The effect of live attenuated inactivated influenza vaccine on experimental human pneumococcal carriage study
| ISRCTN | ISRCTN16993271 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16993271 |
| EudraCT/CTIS number | 2014-004634-26 |
| ClinicalTrials.gov number | NCT03502291 |
| Secondary identifying numbers | 18994 |
- Submission date
- 02/09/2015
- Registration date
- 04/09/2015
- Last edited
- 21/10/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Secondary bacterial infections such as pneumococcal pneumonia are a leading cause of death during influenza epidemics. Individuals recently infected with influenza become more susceptible to pneumonia, an effect associated with an increased number of pneumococcus (bacteria causing pneumonia) in the nose (pneumococcal carriage) and uncontrolled inflammatory immunological responses. The interaction between influenza virus and pneumococcus has been known and well documented. Recent works have shown that the Live Attenuated Influenza Vaccine (LAIV) increases pneumococcal carriage in murine models (mice/rats). These results highlighted the potential effect of mass immunization of children with LAIV on pneumococcal carriage. Increased carriage could lead to increased pneumococcal disease in people vaccinated with LAIV as well as increased bacterial transmission within the population. LAIV has been licensed for use in children since 2011 in Europe, and has been increasingly administered in children and adults in the USA. This study looks at the effect of LAIV on pneumococcal carriage and compares it with the Quadrivalent Inactivated Influenza Vaccine (QIV).
Who can participate?
Adults aged 18-50, able to speak fluent English and able to give informed consent.
What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 are given Fluenz nasal vaccine (LAIV) and a placebo injection. Those in group 2 are given Fluarix vaccination (QIV) as an injection and a placebo nasal spray. All participants are inoculated with pneumococcal bacteria in the nose. Clinical symptoms and pneumococcal carriage between the two groups are then compared.
What are the possible benefits and risks of participating?
The benefit to volunteers when taking part in this study will be that they will all receive a flu vaccination. The risks associated with taking part in the study relate to the vaccination, inoculation with pneumococcus, blood sampling and nasal cell sampling. Risks associated with the influenza/ placebo vaccinations include: Pain and tenderness at the site of injection; Muscle aches; Fatigue; Nausea; Diarrhoea; Tiredness; Swelling at injection site; Headache; Runny, stuffy nose; Anaphylaxis (very rare 1: 1000000). Risks associated with blood sampling: feeling faint, bruising
Risks associated with pneumococcal inoculation: pneumococcal infection however this very unloikely, we have experienced inoculating over 400 volunteers and we have not had one case of pneumococcal infection. Risks associated with nasal cell sampling: minor temporary discomfort, irritation, eyes watering and minor bleeding.
Where is the study run from?
Royal Liverpool University Hospital (UK)
When is the study starting and how long is it expected to run for?
August 2015 to November 2017
Who is funding the study?
Bill and Melinda Gates Foundation (USA)
Who is the main contact?
Miss Angela Wright
Contact information
Scientific
Royal Liverpool University Hospital
Research & Development
4th Floor, Linda McCartney Centre
Prescot Street
Liverpool, Merseyside
L7 8XP
United Kingdom
Study information
| Study design | Randomised; Observational; Design type: Clinical Laboratory Study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | The effect of live attenuated inactivated influenza vaccine on experimental human pneumococcal carriage: a randomised controlled trial |
| Study acronym | LAIV and EHPC |
| Study objectives | This study looks at the effect of live attenuated inactivated influenza vaccine (LAIV) on pneumococcal carriage dynamics and compares it with the Quadrivalent Inactivated Influenza Vaccine (QIV). |
| Ethics approval(s) | NRES Northwest- Liverpool East REC, ref: 14/NW/1460 |
| Health condition(s) or problem(s) studied | Topic: Infectious diseases and microbiology; Subtopic: Infection (all Subtopics); Disease: Infectious diseases and microbiology |
| Intervention | 1. Influenza Vaccination: Volunteers are randomised to receive Fluenz nasal vaccine (LAIV) plus placebo injection OR Fluarix vaccination (QIV) via injection and placebo nasal spray 2. Pneumococcal Inoculation: All volunteers are inoculated with pneumococcal bacteria in the nose Study Entry : Single Randomisation only |
| Intervention type | Other |
| Primary outcome measure | 1. We will define the effect of LAIV on pneumococcal colonisation using the EHPC model in order to assess the potential effects of mass influenza vaccination. We will measure colonisation acquisition, density and duration. 2. Pneumococcal colonisation will be monitored using microbiological cultures of nasal wash samples. Nasal wash samples will be taken at pre-vaccination/ preinoculation*, day 2, 6*/7, 9, 14, 21*/22 and 27*/29 post inoculation in study one and study two*. |
| Secondary outcome measures | 1. To evaluate changes in commensal and potential pathogenic species in nasopharyngeal microbiome associated with influenza vaccination 2. To evaluate inflammatory responses at the nasal mucosa using mucosal nanosampling method (lining fluid and cells) 3. To evaluate cellular responses in the lung after LAIV and EHPC co-infection 4. To evaluate symptoms associated with influenza vaccination and EHPC |
| Overall study start date | 01/10/2014 |
| Completion date | 14/11/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 50 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 314; UK Sample Size: 314; Description: To allow for a dropout rate of 10%, up to 146 participants will be initially recruited for study 1 and up to 168 participants will be initially recruited for study 2.130 participants will complete the study (65 in each arm) to achieve 80% power to detect 50% increase in colonisation rates induced by antecedent LAIV compared to control 150 participants will complete the study (100 in LAIV arm and 50 in QIV arm) to achieve 99% power to detect a 2-fold increase in pneumococcal density induce |
| Key inclusion criteria | Participants will be eligible to participate in this study provided they: 1. Have capacity to give informed consent 2. Aged 18-50 yrs - ages chosen to minimise the risk of pneumococcal infection 3. Speak fluent English to ensure a comprehensive understanding of the research project and their proposed involvement, in order to minimise any communication issues to maximise participant safety |
| Key exclusion criteria | 1. Currently involved in another study unless observational or in follow-up phase (noninterventional) 2. Received any influenza vaccine in the last 2 years 3. Egg allergy (as per influenza vaccines patient leaflet) 4. Previous significant adverse reaction to any vaccination/immunisation 5. Close contact with at risk individuals (children under 5 years, immunosuppressed adults, elderly, chronic ill health) – to minimise risk of pneumococcal transmission and transmission of virus for those receiving the LAIV 6. Current regular smoker (smokes daily) 7. Significant smoking history [defined as someone who has previously smoked more than 20 cigarettes per day for 10 years or the equivalent (>10 pack yrs)] – to minimise risk of bronchoscopy or pneumococcal disease 8. Asthma (on regular medication) or respiratory disease – to minimise risk of bronchoscopy or pneumococcal disease 9. Pregnant to minimise the risk of pneumococcal disease 10. Women of childbearing potential (WOCBP) who are not deemed to have sufficient, effective birth control in place for 1 month prior to vaccination and 1 month after the final vaccination 11. Allergic to penicillin/amoxicillin/ gentamicin 12. On medication that may affect the immune system in any way e.g. steroids, steroid nasal spray 13. Are regularly taking acetylsalicylic acid (aspirin) – as per LAIV guidance to reduce the risk of Reye’s syndrome 14. Been involved in a clinical trial involving EHPC over the last 3 years 15. Unable to give fully informed consent 16. Current acute severe febrile illness - to avoid vaccination and inoculation in participants that may have current infection |
| Date of first enrolment | 26/08/2015 |
| Date of final enrolment | 30/04/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
4th Floor, Linda McCartney Centre
Prescot Street
Liverpool, Merseyside
L7 8XP
United Kingdom
Sponsor information
Hospital/treatment centre
The Walton Centre for Neurology and Neurosurgery
Prescot Street
Liverpool
L7 8XP
England
United Kingdom
"ROR" |
https://ror.org/009sa0g06 |
|---|
Funders
Funder type
Government
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | We plan to publish the results in peer reviewed journals and at International conferences. We will aim to publish the results from study one and study two at the end of study two. We will make the publication available to participants at the end of the study. We will also disseminate research findings to the participants at the end of the study in the form of a newsletter. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
21/10/2019: Added EudraCT link to basic results (scientific)
18/07/2019: ClinicalTrials.gov number added.
