Safety of RIV4 Versus IIV4 in Pregnant Women
Condition: Safety; Adverse Event Following Immunisation; Birth Outcomes
Intervention: Quadrivalent Recombinant Influenza Vaccine; Quadrivalent Inactivated Influenza Vaccine
Intervention description: The first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology; Standard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs.
Intervention MeSH terms: Vaccines
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 384.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Vaccination; Safety; Birth outcomes; Flublok; Pregnant; Influenza

Summary:

      This is a prospective, randomized clinical trial. During the study, pregnant women will be
      randomized (1:1) to receive RIV4 or IIV4. Vaccines will be administered by licensed
      providers.

      Prior 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 8 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 Influenza at time
      points that include: prior to vaccination and ~29 days post vaccination. When feasible,
      maternal blood at delivery and cord blood serum will be analyzed for the same antibody
      titers.

      Pregnant women will be followed through delivery with comprehensive obstetric and neonatal
      outcomes obtained from medical record review for 90 days of life.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pregnant, as determined by medical history

          2. Age ≥ 18 years of age at enrollment

          3. Intention of receiving influenza vaccine based on ACIP-CDC guidelines

          4. Willing to provide written informed consent prior to initiation of any study
             procedures

          5. Gestational age at vaccination ≤ 34 weeks 0 days 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 "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.

          6. English or Spanish literate

          7. 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. Influenza vaccine receipt during 2019-2020 or 2020-2021 influenza season prior to
             study enrollment.

          2. Participation in this study in 2019-2020 influenza season

          3. Any condition that may interfere with assessment of local injection site reactions,
             e.g. obscuring tattoos

          4. Known or suspected immunosuppression as a result of an underlying illness or treatment

          5. Use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months

          6. Use of oral or parenteral corticosteroids (≥ 20mg/day prednisone equivalent) or
             high-dose inhaled glucocorticoid for ≥ 14 consecutive days within the preceding 30
             days

          7. Has an active neoplastic disease (excluding non-melanoma skin cancer), a history of
             any hematologic malignancy, current bleeding disorder, or taking anticoagulants (a
             daily aspirin is acceptable)

          8. Has a history of receiving immunoglobulin or other blood product (with exception of Rh
             immunoglobulin) within the 3 months prior to study vaccination.

          9. History of febrile illness (> 100.4°F or 38°C) within the past 24 hours prior to study
             vaccination

         10. Contraindication to IIV or RIV receipt including history of severe allergic reaction
             after a previous dose of any influenza vaccine; or to a vaccine component, including
             egg protein

         11. History of Guillain-Barré syndrome within 6 weeks of a prior dose of any influenza
             vaccine

         12. Receipt of any licensed vaccine within 7 days prior to study vaccination or intention
             of receiving any vaccines during 8-day post-vaccination period

         13. Receipt of live vaccine during current pregnancy

         14. Signs or symptoms of active preterm labor, defined as regular uterine contractions
             with cervical change (dilation/effacement)

         15. Known multi-fetal gestation or fetal congenital anomaly, e.g. genetic abnormality or
             major congenital malformation based on antenatal ultrasound

         16. Anyone who is already enrolled or plans to enroll in another randomized clinical trial
             with any drug, vaccine or medical device. Co-enrollment in observational or behavioral
             intervention studies are allowed at any time

         17. Any condition which, in the opinion of the investigators, may pose a health risk to
             the participant or interfere with the evaluation of the study objectives.

         18. Anyone who is a relative of any research study personnel or is an employee supervised
             by study staff