Clinical trial NCT02783170: Safety and Immunogenicity of Simultaneous Tdap and IIV in Pregnant Women
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pregnancy
Keywords: Tdap vaccine
Flu vaccine
vaccines in pregnancy
immunizations in pregnancy
Whooping Cough
Pertussis
Influenza
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Children's Hospital Medical Center, Cincinnati
name: Centers for Disease Control and Prevention
First posted: 2016-05-26
Enrollment: 81
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Percentage of Participants With Injection-site Reactions Post Tdap and IIV4 Administration
timeFrame: 8 days post vaccine administration
measure: Percentage of Participants With Systemic Reactions Post Tdap and IIV4 Administration - Visit 1
timeFrame: 8 days post vaccine administration
measure: Percentage of Participants With Systemic Reactions Post Tdap and IIV4 Administration - Visit 4
timeFrame: 8 days post vaccine administration
measure: Pertussis Serum Antibody Levels, as Measured by Geometric Mean Titers
timeFrame: Pre-vaccination and approximately 21 days post vaccination and at Delivery
measure: Percentage of Subjects With Seroprotection as Determined by Diphtheria Serum Antibody Levels (Defined as ≥ 0.1 IU/mL)
timeFrame: Pre vaccination and approximately 21 days post vaccination and at Delivery
measure: Percentage of Subjects With Seroprotection as Determined by Tetanus Serum Antibody Levels (Defined as ≥ 0.1 IU/mL)
timeFrame: 21 days post vaccination
measure: 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) )
timeFrame: Pre and 21 days post vaccination and at Delivery
measure: Percentage of Subjects Recruited Enrollment Period
timeFrame: Approximately 1 year
measure: Feasibility as Measured by Participant Retention (Percentage of Participants Who Complete All Visits)
timeFrame: Approximately 1 year
measure: Feasibility Reported as Percentage of Reactogenicity Data Collected
timeFrame: Approximately 1 year
measure: Feasibility Reported as Percentage of Adequate Biospecimens Collected
timeFrame: Approximately 1 year
measure: Feasibility Reported as Percentage of Timely Collected Biospecimens
timeFrame: Approximately 1 year
Secondary outcomes:
measure: Number of Participants With Adverse Maternal Outcomes
timeFrame: Up to the 6-week postpartum visit
measure: Number of Participants With Adverse Infant Outcomes Based on Medical Record Review
timeFrame: approximately 2 months
measure: Percentage of Participants With Clinical Chorioamnionitis
timeFrame: at the time of delivery
measure: Percentage of Participants With Histologic Chorioamnionitis on Surgical Pathology Examination of Placental Tissue
timeFrame: after delivery, approximately up to 2 weeks
measure: Feasibility as Measured by Percentage of Blood Samples in Testable Condition
timeFrame: Approximately 1 year
measure: Feasibility as Measured by Percentage of Blood Samples in With Sufficient Volume for Testing
timeFrame: Approximately 1 year
measure: Feasibility as Measured by Percentage of Testable Blood Samples Completed
timeFrame: Approximately 1 year
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Centers for Disease Control and Prevention
state: Georgia
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Duke University
name: Geeta Swamy, MD
role: PRINCIPAL_INVESTIGATOR
References: