Standard Versus High Dose Inactivated Influenza Vaccine in RA

NCT ID: NCT02936180

Last Updated: 2024-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 279 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2018-12-31

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Standard dose influenza vaccine

Patients will receive one dose of FLUZONE® Standard Dose Quadrivalent Inactivated Influenza Vaccine (SD-QIV)

Group Type: ACTIVE_COMPARATOR

SD-QIV

Intervention Type: BIOLOGICAL

High dose influenza vaccine

Patients will receive one dose of FLUZONE® High Dose Trivalent Inactivated Influenza Vaccine (HD-TIV)

Group Type: ACTIVE_COMPARATOR

HD-TIV

Intervention Type: BIOLOGICAL

Interventions

HD-TIV

Intervention Type: BIOLOGICAL

SD-QIV

Intervention Type: BIOLOGICAL

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Arthritis Society, Canada

OTHER

Sponsor Role: collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Ines Colmegna

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ines Colmegna, MD

Role: PRINCIPAL_INVESTIGATOR

McGill University Health Centre/Research Institute of the McGill University Health Centre

Locations

McGill University Health Centre

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 38258270 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://doi.org/10.1016/S2665-9913(19)30094-3

Publication

Other Identifiers

MP-37-2017-2773

Identifier Type: -

Identifier Source: org_study_id