Concurrent Versus Sequential Administration of Tdap and RSV Vaccines in Pregnancy - A Pilot Feasibility Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 8
- 主要终点
- Feasibility of conducting a randomized controlled trial - Screening Rate
研究概览
简要总结
The goal of this clinical trial is to learn if the RSV vaccine (protects against respiratory syncytial virus) and Tdap vaccine (protects against pertussis) are most effective in pregnant individuals when taken together at the same visit, or separately at different visits. This clinical trial will also learn about the safety and immune responses of these vaccines in pregnancy.
The Main question:
-Is it possible to run a successful trial that tests how safe and effective it is to give Tdap and RSV vaccines in pregnancy either at the same time or one after the other, at different visits?
The Secondary question:
-To determine how safe and how well the Tdap and RSV vaccines work when given in pregnancy either at the same time or one after the other, at different visits.
The Exploratory (optional participation) questions:
- To measure the levels of antibodies against whooping cough (pertussis) and RSV in mothers at 7 and 19 months after giving birth, depending on whether they got the vaccines at the same time or one after the other during pregnancy.
- To measure whooping cough antibody levels in the babies at 2, 7, and 19 months of age, whose mothers who received the vaccines in pregnancy.
- To measure the levels of RSV antibodies in the mothers' breast milk at 1 week, 2 weeks, 4 weeks, and 2 months after giving birth.
Participants will be randomly assigned to Group 1 (vaccines given at the same time, same visit) or Group 2 (vaccines given one after the other, at different visits).
There are 4 visits as part of the main study, and 6 additional visits as part of the optional study (exploratory questions).
Visit 1-2: Blood collection and vaccines administered Visit 3-4: Blood work (cord blood sample collection from infant, after delivery, if possible) Visit 5-8: Breast milk collection Visit 8-10: Blood collection (infant blood collection only at Visit 8).
Participants will be asked to keep a diary of symptoms throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Data Safety Monitoring Board members, unless unblinding is required to provide a comprehensive safety assessment.
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Healthy pregnant individuals with a singleton pregnancy aged 18-49 years.
- •Gestational age 28-29+6 WG at time of study screening, enrolment and randomization as per documented first trimester (less than or equal to13+6 WG) ultrasound, or the first date of last menstrual period if ultrasound not obtained in the first trimester, or the age of the embryo and the date of transfer if pregnancy resulted from assisted reproductive technology.
- •Able to comply with the study procedures required to achieve primary objective of this pilot trial (not being able to comply with procedures required to achieve exploratory objectives is not an
排除标准
- •Informed consent read, understood and signed prior to study-specific procedures.
- •Exclusion Criteria
- •Any of the following:
- •Receipt of RSV vaccine anytime.
- •Receipt of immunoglobulins (except Rho D) within 1 year prior to vaccination.
- •Documented receipt of pertussis vaccine within 2 years prior to vaccination.
- •Documented pertussis infection (by culture or polymerase chain reaction) within 2 years prior to vaccination.
- •Receipt of blood transfusion products within 6 months prior to vaccination.
- •Primary or secondary immunologic disorder or immunosuppression.
- •Any conditions that, in the investigator's judgement, may interfere with subject's ability to comply with study procedures or receipt of prenatal care, such as behavioural or cognitive impairment or neuropsychiatric illness.
- •Preconception diabetes mellitus (defined as: previous diagnosis of diabetes while not pregnant OR First trimester hemoglobin A1c level of 6.5% [47.5 mmol/mol] OR First trimester fasting blood glucose 126 mg/dL [7 mmol/L]).
- •Preconception chronic hypertension (defined as: sustained elevation in the systolic blood pressure to ≥140 mmHg or the diastolic blood pressure to ≥90 mmHg, that is diagnosed either prior to pregnancy or prior to 20 WG).
- •Congenital anomalies per ultrasound.
- •Hepatitis B infection; Hepatitis C infection; Untreated syphilis.
- •Contraindication to receipt of Tdap (BOOSTRIX, GSK): a) Hypersensitivity to any component of the Tdap (BOOSTRIX, GSK) vaccine or individuals having shown signs of hypersensitivity after previous administration of diphtheria, tetanus, or pertussis vaccines; b) Encephalopathy of unknown etiology, occurring within 7 days following previous vaccination with pertussis containing vaccine; c) Transient thrombocytopenia or neurological complications following an earlier immunization against diphtheria and/or tetanus.
- •Contraindication to receipt of RSVpreF (ABRYSVOTM, Pfizer): Hypersensitivity to the active substance or to any component of the vaccine.
- •Pregnancy complications at the time of recruitment that are risk factors for preterm delivery:
- •Gestational hypertension (defined as new onset hypertension after 20 WG of systolic blood pressure is ≥140 mmHg or the diastolic blood pressure is ≥90 mmHg on two measurements at a minimum of one hour apart);
- •Pre-eclampsia (defined as development of gestational hypertension [as defined in #a above] and proteinuria after 20 WG (Proteinuria defined as ≥300 mg in a 24 h urine specimen, or ≥0.30 on a spot protein: creatinine ratio, or ≥1+ on a dipstick;
- •Gestational diabetes mellitus uncontrolled at time of consent (gestational diabetes is defined as a clinical syndrome characterized by the absence of preconception diabetes mellitus [as defined in #8 above] AND identification of sustained hyperglycemia during pregnancy not due to other known causes (i.e. corticosteroids, beta-mimetics, etc.) based on positive internationally recognized oral glucose tolerance test OR fasting plasma glucose of 92-125 mg/dL [5.1-6.9 mmol/l] using venous or capillary blood samples;
- •Fetal growth restriction (defined as estimated fetal weight below 10% using locally-accepted growth curve AND Absent or reversed end-diastolic flow of the umbilical artery Doppler OR Oligohydramnios [defined as a decreased amniotic fluid volume as defined by amniotic fluid index less than 8 cm or deepest vertical pocket less than 2 cm in the presence of intact membranes without concern for fetal anomalies contributing to its etiology]);
- •Placenta anomalies (placenta previa and abruptio, vasa previa);
- •Polyhydramnios (defined as abnormal increase in the volume of amniotic fluid as either a deepest vertical pocket of ≥8 cm or an amniotic fluid index of ≥24 cm);
- •Oligohydramnios (decreased amniotic fluid volume as defined in d above);
- •Short uterine cervix (<25 mm in the second trimester of pregnancy);
- •A significant acute disease or oral temperature ≥38 Co within 24 hours prior to vaccination. Participants can return for evaluation to be randomized/vaccinated 72 hours after symptoms resolve, if they are still within 28-29+6 WG.
研究组 & 干预措施
Group 1: Concurrent Assignment
干预措施: RSV Vaccine (Biological)
Group 2: Sequential Assignment
干预措施: RSV Vaccine (Biological)
Group 1: Concurrent Assignment
干预措施: Tdap Vaccine Administration (Biological)
Group 1: Concurrent Assignment
干预措施: Saline (as a placebo) (Other)
Group 2: Sequential Assignment
干预措施: Tdap Vaccine Administration (Biological)
Group 2: Sequential Assignment
干预措施: Saline (as a placebo) (Other)
结局指标
主要结局
Feasibility of conducting a randomized controlled trial - Screening Rate
时间窗: From enrollment to the end of visit 4 (end of main study) at around 12 weeks
To evaluate the feasibility of conducting a randomized controlled trial (RCT) that would test the safety and immunogenicity of Tdap and RSV concurrent and sequential administration in pregnancy. Number of participants screened monthly in each site and overall.
Feasibility of conducting a randomized controlled trial - Consent & Randomization Rate
时间窗: From enrollment to the end of visit 4 (end of main study) at around 12 weeks
To evaluate the feasibility of conducting a randomized controlled trial (RCT) that would test the safety and immunogenicity of Tdap and RSV concurrent and sequential administration in pregnancy. Proportion/number of participants who consent and successfully randomized out of screened individuals in each site and overall.
Feasibility of conducting a randomized controlled trial - Retention Rate
时间窗: From enrollment to the end of visit 4 (end of main study) at around 12 weeks
To evaluate the feasibility of conducting a randomized controlled trial (RCT) that would test the safety and immunogenicity of Tdap and RSV concurrent and sequential administration in pregnancy. Proportion of randomized participants who complete the first four study visits in each site and overall.
Feasibility of conducting a randomized controlled trial - Trial Protocol Compliance Rate
时间窗: From enrollment to the end of visit 4 (end of main study) at around 12 weeks
To evaluate the feasibility of conducting a randomized controlled trial (RCT) that would test the safety and immunogenicity of Tdap and RSV concurrent and sequential administration in pregnancy. Percentage of participants who do not deviate from the protocol and complete vaccination and the first four visits in each site and overall.
次要结局
- Safety Outcomes - Rates of Adverse Events Following Immunization in Participants(Up to 14 weeks after first vaccination)
- Safety Outcomes - Rates of Adverse Events of Special Interest in Participants during Pregnancy and Delivery(Up to 14 weeks after first vaccination)
- Safety Outcomes - Rates of Serious Adverse Events in Participants during Pregnancy and Delivery(Up to 14 weeks after first vaccination)
- Immunogenicity - Seroconversion rate of anti-pertussis toxin IgG(4 weeks after vaccination with Tdap)
- Immunogenicity - Seroconversion rate of anti-Filamentous hemagglutinin IgG(4 weeks after vaccination with Tdap)
- Immunogenicity - Seroconversion rate of anti-Pertactin IgG(4 weeks after vaccination with Tdap)
- Immunogenicity - Seroconversion rate of Prefusion RSV F protein IgG(4 weeks after vaccination with RSV vaccine)
- Immunogenicity - Anti-Pertussis toxin IgG levels at term birth (maternal and cord sera)(Up to 14 weeks after vaccination with Tdap)
- Immunogenicity - Anti-Filamentous hemagglutinin IgG levels at term birth (maternal and cord sera)(Up to 14 weeks after vaccination with Tdap)
- Immunogenicity - Anti-Pertactin IgG levels at term birth (maternal and cord sera)(Up to 14 weeks after vaccination with Tdap)
- Immunogenicity - Prefusion RSV F protein IgG levels at term birth (maternal and cord sera)(Up to 14 weeks after vaccination with RSV vaccine)
研究者
Bahaa Abu Raya
Principal Investigator
Canadian Immunization Research Network