SafetyPhase 4NCT03969641
Safety of RIV4 Versus IIV4 in Pregnant Women
A Phase 4 study testing Quadrivalent Recombinant Influenza Vaccine and Quadrivalent Inactivated Influenza Vaccine in people with Safety and Adverse Event Following Immunisation, run by Duke University at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Safety, Adverse Event Following Immunisation, Birth Outcomes
- What is being tested?
- Quadrivalent Recombinant Influenza Vaccine and Quadrivalent Inactivated Influenza Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 384 participants
- Where
- 3 sitesUnited States
- Study dates
- 5 Sep 2019to 29 Sep 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Pregnant, as determined by medical history
- Age ≥ 18 years of age at enrollment
- Intention of receiving influenza vaccine based on ACIP-CDC guidelines
- Willing to provide written informed consent prior to initiation of any study procedures
- 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.
- English or Spanish literate
- Intention of being available for entire study period and complete all relevant study procedures, including follow-up phone calls and collection of delivery information.
Who cannot join
- Influenza vaccine receipt during 2019-2020 or 2020-2021 influenza season prior to study enrollment.
- Participation in this study in 2019-2020 influenza season
- Any condition that may interfere with assessment of local injection site reactions, e.g. obscuring tattoos
- Known or suspected immunosuppression as a result of an underlying illness or treatment
- Use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months
- Use of oral or parenteral corticosteroids (≥ 20mg/day prednisone equivalent) or high-dose inhaled glucocorticoid for ≥ 14 consecutive days within the preceding 30 days
Show all 18Show fewer
- 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)
- Has a history of receiving immunoglobulin or other blood product (with exception of Rh immunoglobulin) within the 3 months prior to study vaccination.
- History of febrile illness (> 100.4°F or 38°C) within the past 24 hours prior to study vaccination
- 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
- History of Guillain-Barré syndrome within 6 weeks of a prior dose of any influenza vaccine
- Receipt of any licensed vaccine within 7 days prior to study vaccination or intention of receiving any vaccines during 8-day post-vaccination period
- Receipt of live vaccine during current pregnancy
- Signs or symptoms of active preterm labor, defined as regular uterine contractions with cervical change (dilation/effacement)
- Known multi-fetal gestation or fetal congenital anomaly, e.g. genetic abnormality or major congenital malformation based on antenatal ultrasound
- 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
- 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.
- Anyone who is a relative of any research study personnel or is an employee supervised by study staff
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Boston Medical Center
Boston, Massachusetts, 02118
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Duke University Medical Center
Durham, North Carolina, 27705
About this study
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)
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.
Read more
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.
- Conditions
- Safety, Adverse Event Following Immunisation, Birth Outcomes
- Being tested
- Quadrivalent Recombinant Influenza Vaccine, Quadrivalent Inactivated Influenza Vaccine
- Keywords
- Vaccination, Safety, Birth outcomes, Flublok, Pregnant, Influenza
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quadrivalent Recombinant Influenza VaccineBiological
Also called Flublok Quadrivalent
The first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology
Quadrivalent Inactivated Influenza VaccineBiological
Also called Flulaval
Standard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs.
| Study group | Role | What they receive |
|---|---|---|
| RIV4 | Experimental | The first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology Receives: Biological: Quadrivalent Recombinant Influenza Vaccine |
| IIV4 | Active comparator | Standard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs. Receives: Biological: Quadrivalent Inactivated Influenza Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Birth outcomes were monitored within postnatal day 28.
Secondary outcomes (4)
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.
Measured: Birth outcomes were monitored through 36 weeks 6 days gestation.
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.
Measured: Birth outcomes were monitored through postnatal day 28.
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.
Measured: Birth outcomes were monitored through 19 weeks 6 days gestation.
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.
Measured: Reactogenicity was measured for 8 days post-vaccination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2019
- Study start5 Sep 2019
- Primary completion29 Sep 2021
- Study completion29 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SafetyStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 384 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati, Boston Medical Center, Centers for Disease Control and Prevention
- Responsible party
- Sponsor
- Investigators
- Geeta K Swamy, MD, Principal investigator, Duke UniversityKaren R Broder, MD, Principal investigator, Centers for Disease Control and Prevention
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03969641
- Sponsor's protocol ID
- Pro00101707
- Status last verified
- Jan 2023
- First submitted
- 28 May 2019
- Last updated
- 11 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03969641
- Acronym / sponsor ID
- Pro00101707
- Conditions
- Safety, Adverse Event Following Immunisation, Birth Outcomes
- Keywords
- Vaccination, Safety, Birth outcomes, Flublok, Pregnant, Influenza
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 384 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati, Boston Medical Center, Centers for Disease Control and Prevention
- Study start
- 5 Sep 2019 (actual)
- Primary completion
- 29 Sep 2021 (actual)
- Study completion
- 29 Sep 2021 (actual)
- First posted
- 31 May 2019 (actual)
- Results
- Posted 27 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RIV4 | Experimental | Biological: Quadrivalent Recombinant Influenza VaccineThe first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology |
| IIV4 | Active comparator | Biological: Quadrivalent Inactivated Influenza VaccineStandard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Pregnant, as determined by medical history
- Age ≥ 18 years of age at enrollment
- Intention of receiving influenza vaccine based on ACIP-CDC guidelines
- Willing to provide written informed consent prior to initiation of any study procedures
- 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.
Key exclusion criteria (18 listed)
- Influenza vaccine receipt during 2019-2020 or 2020-2021 influenza season prior to study enrollment.
- Participation in this study in 2019-2020 influenza season
- Any condition that may interfere with assessment of local injection site reactions, e.g. obscuring tattoos
- Known or suspected immunosuppression as a result of an underlying illness or treatment
- Use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Quadrivalent Recombinant Influenza VaccineAlso: Flublok QuadrivalentThe first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology | Biological | RIV4 |
| Quadrivalent Inactivated Influenza VaccineAlso: FlulavalStandard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs. | Biological | IIV4 |
Primary outcome
Number of Pregnant Women Vaccinated With RIV4 Versus IIV4 With Adverse Birth Outcomes
Time frame: Birth outcomes were monitored within postnatal day 28.
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
4 secondary outcomes
Number of Pregnant Women With Preterm Birth After RIV4 Versus IIV4 Vaccination
Time frame: Birth outcomes were monitored through 36 weeks 6 days gestation.
Number of Pregnant Women With Fetal or Neonatal Death After RIV4 Versus IIV4 Vaccination
Time frame: Birth outcomes were monitored through postnatal day 28.
Number of Pregnant Women With Spontaneous Abortion After RIV4 Versus IIV4 Vaccination
Time frame: Birth outcomes were monitored through 19 weeks 6 days gestation.
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4
Time frame: Reactogenicity was measured for 8 days post-vaccination.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geeta K Swamy, MD principal investigator
Duke University
Karen R Broder, MD principal investigator
Centers for Disease Control and Prevention
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Quadrivalent Recombinant Influenza Vaccine and Quadrivalent Inactivated Influenza Vaccine in people with Safety and Adverse Event Following Immunisation, run by Duke University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Pregnant Women Vaccinated With RIV4 Versus IIV4 With Adverse Birth Outcomes (time frame: Birth outcomes were monitored within postnatal day 28.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2023.