AsthmaPhase 4SNIFFLE-4NCT02866942
Safety of Nasal Influenza Immunisation in Children With Asthma
A Phase 4 study testing Administration of Live attenuated influenza vaccine (LAIV) in people with Asthma, run by Imperial College London.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Asthma
- What is being tested?
- Administration of Live attenuated influenza vaccine (LAIV)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 479 participants
- Where
- No sites listed yet
- Study dates
- Oct 2016to Mar 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- Admission to Paediatric Intensive Care for invasive ventilation due to a respiratory illness in the preceding 2 years.
- Contraindications to LAIV (notwithstanding allergy to egg protein), which include:
- Hypersensitivity to the active ingredients, gelatin or gentamicin (a possible trace residue)
- Previous systemic allergic reaction to LAIV
- 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
- 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**.
Show all 17Show fewer
- 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.
- 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.
- pregnancy
- Contraindications to vaccination on that occasion, e.g. due to child being acutely unwell:
- Febrile ≥38.0 degrees C in last 72 hours
- *Acute wheeze in last 72 hours requiring treatment beyond that normally prescribed for regular use by the child's treating healthcare professional
- *Recent admission to hospital in last 2 weeks for acute asthma
- *Current oral steroid for asthma exacerbation or course completed within last 2 weeks
- 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.
About this study
Official title: Safety of Nasal Influenza Immunisation in Children With Asthma - The SNIFFLE-4 Study
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.
- Conditions
- Asthma
- Being tested
- Administration of Live attenuated influenza vaccine (LAIV)
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration of Live attenuated influenza vaccine (LAIV)Drug
Also called Flumist, Fluenz
| Study group | Role | What they receive |
|---|---|---|
| Asthma | Experimental | LAIV administration in children with asthma receiving treatment according to British Thoracic Society step 2+ Receives: Drug: Administration of Live attenuated influenza vaccine (LAIV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks post LAIV
Secondary outcomes (1)
Incidence of Adverse Events (AE) and Serious Adverse Events (SAEs) in Children Receiving LAIV
Incidence of a 'significant exacerbation' in asthma, defined as:
- 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
Measured: Up to 4 weeks post LAIV administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2016 (estimated)
- Study startOct 2016
- Primary completionMar 2017
- Study completionMar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 479 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Public Health England
- Responsible party
- Principal investigator, Paul Turner, Imperial College London
- Investigators
- Paul J Turner, Principal investigator, Imperial College London / Imperial College Healthcare NHS Trust / Public Health England
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02866942
- Sponsor's protocol ID
- 16SM3348
- Other IDs
- 2016-002352-24, 2016
- Acronym
- SNIFFLE-4
- Status last verified
- May 2019
- First submitted
- 4 Aug 2016
- Last updated
- 10 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Turner PJ, Southern J, Andrews NJ, Miller E, Erlewyn-Lajeunesse M; SNIFFLE Study Investigators. Safety of live attenuated influenza vaccine in atopic children with egg allergy. J Allergy Clin Immunol. 2015 Aug;136(2):376-81. doi: 10.1016/j.jaci.2014.12.1925. Epub 2015 Feb 13.
PubMed 25684279Turner PJ, Southern J, Andrews NJ, Miller E, Erlewyn-Lajeunesse M; SNIFFLE-2 Study Investigators. Safety of live attenuated influenza vaccine in young people with egg allergy: multicentre prospective cohort study. BMJ. 2015 Dec 8;351:h6291. doi: 10.1136/bmj.h6291.
PubMed 26645895Jackson D, Pitcher M, Hudson C, Andrews N, Southern J, Ellis J, Hoschler K, Pebody R, Turner PJ, Miller E, Zambon M. Viral Shedding in Recipients of Live Attenuated Influenza Vaccine in the 2016-2017 and 2017-2018 Influenza Seasons in the United Kingdom. Clin Infect Dis. 2020 Jun 10;70(12):2505-2513. doi: 10.1093/cid/ciz719.
PubMed 31642899
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Nasal Influenza Immunisation in Children With Asthma - The SNIFFLE-4 Study
- ClinicalTrials.gov ID
- NCT02866942
- Acronym / sponsor ID
- SNIFFLE-4 / 16SM3348
- Conditions
- Asthma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 479 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Public Health England
- Study start
- Oct 2016 (actual)
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 15 Aug 2016 (estimated)
- Results
- Posted 26 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Asthma | Experimental | Drug: Administration of Live attenuated influenza vaccine (LAIV)LAIV administration in children with asthma receiving treatment according to British Thoracic Society step 2+ |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (17 listed)
- Admission to Paediatric Intensive Care for invasive ventilation due to a respiratory illness in the preceding 2 years.
- Contraindications to LAIV (notwithstanding allergy to egg protein), which include:
- 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.
- Contraindications to vaccination on that occasion, e.g. due to child being acutely unwell:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Administration of Live attenuated influenza vaccine (LAIV)Also: Flumist, Fluenz | Drug | Asthma |
Primary outcome
Change in Asthma Symptoms and Control Pre and 4 Weeks Post LAIV, as Assessed by Validated Questionnaire
Time frame: 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.
1 secondary outcome
Incidence of Adverse Events (AE) and Serious Adverse Events (SAEs) in Children Receiving LAIV
Time frame: Up to 4 weeks post LAIV administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25684279Turner PJ, Southern J, Andrews NJ, Miller E, Erlewyn-Lajeunesse M; SNIFFLE Study Investigators. Safety of live attenuated influenza vaccine in atopic children with egg allergy. J Allergy Clin Immunol. 2015 Aug;136(2):376-81. doi: 10.1016/j.jaci.2014.12.1925. Epub 2015 Feb 13.
- Background: PubMed 26645895Turner PJ, Southern J, Andrews NJ, Miller E, Erlewyn-Lajeunesse M; SNIFFLE-2 Study Investigators. Safety of live attenuated influenza vaccine in young people with egg allergy: multicentre prospective cohort study. BMJ. 2015 Dec 8;351:h6291. doi: 10.1136/bmj.h6291.
- Derived from this study: PubMed 31642899Jackson D, Pitcher M, Hudson C, Andrews N, Southern J, Ellis J, Hoschler K, Pebody R, Turner PJ, Miller E, Zambon M. Viral Shedding in Recipients of Live Attenuated Influenza Vaccine in the 2016-2017 and 2017-2018 Influenza Seasons in the United Kingdom. Clin Infect Dis. 2020 Jun 10;70(12):2505-2513. doi: 10.1093/cid/ciz719.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul J Turner principal investigator
Imperial College London / Imperial College Healthcare NHS Trust / Public Health England
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Administration of Live attenuated influenza vaccine (LAIV) in people with Asthma, run by Imperial College London.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 May 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Asthma Symptoms and Control Pre and 4 Weeks Post LAIV, as Assessed by Validated Questionnaire (time frame: 4 weeks post LAIV). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02866942, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2019.