meet these criteria on a routine basis. Where these are present, the study centre PIs are able to authorise participation on a case-by-case basis, after assessing the child and their lung function at the time of enrolment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Asthma Symptoms and Control Pre and 4 Weeks Post LAIV, as Assessed by Validated Questionnaire | 4 weeks post LAIV | The validated questionnaire to be used will depend on the age of the enrolled child: * Age 2-4 years: TRACK questionnaire * Age 5-11 years: Children's Asthma Control Test (C-ACT) score * Age 12+ years: Asthma Control Test (ACT) score The change in score (using the appropriate questionnaire for age) between pre- and 4 weeks post LAIV will be used to assess the primary outcome across all participants. a change in (c-)ACT of at least 3 points, or 10 points for TRACK will be determined a significant change. For TRACK, the minimum and maximum score possible is 0 and 100 respectively, the higher the score, the better is symptom control. For c-ACT, the minimum and maximum score possible is 0 and 27 respectively, the higher the score, the better controlled are asthma symptoms. For ACT, the minimum and maximum score possible is 5 and 25 respectively, the higher the score, the better controlled are asthma symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AE) and Serious Adverse Events (SAEs) in Children Receiving LAIV | Up to 4 weeks post LAIV administration | Incidence of a 'significant exacerbation' in asthma, defined as: i. At least 3 day course of oral steroids following an unscheduled contact with a healthcare professional; OR ii. Unscheduled visit to an Emergency department or admission to hospital for treatment of asthma symptoms, requiring systemic corticosteroids |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Asthma LAIV administration in children with asthma receiving treatment according to British Thoracic Society step 2+
Administration of Live attenuated influenza vaccine (LAIV) | 478 |
| Total | 478 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Invalid consent | 1 |
Baseline characteristics
| Characteristic | Asthma | — |
|---|---|---|
| Age, Categorical <=18 years | 476 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 2 Participants | — |
| Age, Continuous | 9.3 years | — |
| British Thoracic Society (BTS) Treatment Step 4+ | 229 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United Kingdom | 478 participants | — |
| Sex: Female, Male Female | 190 Participants | — |
| Sex: Female, Male Male | 288 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 478 |
| other Total, other adverse events | 150 / 478 |
| serious Total, serious adverse events | 4 / 478 |
Outcome results
Primary
Change in Asthma Symptoms and Control Pre and 4 Weeks Post LAIV, as Assessed by Validated Questionnaire
The validated questionnaire to be used will depend on the age of the enrolled child: * Age 2-4 years: TRACK questionnaire * Age 5-11 years: Children's Asthma Control Test (C-ACT) score * Age 12+ years: Asthma Control Test (ACT) score The change in score (using the appropriate questionnaire for age) between pre- and 4 weeks post LAIV will be used to assess the primary outcome across all participants. a change in (c-)ACT of at least 3 points, or 10 points for TRACK will be determined a significant change. For TRACK, the minimum and maximum score possible is 0 and 100 respectively, the higher the score, the better is symptom control. For c-ACT, the minimum and maximum score possible is 0 and 27 respectively, the higher the score, the better controlled are asthma symptoms. For ACT, the minimum and maximum score possible is 5 and 25 respectively, the higher the score, the better controlled are asthma symptoms.
Time frame: 4 weeks post LAIV
Population: 4 week follow-up data available in 319/478 participants
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Asthma | Change in Asthma Symptoms and Control Pre and 4 Weeks Post LAIV, as Assessed by Validated Questionnaire | Improvement >= MID | 28 Participants |
| Asthma | Change in Asthma Symptoms and Control Pre and 4 Weeks Post LAIV, as Assessed by Validated Questionnaire | No change | 254 Participants |
| Asthma | Change in Asthma Symptoms and Control Pre and 4 Weeks Post LAIV, as Assessed by Validated Questionnaire | Deterioration >= MID | 37 Participants |
p-value: 0.26McNemar
Secondary
Incidence of Adverse Events (AE) and Serious Adverse Events (SAEs) in Children Receiving LAIV
Incidence of a 'significant exacerbation' in asthma, defined as: i. At least 3 day course of oral steroids following an unscheduled contact with a healthcare professional; OR ii. Unscheduled visit to an Emergency department or admission to hospital for treatment of asthma symptoms, requiring systemic corticosteroids
Time frame: Up to 4 weeks post LAIV administration
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Asthma | Incidence of Adverse Events (AE) and Serious Adverse Events (SAEs) in Children Receiving LAIV | 47 Participants |