Comparison of Immunity Following Inactivated Poliovirus Vaccine Versus Fractional Dose Inactivated Poliovirus Vaccine: a Community Based Randomized Controlled Trial in Pakistan
试验速览
- 阶段
- 4 期
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- sero-conversion defined as the change from seronegative to seropositive (from reciprocal titer of <8 to >8)
研究概览
简要总结
This study will be conducted in four low-income areas of Bin Qasim Town Karachi. This will be a community based randomized control trial of 21 months duration. The trial will include four arms; arm A and B will enroll children age 14-18 weeks and randomize them to either full dose IPV (0.5ml) or fractional IPV (0.1ml). Arms C and D will enroll children at 9 months of age and randomize them to either fractional or full dose IPV.
Children aged 14 weeks for arms A and B and 9 months for arms C and D living in the selected communities of Bin qasim Town Karachi who have not received IPV vaccine during routine immunization for arms A and B and who have documentary evidence of receiving IPV vaccine at 14 weeks of age for arms C and D will be eligible for enrollment.
The investigators will exclude children who are found acutely ill or those requiring emergent medical care/hospitalization at the time of enrollment.
The investigators will use the Demographic Surveillance System (DSS) in the four study areas to identify the households with eligible children. The children of the parents who agree to participate in the study will be screened for eligibility by the trained research associates. After randomization into four different arms, the study trained research vaccinators will administer the IPV or fIPV as per randomization. Children will be observed in the center for 30 minutes after vaccination before leaving for home. Parents/guardians of all the participants will also be requested to immediately report any adverse effect occurring later.
This study will be conducted in compliance with this protocol, GCP guidelines and all applicable international and local regulatory requirements. The study has approval by the Ethical Review Committee of the Aga Khan University (AKU), the National Bioethics Committee of Pakistan, and ethical approval at WHO/Headquarters in Geneva. All study procedures will be conducted in AKU's field research sites from where subjects will be recruited. The Clinical Trials Unit (CTU) of AKU will be engaged in providing support for specific study procedures conducted at CTU such as randomization, management of vaccines (storage, dispensing and incineration), and other responsibilities agreed in writing.
Adverse events following vaccine administration will be monitored and all serius adverse events will be reported within 24 hours to WHO, DSMB and AKU IRB. All the vaccines used are licensed in Pakistan and in routine use.
详细描述
Background In April 2016, there was globally synchronized switch from tOPV to bivalent OPV (bOPV). The Strategic Advisory Group of Experts on immunization (SAGE) from WHO endorsed the use of IPV in routine immunization globally.(1, 2) However, the IPV introduction pose challenges. The biggest challenge is sustain delivery and availability of IPV not only to the countries with endemic and periodic epidemic for polio disease but also for the countries at risk. Previous research demonstrate that fractional dose of IPV (fIPV) is as efficacious as IPV in children received OPV in their routine immunization.(3, 4) Many countries are in the process of introducing two doses of fIPV in their routine immunization. Pakistan is still one of the two remaining polio endemic countries. There has been gradual decline of wild polio virus 1 cases in 2016 (2014, 306 cases; 2015, 54 cases and 2016, 15 cases as of October 15). This decline is mainly because of strengthening routine immunization, introduction of bOPV and IPV in national polio campaigns. The data on PV2 seroconversion after the introduction of one or two doses of fIPV post bOPV introduction is lacking. There is no data on how long the PV2 serum immunity last. The current study focuses to assess seroconversion for PV2 induced by one and two dose schedule with IPV and compare to fIPV. The investigators also aim to assess the decline in titer within 12 months following second IPV dose and compare the decline between IPV and fIPV schedules.
Study Objectives
- To compare the immunogenicity and seroconversion of PV2 induced by of two doses IPV versus two doses of fractional IPV administered at 14 weeks and 9 months of age.
- To compare the immunogenicity of single dose IPV versus single dose fractional IPV administered at 14 weeks of age.
- To assess the decline in titer within 12 months following IPV compare the decline between IPV and fIPV schedule Methodology Description of the study setting and population Karachi is a large city with five districts and eighteen towns. This study will be conducted in four low-income areas in and around Karachi (4 peri-urban, contiguous coastal villages outside Karachi) located about half hour driving distance from AKU where the Aga Khan University's Department of Paediatrics and Child Health has well-established demographic surveillance, which captures all pregnancies and new births in the area.
Study design This will be a community based randomized control trial. Sample size Assuming 90% of immune response at 21 months of age after administration of two full doses of IPV, 80% power to detect the difference of 15% between arms, 5% level of significance and 10% of drop outs, the required minimum sample size will be 500 (125 in each arm).
Recruitment of the participants, study procedures and administration of informed consent
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
- None
入排标准
- 年龄范围
- 14 Weeks 至 10 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Children aged 14 weeks for arms A and B and 9 months for arms C and D living in four peri-urban slums of Bin Qasim Town, Karachi (Rehri Goth, Bhains Colony, Ali Akber Shah, Ibrahim Hydri) who have not received IPV vaccine during routine immunization for arms A and B and who have documentary evidence of receiving IPV vaccine at 14 weeks of age for arms C and D.
排除标准
- •Child found acutely ill at the time of enrolment and requiring emergent medical care/hospitalization
- •Parents planning to shift out of the four communities during the study time (at least 18 months for arms A and B, and 1 year for arms C and D)
- •Refusal of blood testing
- •Already enrolled in any other clinical trial
研究组 & 干预措施
Arm B
fractional dose inactivated poliovirus vaccine
干预措施: Inactivated Poliovirus vaccine (Biological)
Arm C
inactivated poliovirus vaccine
干预措施: Inactivated Poliovirus vaccine (Biological)
Arm A
Inactivated Poliovirus vaccine
干预措施: Inactivated Poliovirus vaccine (Biological)
Arm D
fractional dose inactivated poliovirus vaccine
干预措施: Inactivated Poliovirus vaccine (Biological)
结局指标
主要结局
sero-conversion defined as the change from seronegative to seropositive (from reciprocal titer of <8 to >8)
时间窗: 14 weeks to 10 months of age and 9 months to 10 months
The difference in seroconversion at 10 months of age between two full dose IPV versus two fractional dose IPV administered at 14 weeks and 9 months of age.
次要结局
- Immune response defined as the combination of both seroconversion and boosting (defined as >4-fold increase in titers)(14 weeks to 18 weeks, 9 months, 10 months and 21 months)
研究者
Ali Faisal Saleem
Assistant Professor
Aga Khan University