Clinical trial NCT03969641: Safety of RIV4 Versus IIV4 in Pregnant Women
Official title: A Prospective, Randomized, Clinical Trial to Compare Adverse Birth Outcomes in Pregnant Women Receiving Quadrivalent Recombinant Influenza Vaccine (RIV4) Versus Quadrivalent Inactivated Influenza Vaccine (IIV4)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Safety
Adverse Event Following Immunisation
Birth Outcomes
Keywords: Vaccination
Safety
Birth outcomes
Flublok
Pregnant
Influenza
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Children's Hospital Medical Center, Cincinnati
name: Boston Medical Center
name: Centers for Disease Control and Prevention
First posted: 2019-05-31
Enrollment: 384
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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

Primary outcomes:
measure: Number of Pregnant Women Vaccinated With RIV4 Versus IIV4 With Adverse Birth Outcomes
timeFrame: Birth outcomes were monitored within postnatal day 28.
Secondary outcomes:
measure: Number of Pregnant Women With Preterm Birth After RIV4 Versus IIV4 Vaccination
timeFrame: Birth outcomes were monitored through 36 weeks 6 days gestation.
measure: Number of Pregnant Women With Fetal or Neonatal Death After RIV4 Versus IIV4 Vaccination
timeFrame: Birth outcomes were monitored through postnatal day 28.
measure: Number of Pregnant Women With Spontaneous Abortion After RIV4 Versus IIV4 Vaccination
timeFrame: Birth outcomes were monitored through 19 weeks 6 days gestation.
measure: Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4
timeFrame: Reactogenicity was measured for 8 days post-vaccination.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Duke University
name: Geeta K Swamy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centers for Disease Control and Prevention
name: Karen R Broder, MD
role: PRINCIPAL_INVESTIGATOR
References: