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

Primary Purpose

Rheumatoid Arthritis

Status
Unknown status
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
HD-TIV
SD-QIV
Sponsored by
McGill University Health Centre/Research Institute of the McGill University Health Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Flu vaccine, Influenza

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • McGill University Health Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Standard dose influenza vaccine

High dose influenza vaccine

Arm Description

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

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

Outcomes

Primary Outcome Measures

Seroconversion rate to HD- versus SD-IV in people with RA
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.
Seroprotection rate to HD- versus SD-IV in people with RA
Seroprotection rate (SPR): the proportion of subjects in a given treatment group attaining a reciprocal HI titre of ≥1:40 at D28 post-vaccination.
Seroconversion factor in people with RA who received HD- versus SD-IV
Seroconversion factor or GMFR: the geometric mean of the ratio of GMTs (D28/ D0).
Geometric mean titres (GMTs) of HI in people with RA who received HD- versus SD-IV
Geometric mean titres (GMTs) of HI at D0 and D28.

Secondary Outcome Measures

Durability of HI antibody responses for SD- and HD- IV.
Rates of side effects during the surveillance period in SD- and HD-IV.

Full Information

First Posted
October 7, 2016
Last Updated
August 14, 2018
Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators
The Arthritis Society, Canada
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1. Study Identification

Unique Protocol Identification Number
NCT02936180
Brief Title
Standard Versus High Dose Inactivated Influenza Vaccine in RA
Acronym
IV-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

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Unknown status
Study Start Date
October 2016 (undefined)
Primary Completion Date
July 2018 (Actual)
Study Completion Date
December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborators
The Arthritis Society, Canada

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, Flu vaccine, Influenza

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
280 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard dose influenza vaccine
Arm Type
Active Comparator
Arm Description
Patients will receive one dose of FLUZONE® Standard Dose Quadrivalent Inactivated Influenza Vaccine (SD-QIV)
Arm Title
High dose influenza vaccine
Arm Type
Active Comparator
Arm Description
Patients will receive one dose of FLUZONE® High Dose Trivalent Inactivated Influenza Vaccine (HD-TIV)
Intervention Type
Biological
Intervention Name(s)
HD-TIV
Intervention Type
Biological
Intervention Name(s)
SD-QIV
Primary Outcome Measure Information:
Title
Seroconversion rate to HD- versus SD-IV in people with RA
Description
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.
Time Frame
Day 28
Title
Seroprotection rate to HD- versus SD-IV in people with RA
Description
Seroprotection rate (SPR): the proportion of subjects in a given treatment group attaining a reciprocal HI titre of ≥1:40 at D28 post-vaccination.
Time Frame
Day 28
Title
Seroconversion factor in people with RA who received HD- versus SD-IV
Description
Seroconversion factor or GMFR: the geometric mean of the ratio of GMTs (D28/ D0).
Time Frame
Day 28
Title
Geometric mean titres (GMTs) of HI in people with RA who received HD- versus SD-IV
Description
Geometric mean titres (GMTs) of HI at D0 and D28.
Time Frame
Day 0 and Day 28
Secondary Outcome Measure Information:
Title
Durability of HI antibody responses for SD- and HD- IV.
Time Frame
Day 186
Title
Rates of side effects during the surveillance period in SD- and HD-IV.
Time Frame
Day 28
Other Pre-specified Outcome Measures:
Title
Performance of the micro-neutralization assay in comparison to the HI assay.
Time Frame
Day 186
Title
Rates of health care use in patients receiving SD- or HD-IV.
Time Frame
Day 186

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of seropositive RA (rheumatoid factor (RF) and/or anti-CCP antibody positive) based on the 2010 ACR-EULAR criteria. At least 6 months of treatment including anti-TNF agents, abatacept, rituximab (dose received within the previous 6 months) and/or methotrexate. Informed consent form signed and dated. Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: Vaccination against influenza in the 6 months preceding the trial vaccination. 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. History of Guillain-Barré syndrome within six weeks of a previous influenza vaccination. Dementia or any other cognitive condition that could interfere with the trial procedures. Thrombocytopenia or bleeding disorder contraindicating IM vaccination (according to treating rheumatologist). Current alcohol abuse or drug addiction. 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. Signs and symptoms of an acute infectious respiratory illness. If this exists, vaccination will be deferred until the symptoms resolve. 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)
Facility Information:
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Standard Versus High Dose Inactivated Influenza Vaccine in RA

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