Early Flu Shots in SOT

Safety and Immunogenicity of Influenza Vaccine During the First Post-Transplant Year in Solid Organ Transplant Recipients

Although time from transplant has been a factor in vaccine response, there is limited data on immunizations that occur in the first post-transplant year, and there are no data that suggest influenza vaccination early post-transplant may have any adverse effects on the graft. It is suggested that early vaccinations may lead to reduced immunogenicity due to induction immunosuppression. However, not vaccinating patients may leave them vulnerable to influenza infection for a period of time. This study is designed to look at the immunogenicity and side effects of the standard of care influenza vaccine in patients between 31 and 365 days post-transplant.

Study Overview

• Status: Withdrawn
• Conditions: Influenza; Solid Organ Transplant
• Intervention / Treatment: Biological: standard of care influenza vaccine

Detailed Description

Influenza virus is an important cause of morbidity in the transplant population and can lead to viral and bacterial pneumonia. Influenza vaccine is effective in the prevention of influenza infection and is recommended by the Canadian National Advisory Committee on Immunization (NACI). The annual influenza vaccine is suggested for transplant patients as the standard of care starting from 3 months post-transplant. Most recent guidelines now suggest that it is reasonable to get a flu shot starting earlier at 1 month post-transplant. Anti-rejection drugs are now tapered more quickly and it is possible that antibodies will be produced against the flu shot as early as 1 month post-transplant. The study hypothesizes that kidney and liver transplant recipients in the early post-transplant period (31-180 days) will have similar immunogenicity as those in the late post-transplant period (>180 days).

• Study Type: Observational

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2N2
      • University Health Network, Toronto General Hospital, Multi-Organ Transplant

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult solid organ transplant recipients between 31 and 365 days post-transplant.

Description

Inclusion Criteria:

• Kidney, liver or pancreas transplant recipients on at least one immunosuppressive medication
• Age ≥ 18
• Outpatient status
• Greater than 30 days post-transplant

Exclusion Criteria:

• Has already received influenza vaccination for 2017-2018 season
• Egg allergy or allergy to previous influenza vaccine
• Febrile illness in the past one week
• Active Cytomegalovirus viremia
• Use of Rituximab in the past one year
• Ongoing or recent (in past 30 days) therapy for acute rejection
• Chronic kidney insufficiency (creatinine clearance ≤30mL/min or dialysis-dependent
• Previous life-threatening reaction to influenza vaccine (i.e., Guillain Barre Syndrome)
• Receipt of intravenous immunoglobulin (IVIG) in the past 30 days or planning to receive IVIG in the next four weeks

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
31-90 days; Patient 31-90 days after transplantation receiving standard of care annual 2017-2018 influenza vaccine.	Biological: standard of care influenza vaccine; The standard of care annual 2017-2018 influenza vaccine will be used for this study.; Other Names: annual influenza vaccine
91-180 days; 91-180 days after transplantation receiving standard of care annual 2017-2018 influenza vaccine.	Biological: standard of care influenza vaccine; The standard of care annual 2017-2018 influenza vaccine will be used for this study.; Other Names: annual influenza vaccine
181-365 days; 181-365 days after transplantation receiving standard of care annual 2017-2018 influenza vaccine.	Biological: standard of care influenza vaccine; The standard of care annual 2017-2018 influenza vaccine will be used for this study.; Other Names: annual influenza vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine immunogenicity	Vaccine immunogenicity based on assessment of pre- and post-vaccine (4 weeks) antibody titer. A positive vaccine response will be defined based on: Seroconversion rate: serological response with a four-fold or greater increase in HAI antibody titers to each of the three antigens in the vaccine, and; Seroprotection rate: HAI titers of ≥1:40 to each of the three antigens post-immunization.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety- adverse events	Local and systemic adverse events to vaccination	7 days
Safety- graft rejection	Rates of biopsy proven allograft rejection in the 6 months following vaccination	6 months
Safety- HLA	Development of de novo or increased titer of HLA alloantibody and specifically DSA (donor specific antibody). The 4 weeks post-vaccine sample will be compared with the pre-vaccine samples.	4 weeks
Vaccine efficacy- CMI	Analysis of CMI in a subgroup of 60 patients (influenza strain-specific CD4+ and CD8+ T-cell responses; detectable vs. non-detectable and absolute percentage) at four weeks post-vaccine vs. pre-vaccine sample. CMI responses will also be correlated with HAI responses.	4 weeks
Vaccine efficacy- infection	Documented influenza infection (i.e., microbiology proven by the direct fluorescent antibody, viral culture, or PCR) in the six months following vaccination.	6 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Deepali Kumar, MD, UHN

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2019
• Primary Completion (Actual): May 7, 2019
• Study Completion (Actual): May 7, 2019

Study Registration Dates

• First Submitted: October 27, 2017
• First Submitted That Met QC Criteria: October 27, 2017
• First Posted (Actual): November 1, 2017

Study Record Updates

• Last Update Posted (Actual): October 20, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: vaccine immunogenicity; vaccine safety
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 17-5960

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No