Trial Outcomes & Findings for Safety of RIV4 Versus IIV4 in Pregnant Women (NCT NCT03969641)

NCT ID: NCT03969641

Last Updated: 2023-01-11

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 384 participants
• Primary outcome timeframe: Birth outcomes were monitored within postnatal day 28.
• Results posted on: 2023-01-11

Participant Flow

Participant milestones

Measure	IIV4 Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.	RIV4 Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)
Overall Study STARTED	193	191
Overall Study COMPLETED	184	181
Overall Study NOT COMPLETED	9	10

Reasons for withdrawal

Measure	IIV4 Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.	RIV4 Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)
Overall Study Lost to Follow-up	5	3
Overall Study Withdrawal by Subject	1	2
Overall Study Found to be ineligible	1	1
Overall Study Intrauterine fetal demise (IUFD)	0	2
Overall Study Spontaneous abortion (SAB)	2	1
Overall Study Elective termination	0	1

Baseline Characteristics

Safety of RIV4 Versus IIV4 in Pregnant Women

Baseline characteristics by cohort

Measure	RIV4 n=190 Participants Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)	IIV4 n=192 Participants Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.	Total n=382 Participants Total of all reporting groups
Age, Customized Maternal Age	31 years n=5 Participants	31 years n=7 Participants	31 years n=5 Participants
Sex: Female, Male Female	190 Participants n=5 Participants	192 Participants n=7 Participants	382 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	166 Participants n=5 Participants	163 Participants n=7 Participants	329 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	63 Participants n=5 Participants	63 Participants n=7 Participants	126 Participants n=5 Participants
Race (NIH/OMB) White	98 Participants n=5 Participants	114 Participants n=7 Participants	212 Participants n=5 Participants
Race (NIH/OMB) More than one race	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	190 Participants n=5 Participants	192 Participants n=7 Participants	382 Participants n=5 Participants
Gestational Age at Enrollment less than 20 weeks	65 Participants n=5 Participants	78 Participants n=7 Participants	143 Participants n=5 Participants
Gestational Age at Enrollment 20-34 weeks	125 Participants n=5 Participants	114 Participants n=7 Participants	239 Participants n=5 Participants
Receipt of prior influenza season vaccine	143 Participants n=5 Participants	138 Participants n=7 Participants	281 Participants n=5 Participants

PRIMARY outcome

Timeframe: Birth outcomes were monitored within postnatal day 28.

Population: mITT Population- any participant that was enrolled, randomized into the study, and received study vaccine

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

Outcome measures

Measure	RIV4 n=190 Participants Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)	IIV4 n=192 Participants Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.
Number of Pregnant Women Vaccinated With RIV4 Versus IIV4 With Adverse Birth Outcomes	17 Participants	21 Participants

SECONDARY outcome

Timeframe: Birth outcomes were monitored through 36 weeks 6 days gestation.

Population: mITT Population- any participant that was enrolled, randomized into the study, and received study vaccine

Preterm birth is defined as born alive at less than 37 weeks and 0 days gestation.

Outcome measures

Measure	RIV4 n=190 Participants Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)	IIV4 n=192 Participants Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.
Number of Pregnant Women With Preterm Birth After RIV4 Versus IIV4 Vaccination	14 Participants	19 Participants

SECONDARY outcome

Timeframe: Birth outcomes were monitored through postnatal day 28.

Population: mITT Population- any participant that was enrolled, randomized into the study, and received study vaccine

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.

Outcome measures

Measure	RIV4 n=190 Participants Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)	IIV4 n=192 Participants Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.
Number of Pregnant Women With Fetal or Neonatal Death After RIV4 Versus IIV4 Vaccination	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Birth outcomes were monitored through 19 weeks 6 days gestation.

Population: mITT Population- any participant that was enrolled, randomized into the study, and received study vaccine. By definition, SAB can only occur in women that are at less than 20 weeks 0 days gestational age. All women that were at or over 20 weeks 0 days gestational age were removed from this analysis.

Spontaneous abortion (SAB) is defined as pregnancy loss prior to 20 weeks 0 days.

Outcome measures

Measure	RIV4 n=62 Participants Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)	IIV4 n=72 Participants Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.
Number of Pregnant Women With Spontaneous Abortion After RIV4 Versus IIV4 Vaccination	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Reactogenicity was measured for 8 days post-vaccination.

Population: mITT Population- any participant that was enrolled, randomized into the study, and received study vaccine

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.

Outcome measures

Measure	RIV4 n=190 Participants Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)	IIV4 n=192 Participants Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Injection Site Pain	16 Participants	14 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Injection Site Redness	2 Participants	1 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Injection Site Tenderness	16 Participants	22 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Injection Site Swelling	0 Participants	0 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Nausea	7 Participants	13 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Vomiting	5 Participants	8 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Diarrhea	6 Participants	6 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Abdominal Pain	4 Participants	5 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Headache	11 Participants	20 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Chills/Shivering	3 Participants	3 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Body Rash	0 Participants	1 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Fever	0 Participants	0 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Malaise (Fatigue)	11 Participants	12 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Myalgia (Body Aches)	7 Participants	8 Participants
Number of Pregnant Women With Moderate/Severe Solicited Reactogenicity Events (Local and Systemic) Within 8 Days After Vaccination With RIV4 Versus IIV4 Joint Pain	5 Participants	7 Participants

Adverse Events

RIV4

Serious events: 14 serious events

Other events: 22 other events

Deaths: 2 deaths

IIV4

Serious events: 12 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	RIV4 n=190 participants at risk Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)	IIV4 n=192 participants at risk Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.
General disorders Opioid Dependence Relapse	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Pregnancy, puerperium and perinatal conditions Vaginal Bleeding	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Pregnancy, puerperium and perinatal conditions Preeclampsia	2.6% 5/190 • Number of events 5 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	1.6% 3/192 • Number of events 3 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Pregnancy, puerperium and perinatal conditions Spontaneous Abortion	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	1.0% 2/192 • Number of events 2 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Gastrointestinal disorders Vomiting	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Pregnancy, puerperium and perinatal conditions Retained Products of Conception	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Gastrointestinal disorders Appendicitis	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Infections and infestations Infection	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Vascular disorders Hypertension	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Pregnancy, puerperium and perinatal conditions Chorioamnionitis	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Respiratory, thoracic and mediastinal disorders Shortness of Breath	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Pregnancy, puerperium and perinatal conditions Volume Overload	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Gastrointestinal disorders Enterocolitis with abdominal abscess	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Pregnancy, puerperium and perinatal conditions Intrauterine Fetal Demise	1.1% 2/190 • Number of events 2 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Pregnancy, puerperium and perinatal conditions Preterm Premature Rupture of Membranes (PPROM)	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Respiratory, thoracic and mediastinal disorders Bilateral Subsegmental Pulmonary Embolism	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Vascular disorders Retroperitoneal hematoma	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Congenital Fetal Cardiac Defect	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Bilateral pyelectasis	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Bladder outlet obstruction	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders ureterocele	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Supernumerary Digit- Left Hand	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Trisomy 21	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders ventricular septal defect	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	1.0% 2/192 • Number of events 2 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Ectopic kidney	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Absent thyroid	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Short femur	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Atrial septal defect	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders anomalous S1 hemivertebra	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Sagittal Synostosis	0.00% 0/190 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.52% 1/192 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Congenital, familial and genetic disorders Pyloric stenosis	0.53% 1/190 • Number of events 1 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	0.00% 0/192 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.

Other adverse events

Measure	RIV4 n=190 participants at risk Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4)	IIV4 n=192 participants at risk Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval.
General disorders Injection Site Pain	8.4% 16/190 • Number of events 16 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	7.3% 14/192 • Number of events 14 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
General disorders Injection Site Tenderness	8.4% 16/190 • Number of events 16 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	11.5% 22/192 • Number of events 22 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
Gastrointestinal disorders Nausea	3.7% 7/190 • Number of events 7 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	6.8% 13/192 • Number of events 13 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
General disorders Headache	5.8% 11/190 • Number of events 11 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	10.4% 20/192 • Number of events 20 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.
General disorders Malaise (Fatigue)	5.8% 11/190 • Number of events 11 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.	6.2% 12/192 • Number of events 12 • Adverse events were collected 8 days post vaccination. Serious adverse events were collected up to 90 days post-delivery. While there were 3 cases of spontaneous abortions, these are not counted as deaths and thus are not entered under "All-Cause Mortality." These are accounted for under "Serious Adverse Events." No pregnant women died during this study. The 2 deaths in the RIV4 group were both fetal deaths.

Additional Information

Dr. Geeta Swamy

Duke University

Phone: 919.681.5220

Email: geeta.swamy@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place