Standard Versus High Dose Inactivated Influenza Vaccine in RA (IV-RA)

August 12, 2024 updated by: Ines Colmegna, McGill University Health Centre/Research Institute of the McGill University Health Centre

Improving Influenza Immunization Responses in Rheumatoid Arthritis: A Strategy To Enhance Protection Against A Preventable Cause Of Death In An At Risk Population?

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

279

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill University Health Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard dose influenza vaccine
Patients will receive one dose of FLUZONE® Standard Dose Quadrivalent Inactivated Influenza Vaccine (SD-QIV)
Biological: SD-QIV
Active Comparator: High dose influenza vaccine
Patients will receive one dose of FLUZONE® High Dose Trivalent Inactivated Influenza Vaccine (HD-TIV)
Biological: HD-TIV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Seroconversion Rate to HD- Versus SD-IV in People With RA
Time Frame: Day 28
Seroconversion rate (SCR): proportion of subjects in a given treatment group (SD- or HD) with either a ≥4-fold increase in reciprocal HI titres between D0 and D28 or a rise of undetectable HI titre (i.e. <1:10) pre-vaccination (D0) to an HI titre of ≥1:40 at D28 post vaccination.
Day 28
Seroprotection Rate to HD- Versus SD-IV in People With RA
Time Frame: Day 28
Seroprotection rate (SPR): the proportion of subjects in a given treatment group attaining a reciprocal HI titre of ≥1:40 at D28 post-vaccination.
Day 28
Geometric Mean Titres (GMTs) of HI in People With RA Who Received HD- Versus SD-IV
Time Frame: Day 28
Geometric mean titres (GMTs) of HI at D28.
Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Durability of Detectable Levels of HI Antibody for SD- and HD- IV.
Time Frame: Day 186
Number of participants with detectable HI antibodies at Day 186
Day 186
Rates of Side Effects During the Surveillance Period in SD- and HD-IV.
Time Frame: Day 28
Number of Participants with Side Effects
Day 28

Other Outcome Measures

Outcome Measure
Time Frame
Performance of the Micro-neutralization Assay in Comparison to the HI Assay.
Time Frame: Day 186
Day 186
Rates of Health Care Use in Patients Receiving SD- or HD-IV.
Time Frame: Day 186
Day 186

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Collaborators

The Arthritis Society, Canada

Investigators

  • Principal Investigator: Ines Colmegna, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2016

Primary Completion (Actual)

July 1, 2018

Study Completion (Actual)

December 1, 2018

Study Registration Dates

First Submitted

October 7, 2016

First Submitted That Met QC Criteria

October 14, 2016

First Posted (Estimated)

October 18, 2016

Study Record Updates

Last Update Posted (Actual)

August 13, 2024

Last Update Submitted That Met QC Criteria

August 12, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MP-37-2017-2773

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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