Clinical trial NCT02936180: Standard Versus High Dose Inactivated Influenza Vaccine in RA
Official title: Improving Influenza Immunization Responses in Rheumatoid Arthritis: A Strategy To Enhance Protection Against A Preventable Cause Of Death In An At Risk Population?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Flu vaccine
Influenza
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: The Arthritis Society, Canada
First posted: 2016-10-18
Enrollment: 279
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Patients with rheumatoid arthritis have increased risk of seasonal influenza and influenza-related complications but have reduced vaccine immunogenicity. It is unknown whether patients with rheumatoid arthritis would benefit from more immunogenic vaccine formulations. This study investigated the immunogenicity and safety of a high-dose trivalent inactivated influenza vaccine (HD-TIV) in patients with rheumatoid arthritis compared to a standard-dose quadrivalent influenza vaccine (SD-QIV).

Detailed description: Influenza, a vaccine-preventable respiratory disease, is ranked 8th among the causes of death in the Canadian population. Among rheumatoid arthritis (RA) patients, the incidence of both seasonal influenza and serious influenza-related illness (IRI) are increased. Despite being a high priority group targeted for vaccination, the diagnosis of RA and other patient-specific factors (i.e. older age, treatment, current smoking) are linked to impaired vaccination responses.

Thus the burden of influenza among people with RA is disproportionally high, and interventions to improve responses to influenza vaccination are urgently needed. Strategies to optimize protection in another vulnerable group, the elderly, include the use of quadrivalent vaccines, higher antigen doses, and adjuvants. A high-dose, trivalent, inactivated influenza vaccine (HD-TIV) has recently been shown to have a similar safety profile to standard dose vaccine (SD-TIV) with improved immunogenicity and protection in adults ≥65 years of age. Whether or not analogous strategies to improve responses to influenza vaccine will enhance protection in people with RA is unknown. The investigators hypothesize that the use of the HD-influenza vaccine will improve vaccine-induced protection (i.e. seroconversion and seroprotection) in people with RA compared to SD-influenza vaccine. The investigators propose to conduct a stratified, randomized, modified double blind, active-controlled trial to assess immune responses to two commercial influenza vaccines containing different antigen doses in individuals with RA.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of seropositive RA (rheumatoid factor (RF) and/or anti-CCP antibody positive) based on the 2010 ACR-EULAR criteria.
2. At least 6 months of treatment including anti-TNF agents, abatacept, rituximab (dose received within the previous 6 months) and/or methotrexate.
3. Informed consent form signed and dated.
4. Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

1. Vaccination against influenza in the 6 months preceding the trial vaccination.
2. Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to TIV or to a vaccine containing any of the same substances.
3. History of Guillain-Barré syndrome within six weeks of a previous influenza vaccination.
4. Dementia or any other cognitive condition that could interfere with the trial procedures.
5. Thrombocytopenia or bleeding disorder contraindicating IM vaccination (according to treating rheumatologist).
6. Current alcohol abuse or drug addiction.
7. Moderate or severe acute illness with or without fever. If this exists, vaccination will be deferred until the individual has been medically stable and/or afebrile for at least 24 hours.
8. Signs and symptoms of an acute infectious respiratory illness. If this exists, vaccination will be deferred until the symptoms resolve.
9. Pregnant women (the rationale for excluding this group is not their lack of indication for vaccination but the changes of maternal immune responses during pregnancy)

Primary outcomes:
measure: Seroconversion Rate to HD- Versus SD-IV in People With RA
timeFrame: Day 28
measure: Seroprotection Rate to HD- Versus SD-IV in People With RA
timeFrame: Day 28
measure: Geometric Mean Titres (GMTs) of HI in People With RA Who Received HD- Versus SD-IV
timeFrame: Day 28
Secondary outcomes:
measure: Durability of Detectable Levels of HI Antibody for SD- and HD- IV.
timeFrame: Day 186
measure: Rates of Side Effects During the Surveillance Period in SD- and HD-IV.
timeFrame: Day 28
Other outcomes:
measure: Performance of the Micro-neutralization Assay in Comparison to the HI Assay.
timeFrame: Day 186
measure: Rates of Health Care Use in Patients Receiving SD- or HD-IV.
timeFrame: Day 186
Locations:
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Ines Colmegna, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Colmegna I, Useche ML, Rodriguez K, McCormack D, Alfonso G, Patel A, Ramanakumar AV, Rahme E, Bernatsky S, Hudson M, Ward BJ. Immunogenicity and safety of high-dose versus standard-dose inactivated influenza vaccine in rheumatoid arthritis patients: a randomised, double-blind, active-comparator trial. Lancet Rheumatol. 2020 Jan;2(1):e14-e23. doi: 10.1016/S2665-9913(19)30094-3. Epub 2019 Nov 20.