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| Name | Class |
|---|---|
| Children's Hospital Medical Center, Cincinnati | OTHER |
| Boston Medical Center | OTHER |
| Centers for Disease Control and Prevention | FED |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RIV4 | Experimental | The first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology |
|
| IIV4 | Active Comparator | Standard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Quadrivalent Recombinant Influenza Vaccine | Biological | The first recombinant inactivated influenza vaccine (RIV) using an insect baculovirus expression system and recombinant DNA technology |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| Birth outcomes were monitored within postnatal day 28. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Number of Pregnant Women With Fetal or Neonatal Death After RIV4 Versus IIV4 Vaccination |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Geeta K Swamy, MD | Duke University | Principal Investigator |
| Karen R Broder, MD | Centers for Disease Control and Prevention | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boston Medical Center | Boston | Massachusetts | 02118 | United States | ||
| Duke University Medical Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | IIV4 | Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval. |
| FG001 | RIV4 | Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants who received study product.
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| ID | Title | Description |
|---|---|---|
| BG000 | RIV4 | Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4) |
| BG001 | IIV4 | Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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:
| mITT Population- any participant that was enrolled, randomized into the study, and received study vaccine | Posted | Count of Participants | Participants | Birth outcomes were monitored within postnatal day 28. |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | RIV4 | Subjects in this group received an intramuscular injection of 0.5mL quadrivalent Recombinant Influenza Vaccine, Flublok (RIV4) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Opioid Dependence Relapse | General disorders | Systematic Assessment | Hospitalized due to relapse of opioid dependence |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection Site Pain | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Geeta Swamy | Duke University | 919.681.5220 | geeta.swamy@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 15, 2022 | Nov 30, 2022 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 19, 2022 | Nov 30, 2022 | SAP_003.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 21, 2020 | Apr 5, 2021 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
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| ID | Term |
|---|---|
| D007252 | Influenza Vaccines |
| C517981 | FluLaval |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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|
| Quadrivalent Inactivated Influenza Vaccine | Biological | Standard inactivated influenza vaccine (IIV) manufactured involving the use of embryonated hen eggs. |
|
|
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. |
| 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. |
| 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. |
| Durham |
| North Carolina |
| 27705 |
| United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Found to be ineligible |
|
| Intrauterine fetal demise (IUFD) |
|
| Spontaneous abortion (SAB) |
|
| Elective termination |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Gestational Age at Enrollment | Count of Participants | Participants |
|
| Receipt of prior influenza season vaccine | Count of Participants | Participants |
|
| OG001 | IIV4 | Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval. |
|
|
|
| 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. | mITT Population- any participant that was enrolled, randomized into the study, and received study vaccine | Posted | Count of Participants | Participants | 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. | mITT Population- any participant that was enrolled, randomized into the study, and received study vaccine | Posted | Count of Participants | Participants | 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. | 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. | Posted | Count of Participants | Participants | 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. | mITT Population- any participant that was enrolled, randomized into the study, and received study vaccine | Posted | Count of Participants | Participants | Reactogenicity was measured for 8 days post-vaccination. |
|
|
|
|
| 2 |
| 190 |
| 14 |
| 190 |
| 22 |
| 190 |
| EG001 | IIV4 | Subjects in this group received an intramuscular injection of 0.5mL standard quadrivalent Inactivated Influenza vaccine (IIV4), Flulaval. | 0 | 192 | 12 | 192 | 22 | 192 |
|
| Vaginal Bleeding | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Preeclampsia | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Spontaneous Abortion | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Retained Products of Conception | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Appendicitis | Gastrointestinal disorders | Systematic Assessment | Resulted in a laparoscopic appendectomy |
|
| Infection | Infections and infestations | Systematic Assessment | Surgical site infection after laparoscopic appendectomy |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Chorioamnionitis | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Volume Overload | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Enterocolitis with abdominal abscess | Gastrointestinal disorders | Systematic Assessment |
|
| Intrauterine Fetal Demise | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Preterm Premature Rupture of Membranes (PPROM) | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Bilateral Subsegmental Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Retroperitoneal hematoma | Vascular disorders | Systematic Assessment |
|
| Congenital Fetal Cardiac Defect | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Bilateral pyelectasis | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Bladder outlet obstruction | Congenital, familial and genetic disorders | Systematic Assessment | Including hydronephrosis due to obstruction of bladder, Hydroureter, Chronic kidney disease |
|
| ureterocele | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Supernumerary Digit- Left Hand | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Trisomy 21 | Congenital, familial and genetic disorders | Systematic Assessment |
|
| ventricular septal defect | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Ectopic kidney | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Absent thyroid | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Short femur | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Atrial septal defect | Congenital, familial and genetic disorders | Systematic Assessment |
|
| anomalous S1 hemivertebra | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Sagittal Synostosis | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Pyloric stenosis | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Injection Site Tenderness | General disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Malaise (Fatigue) | General disorders | Systematic Assessment |
|
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| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
| Injection Site Tenderness |
|
| Injection Site Swelling |
|
| Nausea |
|
| Vomiting |
|
| Diarrhea |
|
| Abdominal Pain |
|
| Headache |
|
| Chills/Shivering |
|
| Body Rash |
|
| Fever |
|
| Malaise (Fatigue) |
|
| Myalgia (Body Aches) |
|
| Joint Pain |
|
Injection Site Redness |
| Mantel Haenszel |
| 0.6217 |
| Odds Ratio (OR) |
| 2.03 |
| 2-Sided |
| 95 |
| 0.18 |
| 22.52 |
| Superiority |
These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Injection Site Tenderness | Mantel Haenszel | 0.3848 | Odds Ratio (OR) | 0.70 | 2-Sided | 95 | 0.35 | 1.39 | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Nausea | Mantel Haenszel | 0.2504 | Odds Ratio (OR) | 0.53 | 2-Sided | 95 | 0.21 | 1.35 | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Vomiting | Mantel Haenszel | 0.5751 | Odds Ratio (OR) | 0.62 | 2-Sided | 95 | 0.20 | 1.93 | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Diarrhea | Mantel Haenszel | 1.0000 | Odds Ratio (OR) | 1.01 | 2-Sided | 95 | 0.32 | 3.19 | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Abdominal Pain | Mantel Haenszel | 1.0000 | Odds Ratio (OR) | 0.80 | 2-Sided | 95 | 0.21 | 3.04 | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Headache | Mantel Haenszel | 0.1326 | Odds Ratio (OR) | 0.53 | 2-Sided | 95 | 0.25 | 1.13 | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Chills/Shivering | Mantel Haenszel | 1.0000 | Odds Ratio (OR) | 1.01 | 2-Sided | 95 | 0.20 | 5.04 | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Body Rash | Mantel Haenszel | 1.0000 | Odds Ratio (OR) | 0.00 | 2-Sided | 95 | 0.00 | The upper limit of this CI is infinity, thus no numeric value can be provided. | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Malaise (Fatigue) | Mantel Haenszel | 1.0000 | Odds Ratio (OR) | 0.92 | 2-Sided | 95 | 0.39 | 2.15 | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Myalgia (Body Aches) | Mantel Haenszel | 1.0000 | Odds Ratio (OR) | 0.87 | 2-Sided | 95 | 0.31 | 2.48 | Superiority | These proportions will be compared between the RIV4 group and the IIV4 group, within symptom, using an exact Mantel-Haenszel statistic (calculated in Proc Logistic in SAS) in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. |
| Joint Pain | Mantel Haenszel | 0.7704 | Odds Ratio (OR) | 0.71 | 2-Sided | 95 | 0.22 | 2.29 | Superiority |