Comparison of High Dose vs. Standard Dose Influenza Vaccines in Lung Allograft Recipients
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 270
- 试验地点
- 2
- 主要终点
- The number of participants reporting solicited injection site reactions and systemic reactions.
研究概览
简要总结
Lung allograft recipients have a higher burden of influenza disease and greater associated morbidity and mortality compared with healthy controls. Induction and early maintenance immunosuppression is thought to impair immunogenicity to standard dose inactivated influenza vaccine. This early post-transplant period is when immunity is most desirable, since influenza disease during this time frame is associated with adverse consequences. Thus, strategies to reduce severe influenza disease in this highly susceptible population are critical. No trials in lung transplant recipients have evaluated two doses of HD-IIV within the same influenza season as a strategy to improve immunogenicity and durability of influenza prevention. Furthermore, no influenza vaccine trials have focused on enrollment of subjects at early post-transplant timepoints. Very few studies have been performed in solely lung allograft recipients. Immunosuppression intensity is highest in lung patients, thereby limiting comparisons to recipients of heart, liver, and kidney transplants. Therefore, studies to assess both HD-IIV and two-dose strategies in the same influenza season in post-lung transplant recipients are greatly needed.
The central hypothesis of our proposal is that lung allograft recipients who are 1-35 months post-transplant and receiving two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have higher HAI geometric mean titers (GMT) to influenza antigens compared to those receiving two doses of SD-QIV. To test this hypothesis and address the above critical knowledge gaps, we propose to conduct a phase II, multi-center, randomized, double-blind, controlled immunogenicity and safety trial comparing the administration of two doses of HD-QIV to two doses of SD-QIV in lung allograft recipients 1-35 months post-transplant. The results of this clinical trial will address significant knowledge gaps regarding influenza vaccine strategies (e.g., one vs. two doses and HD-QIV vs. SD-QIV) and immune responses in lung transplant recipients and will guide vaccine recommendations during the post-transplant period.
详细描述
Study Design: The proposed study is a phase II, multi-center, double-blind, randomized controlled immunogenicity and safety trial comparing two doses of HD-QIV to two doses of SD-QIV in lung allograft recipients.
- Hypothesis 1: We hypothesize that lung allograft recipients 1-35 months post-transplant who receive two doses of HD-QIV will develop higher HAI GMTs to influenza antigens compared to lung allograft recipients receiving two doses of SD-QIV.
Specific Aim 1: To compare the HAI GMTs to influenza antigens in lung allograft recipients after receiving either two doses of HD-QIV or two doses of SD-QIV. 2. Hypothesis 2: We hypothesize that administration of two doses of HD-QIV in lung transplant recipients will be well tolerated and the safety profile will be similar to two doses of SD-QIV with regard to solicited local and systemic side effects.
Specific Aim 2: To compare the frequency and severity of solicited local and systemic adverse events in lung allograft recipients after receiving either two doses of HD-QIV or two doses of SD-QIV. 3. Hypothesis 3: We hypothesize that baseline immunophenotypic markers of exhaustion, immune senescence, and immune activation at the pre-vaccine timepoint will correlate with post-vaccine HAI titers.
Specific Aim 3: To define the relationship between baseline phenotypes of T- and B-cell subsets, T-cell activation and post-vaccination HAI titers among lung allograft recipients receiving either two doses of HD-QIV or two doses of SD-QIV.
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)
盲法说明
All study staff, and subjects will be blinded to which vaccine the subject will receive, except for an un-blinded vaccinator. This individual will not inform the study team or the subjects which vaccine they administered to the subject. The un-blinded vaccinator will not participate in any other study activities. If the study vaccine is provided in a blinded manner, then research staff will be able to administer the vaccine, and an un-blinded vaccinator will not be necessary. The pharmacy will be un-blinded and will have a record of which vaccine was given to each subject.
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Lung allograft recipients
- •Age ≥16 years at time of enrollment
- •≥1 month (30 days) and <36 months post-lung transplant
- •Anticipated to be available for duration of the study
- •Can be reached by telephone, email, or text message
排除标准
- •Recipient of multi-organ, extra-pulmonary, and/or hematopoietic stem cell transplant
- •Recipient of a re-do lung transplant
- •History of severe hypersensitivity to previous influenza vaccination or anaphylaxis to eggs/egg protein
- •History of Guillain-Barre syndrome
- •HIV positive patients, by history or documentation from previous test
- •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)
- •CMVIG/IVIG/SCIG receipt within 28 days of each vaccine
- •Receipt of rituximab or other B-cell depleting antibody (including proteasome inhibitors) therapy within 3-months of 1st study vaccine (Day 0).
- •Receipt of augmented T-cell depleting therapy within 3-months of 1st study vaccine (Day 0)
- •Investigator concern about study participation
研究组 & 干预措施
Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine
receive two doses of SD-QIV (0.5 mL; 15µg of each influenza antigen) 28-42 days apart
干预措施: Standard Dose Quadrivalent Inactivated Influenza Vaccine (Biological)
Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine
two doses of HD-QIV (0.7 mL; 60µg of each influenza antigen) 28-42 days apart
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
- The number of participants achieving seroprotection and seroconversion for influenza virus.(Day 56 (post-vaccination))
- Geometric Mean Titers Ratio of influenza vaccine antibodies (post-/pre-vaccination).(Day 56 (post-vaccination))
研究者
Natasha Halasa
Professor of Pediatric Infectious Diseases
Vanderbilt University Medical Center