Comparison of High vs. Standard Dose Influenza Vaccines in Adult Solid Organ Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 396
- 试验地点
- 1
- 主要终点
- The number of participants reporting solicited injection site reactions and systemic reactions.
研究概览
简要总结
The influenza virus is a significant cause of morbidity in adult solid organ transplant (SOT) recipients. However, these individuals show a suboptimal response to vaccines including the standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. The first study compared HD-IIV vs. SD-IIV in adult SOT and noted HD-IIV was safe and reported higher immunogenicity; however, the median post-transplant period was 38 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV a month apart compared to one-dose SD-IIV revealed increased immunogenicity, with a median post-transplantation period of 18 months. Therefore, these studies lack evaluation in the early post-transplantation period in this vulnerable population when influenza disease is most severe. The administration of two-doses of HD-IIV in the same influenza season has also not been studied in SOT recipients. Moreover, the vast majority of SOT influenza vaccinations studies have not substantively evaluated prolonged immunogenicity. Thus, the optimal immunization strategy for SOT recipients less than 12 months post-transplant is poorly-defined. In addition, the immunologic predictors and correlates of influenza vaccine immunogenicity in SOT recipients have not been defined. The investigators hypothesize that adult solid organ transplant recipients that are 1-11 months out from transplant and are receiving high-dose inactivated influenza vaccine will have higher hemagglutination inhibition (HAI) geometric mean titers to influenza A antigens compared to adult SOT recipients receiving standard-dose inactivated influenza vaccine. To test this hypothesis and address the above critical knowledge gaps, The investigators propose to conduct a phase II multicenter randomized controlled trial comparing either two doses HD-IIV, two doses of SD-IIV, or one-dose of HD-IIV in adult kidney, heart, and liver SOT recipients 1-11 months post-transplantation. The results of this study will address significant gaps in knowledge regarding influenza vaccine strategies and immune responses in adult SOT recipients and will guide vaccine recommendations in this vulnerable population.
详细描述
Study Design. The proposed study is a multi-center, phase II, randomized, controlled, immunogenicity and safety trial comparing two doses of the trivalent HD-IIV vs. two doses of the quadrivalent SD-IIV vs. one dose of HD-IIV followed by one dose of placebo in adult SOT recipients (kidney, heart, and liver)
Primary and Secondary Objectives
I. Primary:
Immunogenicity Objective To compare the hemagglutination inhibition (HAI) geometric mean titers (GMT) to influenza A antigens in adult SOT recipients after receiving either one dose of high dose quadrivalent influenza vaccine (HD-QIV), two doses of standard dose (SD)-QIV, or two doses of HD-QIV over one influenza season.
Safety Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult SOT recipients who have undergone kidney, heart, and/or liver transplantation I. Multiple organ recipients are permitted (i.e. any combination of organs including kidney, heart and/or liver).
- •II. Subjects undergoing re-transplantation are permitted
- •Age ≥18 years at vaccination
- •≥1 month and <12 months post-SOT
- •Anticipated to be available for duration of study
- •Can be reached by telephone, email, or text message
排除标准
- •History of severe hypersensitivity to previous influenza vaccination or anaphylaxis to eggs/egg protein
- •History of Guillain-Barre syndrome
- •History of known active infection with HIV
- •History of known severe latex hypersensitivity
- •History of receiving the current season's influenza vaccine post-transplant prior to enrollment in the study
- •Pregnant female
- •Proven influenza disease after September 1st and before first study vaccine (patient can still receive the second influenza vaccination despite proven influenza disease once enrolled)
- •History of lung or intestine transplant
- •CMVIG/IVIG/SCIG receipt in the 28 days prior to or planned administration within 84-126 days of the calendar date of first vaccination
- •Subjects must have a platelet count of <20,000 to receive the immunizations
研究组 & 干预措施
Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine
two doses of 0.7 mL HD-IIV (60µg of each influenza antigen) 28-42 days apart
干预措施: High Dose Quadrivalent Inactivated Influenza Vaccine (Biological)
Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine
two doses of 0.5 mL SD-IIV (15µg of each influenza antigen) 28-42 days apart
干预措施: Standard Dose Quadrivalent Inactivated Influenza Vaccine (Biological)
One Dose High Dose Quadrivalent Inactivated Influenza Vaccine
one dose of 0.7 mL HD-IIV (60µg of each influenza antigen) followed by placebo 28-42 days later
干预措施: High Dose Quadrivalent Inactivated Influenza Vaccine (Biological)
结局指标
主要结局
The number of participants reporting solicited injection site reactions and systemic reactions.
时间窗: Within 7 days post-vaccination
Post-vaccination local adverse events (pain, tenderness, swelling/induration, erythema/redness, swelling/induration size, and erythema/redness size) and systemic adverse events (Fatigue/malaise, headache, nausea, body ache/myalgia (not at the injection site), general activity level, vomiting, and fever).
Geometric Mean Titers of influenza vaccine antibodies.
时间窗: Day 56 (post-vaccination)
Antibody titers will be measured by hemagglutination inhibition assay.
次要结局
- Geometric Mean Titers Ratio of influenza vaccine antibodies (post-/pre-vaccination).(Day 56 (post-vaccination))
- The number of participants achieving seroprotection and seroconversion for influenza virus.(Day 56 (post-vaccination))
研究者
Natasha Halasa
Principal Investigator, Professor of Pediatric Infectious Diseases
Vanderbilt University Medical Center