Safety and Immunogenicity of Simultaneous Tdap and IIV in Pregnant Women
Condition: Pregnancy
Intervention: Tetanus, Diphtheria, and Pertussis Vaccine; 2016-2017 Quadrivalent Inactivated Influenza Vaccine; 2017-2018 Quadrivalent Inactivated Influenza Vaccine
Intervention MeSH terms: Vaccines
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 81.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Tdap vaccine; Flu vaccine; vaccines in pregnancy; immunizations in pregnancy; Whooping Cough; Pertussis; Influenza

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pregnant, as determined by medical history; 18 - 45 years of age inclusive

          2. Intention of receiving Tdap and IIV vaccines based on Advisory Committee on
             Immunization Practices (ACIP) recommendations

          3. Willing to provide written informed consent prior to initiation of any study
             procedures

          4. 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.

          5. English or Spanish literate

          6. 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:

          1. For subjects enrolling during the 2016-2017 influenza season: IIV/LAIV receipt during
             2016-2017 influenza season prior to study enrollment

          2. For subjects enrolling during the 2017-2018 influenza season: IIV/LAIV receipt during
             2017-2018 influenza season prior to study enrollment

             2. Tdap/Td/TT receipt during current pregnancy prior to study enrollment 3. 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.

             4. 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).

             5. Has a history of receiving immunoglobulin or other blood product (with exception of
             Rhogam) within the 3 months prior to enrollment in this study.

             6. Known to have pre-existing diabetes mellitus or an autoimmune disorder. 7. Febrile
             illness within the last 24 hours or an oral temperature >/= 100.4°F (>/= 38.0°C) prior
             to IIV or Tdap administration 8. 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 9. 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 10. Arthus-type
             hypersensitivity reaction following a prior dose of a tetanus toxoid-containing
             vaccine within the last 10 years 11. Any condition that may interfere with assessment
             of local injection site reactions, e.g. lymphadenectomy or obscuring tattoos 12.
             History of Guillain-Barré syndrome within 6 weeks of a prior dose of any tetanus
             toxoid-, diphtheria toxoid- or pertussis antigen-containing vaccine or influenza
             vaccine 13. Known or suspected impairment of immunologic function including infection
             with HIV, hepatitis B or C 14. Use of immunosuppressive or cytotoxic drugs except
             receipt of oral or parenteral (intravenous, subcutaneous or intramuscular)
             corticosteroids 30 or more days prior to enrollment. Persons who have used oral or
             parenteral corticosteroids within 12 months prior to enrollment may be enrolled if the
             longest course of therapy was less than 14 consecutive days and no dose was given
             within 30 days of enrollment. Intraarticular, bursal, tendon, or epidural injections
             of corticosteroids are permissible if the most recent injection was 30 or more days
             prior to enrolment. Persons applying topically corticosteroid in either upper arm
             (i.e. injection site) may be enrolled 1 or more days after their therapy is completed.
             Corticosteroids administered topically at non-injection sites, by inhalation or
             intranasally are permissible 15. Receipt of any licensed vaccine within 14 days prior
             to study vaccination or planning receipt of any vaccines (except study vaccines) prior
             to Visit 7 follow up.

             16. Receipt of live vaccine during current pregnancy. 17. High risk for preterm birth
             (active preterm labor, short cervix, cervical cerclage, receipt of antenatal
             corticosteroids for fetal lung maturity prior to Visit 1) 18. Antenatal ultrasound
             diagnosis of fetal growth restriction, defined as < 10th percentile estimated fetal
             weight for gestational age 19. Known fetal congenital anomaly, e.g. genetic
             abnormality or malformation based on antenatal ultrasound 20. Any condition which, in
             the opinion of the investigators, may pose a health risk to the subject or interfere
             with the evaluation of the study objectives.

             21. Anyone who is a relative of any research study personnel 22. Anyone who is an
             employee of any research study personnel 23. Anyone who is already enrolled or plans
             to enroll in another clinical trial with an investigational product. Co-enrollment in
             observational or behavioral intervention studies are allowed at any time.

             24. Previous participation in the study.