Clinical trial NCT02866942: Safety of Nasal Influenza Immunisation in Children With Asthma
Official title: Safety of Nasal Influenza Immunisation in Children With Asthma - The SNIFFLE-4 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Public Health England
First posted: 2016-08-15
Enrollment: 479
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Asthma Symptoms and Control Pre and 4 Weeks Post LAIV, as Assessed by Validated Questionnaire
timeFrame: 4 weeks post LAIV
Secondary outcomes:
measure: Incidence of Adverse Events (AE) and Serious Adverse Events (SAEs) in Children Receiving LAIV
timeFrame: Up to 4 weeks post LAIV administration
Other outcomes:
Locations:
Study officials:
affiliation: Imperial College London / Imperial College Healthcare NHS Trust / Public Health England
name: Paul J Turner
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Turner 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.
citation: Jackson 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.