Safety of RIV4 Versus IIV4 in Pregnant Women

Safety Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03969641
• Other study ID #: Pro00101707
• Status: Completed
• Phase: Phase 4
• Start date: September 5, 2019
• Est. completion date: September 29, 2021

Study information

• Verified date: January 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 384
• Est. completion date: September 29, 2021
• Est. primary completion date: September 29, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adverse Event Following Immunisation
• Birth Outcomes
• Safety

Intervention

Biological:
• Quadrivalent Recombinant Influenza Vaccine
The first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology
• Quadrivalent Inactivated Influenza Vaccine
Standard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs.

Locations

Country	Name	City	State
United States	Boston Medical Center	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Duke University	Boston Medical Center, Centers for Disease Control and Prevention, Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Pregnant Women Vaccinated With RIV4 Versus IIV4 With Adverse Birth Outcomes	As measured by the number of women experiencing one of the following: Adverse birth outcome is a composite of occurrence of at least one of the following: preterm birth, spontaneous abortion, fetal death, or neonatal death.; Preterm birth- born alive at less than 37 weeks and 0 days gestation; Spontaneous abortion (SAB)- pregnancy loss prior to 20 weeks 0 days; Fetal death- intrauterine death of fetus at or after 20 weeks 0 days; Neonatal death- infant death within first 28 days of life	Birth outcomes were monitored within postnatal day 28.
Secondary	Number of Pregnant Women With Preterm Birth After RIV4 Versus IIV4 Vaccination	Preterm birth is defined as born alive at less than 37 weeks and 0 days gestation.	Birth outcomes were monitored through 36 weeks 6 days gestation.
Secondary	Number of Pregnant Women With Fetal or Neonatal Death After RIV4 Versus IIV4 Vaccination	Fetal death is defined as intrauterine death of fetus at or after 20 weeks 0 days. Neonatal death is defined as infant death within first 28 days of life.	Birth outcomes were monitored through postnatal day 28.
Secondary	Number of Pregnant Women With Spontaneous Abortion After RIV4 Versus IIV4 Vaccination	Spontaneous abortion (SAB) is defined as pregnancy loss prior to 20 weeks 0 days.	Birth outcomes were monitored through 19 weeks 6 days gestation.
Secondary	Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4	Reactogenicity events include Injection Site Pain, Injection Site Redness, Injection Site Tenderness, Injection Site Swelling, Nausea, Vomiting, Diarrhea, Abdominal Pain, Headache, Chills/Shivering, Body Rash, Fever, Malaise (Fatigue), Myalgia (Body Aches), and Joint Pain.	Reactogenicity was measured for 8 days post-vaccination.