A Prospective, Randomized, Open-label Clinical Trial to Assess the Safety and Immunogenicity of Simultaneous vs Sequential Administration of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine and Inactivated Influenza Vaccine in Pregnant Women - Pilot
Overview
- Phase
- Phase 4
- Intervention
- Tetanus, Diphtheria, and Pertussis Vaccine
- Conditions
- Pregnancy
- Sponsor
- Duke University
- Enrollment
- 81
- Locations
- 3
- Primary Endpoint
- Percentage of Subjects Recruited Enrollment Period
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
This is a pilot, prospective, randomized, open-label clinical trial. During the study, pregnant women will be randomized (1:1) to receive co-administration of a single intramuscular (IM) 0.5 mL dose of US-licensed inactivated influenza vaccine (IIV) and a single intramuscular (IM) 0.5 mL dose of US-licensed Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) or sequential administration of the vaccines (IIV followed by Tdap ~ 21 days later). Vaccines will be administered by licensed study personnel.
Prior Tdap/Td/TT and influenza vaccine history will be verified by medical record review when possible.
Injection-site (local) and systemic reaction data will be assessed on vaccination day and during the 7 days following vaccination using either identical web-based or paper diaries, depending on study participant preference.
Maternal serum samples will be collected for antibody titers relevant to the Tdap and Influenza at time points that include: prior to vaccination(s), ~21 days post vaccination(s), and at delivery. Additionally, cord blood serum will be analyzed for the same antibody titers.
Pregnant women will be followed with comprehensive obstetric and neonatal outcomes obtained from medical record review.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pregnant, as determined by medical history; 18 - 45 years of age inclusive
- •Intention of receiving Tdap and IIV vaccines based on Advisory Committee on Immunization Practices (ACIP) recommendations
- •Willing to provide written informed consent prior to initiation of any study procedures
- •Singleton gestation ≥ 26 weeks 0 days gestation - ≤32 weeks 0 days gestation at the time of Visit 1 vaccination based on reconciliation of last menstrual period and ultrasound dating. Estimated due date (EDD) and Gestational Age (GA) - EDD will be based on reconciliation of a "sure" first day of the last menstrual period (LMP) and earliest dating ultrasound. If the LMP is uncertain, then the earliest dating ultrasound will be used to determine EDD and GA. If the ultrasound derived-EDD is in agreement with sure-LMP derived EDD, then the LMP-derived EDD is used to determine GA. If the ultrasound derived EDD is not in agreement with the LMP-derived EDD, the ultrasound-derived EDD is used to determine GA.
- •English or Spanish literate
- •Intention of being available for entire study period and complete all relevant study procedures, including follow-up phone calls and collection of delivery information.
Exclusion Criteria
- •For subjects enrolling during the 2016-2017 influenza season: IIV/LAIV receipt during 2016-2017 influenza season prior to study enrollment
- •For subjects enrolling during the 2017-2018 influenza season: IIV/LAIV receipt during 2017-2018 influenza season prior to study enrollment
- •Tdap/Td/TT receipt during current pregnancy prior to study enrollment
- •Has immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months.
- •Has an active neoplastic disease (excluding non-melanoma skin cancer), a history of any hematologic malignancy, current bleeding disorder, or taking anticoagulants (daily low dose aspirin may be acceptable).
- •Has a history of receiving immunoglobulin or other blood product (with exception of Rhogam) within the 3 months prior to enrollment in this study.
- •Known to have pre-existing diabetes mellitus or an autoimmune disorder.
- •Febrile illness within the last 24 hours or an oral temperature \>/= 100.4°F (\>/= 38.0°C) prior to IIV or Tdap administration
- •Contraindication to IIV receipt including history of severe allergic reaction after a previous dose of any influenza vaccine; or to a vaccine component, including egg protein
- •Contraindication to Tdap receipt including history of severe allergic reaction after a previous dose of any tetanus toxoid-, diphtheria toxoid-, or pertussis antigen-containing vaccine or encephalopathy within 7 days of administration of a previous dose of a pertussis antigen-containing vaccine that is not attributable to another identifiable cause
Arms & Interventions
Simultaneous vaccination arm
In the study arm,subjects will receive both Tdap and IIV vaccines during study visit 1.
Intervention: Tetanus, Diphtheria, and Pertussis Vaccine
Simultaneous vaccination arm
In the study arm,subjects will receive both Tdap and IIV vaccines during study visit 1.
Intervention: 2016-2017 Quadrivalent Inactivated Influenza Vaccine
Simultaneous vaccination arm
In the study arm,subjects will receive both Tdap and IIV vaccines during study visit 1.
Intervention: 2017-2018 Quadrivalent Inactivated Influenza Vaccine
Sequential vaccination arm
In this study arm, subjects will receive the IIV vaccine during study visit 1. Approximately 3 weeks later, they will receive the Tdap vaccine during study visit 4.
Intervention: Tetanus, Diphtheria, and Pertussis Vaccine
Sequential vaccination arm
In this study arm, subjects will receive the IIV vaccine during study visit 1. Approximately 3 weeks later, they will receive the Tdap vaccine during study visit 4.
Intervention: 2016-2017 Quadrivalent Inactivated Influenza Vaccine
Sequential vaccination arm
In this study arm, subjects will receive the IIV vaccine during study visit 1. Approximately 3 weeks later, they will receive the Tdap vaccine during study visit 4.
Intervention: 2017-2018 Quadrivalent Inactivated Influenza Vaccine
Outcomes
Primary Outcomes
Percentage of Subjects Recruited Enrollment Period
Time Frame: Approximately 1 year
Percentage of subjects recruited during 4 month enrollment period
Feasibility Reported as Percentage of Timely Collected Biospecimens
Time Frame: Approximately 1 year
Timeliness is defined as collected within the visit window
Percentage of Participants With Injection-site Reactions Post Tdap and IIV4 Administration
Time Frame: 8 days post vaccine administration
Percentage of injection-site reactions will be compared in simultaneous and sequential groups as determined by self-assessment via memory aid
Percentage of Participants With Systemic Reactions Post Tdap and IIV4 Administration - Visit 4
Time Frame: 8 days post vaccine administration
Percentage of systemic reactions will be compared in simultaneous and sequential groups as determined by self-assessment via memory aid
Pertussis Serum Antibody Levels, as Measured by Geometric Mean Titers
Time Frame: Pre-vaccination and approximately 21 days post vaccination and at Delivery
Measurement of serum antibody levels to pertussis antigens, in maternal blood pre- and post-vaccination, maternal blood at delivery and infant cord blood obtained at delivery
Percentage of Participants With Systemic Reactions Post Tdap and IIV4 Administration - Visit 1
Time Frame: 8 days post vaccine administration
Percentage of systemic reactions will be compared in simultaneous and sequential groups as determined by self-assessment via memory aid
Feasibility as Measured by Participant Retention (Percentage of Participants Who Complete All Visits)
Time Frame: Approximately 1 year
Percentage of participants that completed all in-person and delivery visits
Feasibility Reported as Percentage of Reactogenicity Data Collected
Time Frame: Approximately 1 year
Percentage of reactogenicity data days reported (days reported / total possible days)
Feasibility Reported as Percentage of Adequate Biospecimens Collected
Time Frame: Approximately 1 year
Percentage of samples collected (sample timepoints collected / total possible sample timepoints)
Percentage of Subjects With Seroprotection as Determined by Diphtheria Serum Antibody Levels (Defined as ≥ 0.1 IU/mL)
Time Frame: Pre vaccination and approximately 21 days post vaccination and at Delivery
Measurement of serum antibody levels to diphtheria toxoids, in maternal blood pre- and post-vaccination, maternal blood at delivery and infant cord blood obtained at delivery
Percentage of Subjects With Seroprotection as Determined by Tetanus Serum Antibody Levels (Defined as ≥ 0.1 IU/mL)
Time Frame: 21 days post vaccination
Measurement of serum antibody levels to tetanus toxoids, in maternal blood pre- and post-vaccination, maternal blood at delivery and infant cord blood obtained at delivery
Percentage of Subjects With Seroprotection as Determined by Influenza Serum Antibody Levels (≥1:40) (Pre- and Post-immunization) and Seroconversion (4-fold Rise From Baseline or a Change From <1:10 to ≥1:40) )
Time Frame: Pre and 21 days post vaccination and at Delivery
Measurement of serum antibody levels to influenza antigens in maternal blood and infant cord blood obtained at delivery
Secondary Outcomes
- Feasibility as Measured by Percentage of Blood Samples in Testable Condition(Approximately 1 year)
- Feasibility as Measured by Percentage of Blood Samples in With Sufficient Volume for Testing(Approximately 1 year)
- Feasibility as Measured by Percentage of Testable Blood Samples Completed(Approximately 1 year)
- Number of Participants With Adverse Infant Outcomes Based on Medical Record Review(approximately 2 months)
- Percentage of Participants With Clinical Chorioamnionitis(at the time of delivery)
- Percentage of Participants With Histologic Chorioamnionitis on Surgical Pathology Examination of Placental Tissue(after delivery, approximately up to 2 weeks)
- Number of Participants With Adverse Maternal Outcomes(Up to the 6-week postpartum visit)