A Double-Blind, Randomized, Controlled Trial to Evaluate the Safety, Immunogenicity, and Efficacy of Standard Dose Quadrivalent Inactivated Influenza Vaccine, and Double Dose Quadrivalent Inactivated Influenza Vaccine in HIV-Infected and HIV-Uninfected Pregnant Women in a Malaria-Endemic Area of Rural Western Kenya
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Proportion of women with an appropriate rise in Hemagglutination Inhibition (HI) titers
研究概览
简要总结
In 2012, the WHO Strategic Advisory Group of Experts (SAGE) concluded that pregnant women are the most important risk group for season influenza vaccination based upon "compelling evidence of substantial risk of severe disease in this group and evidence that seasonal influenza vaccine is safe and effective in preventing disease in pregnant women as well as their young infants, in whom disease burden is also high". Recent data from Kenya, similarly suggest rates of influenza-associated hospitalizations in children under age 1 to be as high, or higher, than those observed in the United States. However, TIV may have reduced immunogenicity in HIV-infected adults, and HIV infection has been shown to reduce placental transfer of both tetanus and measles antibodies. Therefore, we propose to conduct a double-blind randomized controlled trial of influenza vaccines stratified by HIV status in up to 720 pregnant women in their second and third trimesters and their infants residing in health and demographic surveillance sites (HDSS) in Nyanza Province, Western Kenya. We propose to assess the safety, immunogenicity, and efficacy of standard dose QIV and double dose QIV in HIV-infected and HIV-uninfected pregnant women. Findings will inform maternal influenza vaccination policies in Kenya and other African countries.
详细描述
Recent investments in influenza surveillance in many African countries confirm results from other countries that young children, pregnant women, and those with chronic medical conditions are at increased risk of hospitalization and death from influenza infection. Annual influenza vaccination is the most effective method for preventing influenza virus infection and its complications. Vaccination is currently recommended in high risk groups in many developed countries and the WHO Strategic Advisory Group of Experts (SAGE) on Immunization made a recommendation for vaccination of pregnant women in their 2005 position paper on influenza vaccine. In 2012, the SAGE further concluded that pregnant women are the most important risk group for inactivated seasonal influenza vaccination based upon "compelling evidence of substantial risk of severe disease in this group and evidence that seasonal influenza vaccine is safe and effective in preventing disease in pregnant women as well as their young infants, in whom disease burden is also high".
Maternal influenza immunization is viewed as the most effective way to protect infants less than 6 months of age who are not yet eligible for immunization. In the United States, children under 6 months experience very high rates of influenza-associated hospitalization and are among those most at risk of severe outcomes. Recent data from Kenya, similarly suggest rates of influenza-associated hospitalizations in children under age 1 to be as high, or higher, than those observed in the United States. Vaccination of pregnant women provides protection to their infants against laboratory-confirmed influenza illness in the first months of life. Furthermore, vaccination of pregnant women has been associated with a decreased risk of pre-term birth and small for gestational age in Canada and the state of Georgia in the US, and increased birth weight in infants during periods of high transmission in Bangladesh. However, traditional TIV may have reduced immunogenicity in HIV-infected adults, and HIV infection has been shown to reduce placental transfer of both tetanus and measles antibodies. The high prevalence of other diseases, including malaria and malnutrition, may also impact the effectiveness of influenza vaccination for pregnant women and their infants in sub-Saharan Africa.
Use of double dose QIV may produce a greater immune response in pregnant women and increased antibody production may improve transplacental transfer of influenza antibodies to the developing fetus, conferring a better or possibly longer duration of protection from influenza infection. Therefore, we propose to conduct a randomized controlled trial of influenza vaccines in a high HIV-prevalence, malaria-endemic setting in Kenya, using inactivated polio vaccine (IPV) as a comparator/control. We propose to assess the safety, immunogenicity, and efficacy of standard dose (15 µg) QIV (FLUARIX® (GlaxoSmithKline Biologicals, Dresden, Germany) and double dose (30 µg) QIV in HIV-infected and HIV-uninfected pregnant women.
OBJECTIVES:
- To evaluate the immunogenicity of standard dose (15 µg) QIV and double dose (30 µg) QIV in HIV-infected and uninfected pregnant women
- To evaluate the level of vaccine-induced influenza antibody transfer to infants of HIV-infected and uninfected pregnant women who receive standard dose (15 µg) QIV or double dose (30 µg) QIV
- To evaluate the safety of standard dose (15 µg) QIV and double dose (30 µg) QIV in HIV-infected and HIV-uninfected pregnant women and fetus
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
- 13 Years 至 49 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Resident of HDSS village
- •Singleton pregnancy
- •Second or third trimester (after quickening) but before 33 weeks of gestation by fundal height
- •Does not plan to relocate out of the HDSS area or population-based surveillance site in the next 12 months and agrees to all follow-up visits/contact by phone
- •Is not currently enrolled in another intervention study
- •Provides informed consent by signature or thumb print
- •Consents to HIV testing and counseling as required
- •Willing to deliver in the labor ward of the study hospital
- •No history of chronic illness requiring multiple hospitalizations or prolonged medical therapy (except HIV on ART)
排除标准
- •History of allergic reaction to any component of the study vaccines
- •Residence outside the study area or planning to relocate out in the 9 months following enrollment
- •Received immunoglobulin or blood products within 45 days of study entry
- •Used immunosuppressive medication within 45 days of study entry (inhaled and topical corticosteroids permitted)
- •High risk pregnancy including any pre-existing condition likely to cause complications of pregnancy (hypertension, diabetes, current asthma, eclampsia or pre-eclampsia, epilepsy, heart disease, renal disease, liver disease, fistula repair, leg or spine deformity)
- •Unable to give informed consent (for example due to mental disability)
- •Previous enrollment in a study with similar interventions
- •Gestational age >32 weeks by last menstrual period or fundal height
- •Acutely ill with temperature ≥37.5°C on the day of randomization/vaccination
- •Hemoglobin <7.0 g/dL
- •Influenza vaccination in previous 12 months
结局指标
主要结局
Proportion of women with an appropriate rise in Hemagglutination Inhibition (HI) titers
时间窗: Enrollment (Day 0) vs. Day 28 for each study arm
The proportion of standard dose (15 µg) QIV and double dose (30 µg) QIV recipients with a fourfold rise in HI titers or HI titers ≥40 if baseline HI titer \<10 compared to the same proportion in controls
Proportion of infants born to standard dose (15 µg) QIV and double dose (30 µg) QIV recipients with HI titers greater than or equal to 40 in cord blood compared to same in controls.
时间窗: At delivery
Number of solicited and unsolicited adverse events post-vaccination by study arm
时间窗: During follow-up period, approx. 9 months
次要结局
- Vaccine efficacy of standard dose (15 µg) QIV and double dose (30 µg) QIV in mothers and infants compared to control mothers and infants.(Entire follow-up period, approx. 9 months)
- HIV infection and placental antibody transfer(Delivery)
- Birth weight(Delivery)
- Peripheral and placental parasitemia impact on vaccination(Day 0 and delivery)
- baseline polio immunity and polio antibody transfer(day 0 and delivery)