The purpose of this study is to see how much antibody (proteins produced by the immune system that help fight infections) the body makes after getting a flu vaccine. Researchers will also look at how the body reacts to the flu vaccine and how it affects the babies of pregnant women. The study will enroll approximately 240 women ages 18-39 years, including 180 pregnant women in their second or third trimester of pregnancy (at least 14 weeks pregnant) and 60 non-pregnant women. Participants will be randomly (by chance) assigned to 1 of 3 vaccine groups. Each participant will receive one shot of a 2010-2011 flu season licensed vaccine. The vaccine will be given as an intramuscular injection (shot in the muscle) in the upper arm. Study procedures include pregnancy testing, blood draws, and memory aids. Patient participation may be up to 8 months. The information from this study will help guide researchers in developing flu vaccines for pregnant women.
Influenza is a significant cause of morbidity and mortality in the United States. Pregnant women and infants are at an increased risk for the complications of influenza. Pregnant women are considered a high risk population. In the United States, routine vaccination with inactivated trivalent influenza vaccine (TIV) for women who are pregnant or deliver during the influenza season is recommended. However, few studies exist on the safety and immunogenicity of administration of seasonal inactivated TIV. Although influenza vaccination has been recommended during pregnancy, the rates of immunization remain low, at about 13 percent, which partly reflects concern of safety among pregnant women and providers. It is important to gather prospective data on the safety and immunogenicity of inactivated TIV vaccine in pregnant women. This is a multi-site randomized, double-blinded clinical trial in 180 healthy 18-39 year old, pregnant women in their second or third trimester of pregnancy (from 14 weeks of gestation to 33 weeks/6 days gestation, inclusive) and 60 healthy 18-39 year old non-pregnant controls. Study subjects will be randomized 1:1:1 to receive one of the following three 2010-2011 seasonal inactivated trivalent influenza vaccines: Fluarix®, Agriflu®, or Fluzone® (60 pregnant women and 20 non-pregnant women per group). The study will begin enrollment when at least 2 of the 4 study products are available. Once enrolled, a blood sample will be collected and each subject will receive a single 0.5 mL dose of the assigned vaccine. Subjects will be observed for at least 15 minutes after immunization, and the subjects will maintain a memory aid to record oral temperature and systemic and local adverse events (AEs) for 8 days after immunization. Subjects will have a phone call on Day 2 and 8 for review of memory aid, concomitant medication assessment, and assessment of AEs. At approximately Day 28 post-vaccination, subjects will return to the clinic for blood sample collection, AE and concomitant medication assessment, and a targeted physical examination (if indicated). Pregnant subjects will also have scheduled phone calls from Day 28 until the time of delivery or Day 180, whichever is later, to assess for any new-onset chronic medical conditions, and pregnancy-related problems such as miscarriage or serious adverse events (SAEs) since the last visit. At approximately Day 180 post-vaccination, subjects will return to the clinic for blood sample collection and assessment of the receipt of any vaccines since the last visit. Subjects will be asked about any new-onset chronic medical conditions, SAEs since the last visit and pregnancy-related problems such as miscarriage (for the pregnant women cohort). The duration of the study will be approximately 6 months for the non-pregnant subjects and about 6-8 months for the pregnant subjects, depending on delivery date for the pregnant women. Pregnant subjects will have collection of maternal and cord blood at the time of delivery. Pregnant subjects will also have a phone call 1 month after delivery to assess for any new-onset chronic medical conditions or SAEs since the last visit. The primary objectives are to evaluate the safety of a single 0.5 mL intramuscular injection of the 2010-2011 inactivated TIV in pregnant women and to evaluate the immunogenicity of the 2010-2011 inactivated TIV in pregnant women by hemagglutination inhibition assay (HAI). The secondary objectives are to evaluate the persistence of antibodies to the 2010-2011 inactivated TIV in pregnant women at Day 180 and to assess the transfer of maternally derived antibody against viruses in the 2010-2011 inactivated TIV to infants bor
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
183
Three licensed 2010-2011 seasonal inactivated trivalent influenza vaccines. Single intramuscular 0.5 mL dose. Each vaccine is formulated to contain 45 micrograms (mcg) hemagglutinin (HA) per 0.5 mL dose. Thimerosal is a preservative used in some vaccines. Fluzone, Agriflu and Fluarix do not contain thimerosal. For Fluarix, the tip cap and rubber plunger of the needleless prefilled syringes contain dry natural latex rubber.
Three licensed 2010-2011 seasonal inactivated trivalent influenza vaccines. Single intramuscular 0.5 mL dose. Each vaccine is formulated to contain 45 micrograms (mcg) hemagglutinin (HA) per 0.5 mL dose. Thimerosal is a preservative used in some vaccines. Fluzone, Agriflu and Fluarix do not contain thimerosal. For Fluarix, the tip cap and rubber plunger of the needleless prefilled syringes contain dry natural latex rubber..
Three licensed 2010-2011 seasonal inactivated trivalent influenza vaccines. Single intramuscular 0.5 mL dose. Each vaccine is formulated to contain 45 micrograms (mcg) hemagglutinin (HA) per 0.5 mL dose. Thimerosal is a preservative used in some vaccines. Fluzone®, Agriflu® and Fluarix® do not contain thimerosal. For Fluarix, the tip cap and rubber plunger of the needleless prefilled syringes contain dry natural latex rubber.
Saint Louis University - Center for Vaccine Development
St Louis, Missouri, United States
Duke University Medical Center - Duke Perinatal Clinic
Durham, North Carolina, United States
Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center
Nashville, Tennessee, United States
Baylor College of Medicine - Molecular Virology and Microbiology
Houston, Texas, United States
Group Health Research Institute - Seattle
Seattle, Washington, United States
Number of Participants Reporting Vaccine-associated Unsolicited Non-serious Adverse Events
Unsolicited non-serious adverse events were collected from participants at follow up contacts, either by phone or in clinic, through 28 days after vaccination. Association to vaccination was determined by a clinician licensed to make a medical diagnosis and listed on the site's Federal Drug Administration's Form 1572.
Time frame: Day 0 through Day 28 post vaccination
Number of Participants Reporting Maternal Complications of Pregnancy, Labor and Delivery
Participants were contacted after delivery, and medical records reviewed, to collect complications experienced during pregnancy, labor and delivery. The data collection process followed a prospectively-defined list of complications reported for this outcome measure, some of which may have also been reported as serious adverse events if otherwise meeting those requirements.
Time frame: During the pregnancy and at the time of delivery
Number of Participants Reporting Neonatal Complications
Participants were contacted after delivery, and medical records reviewed, to collect neonatal complications. The data collection process followed a prospectively-defined list of complications reported for this outcome measure, some of which may have also been reported as serious adverse events if otherwise meeting those requirements.
Time frame: At time of delivery
Number of Participants Reporting Vaccine-associated Serious Adverse Events (SAEs)
Serious adverse events included any untoward medical occurrence that resulted in death of the mother, fetus or infant; was life threatening to mother, fetus or infant; was a persistent/significant disability/incapacity; required in-patient hospitalization or prolongation thereof; was a congenital anomaly/birth defect in fetus or infant; or may have jeopardized the mother, fetus or infant, or required intervention to prevent one of the outcomes, or was described as Guillain-Barré Syndrome. Association was determined by a clinician licensed to diagnose and listed on the site's FDA Form 1572.
Time frame: Day 0 through Day 180 after vaccination
Number of Participants Reporting Solicited Subjective Local Reactions After Vaccination
Participants maintained a memory aid to record daily the occurrence of local reactions of pain, tenderness and swelling for 8 days after vaccination (Day 0-7) based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
Time frame: 8 days after vaccination (Days 0-7).
Number of Participants Reporting Solicited Quantitative Local Reactions After Vaccination
Participants maintained a memory aid to record daily the occurrence of local reactions of redness and swelling for 8 days after vaccination (Day 0-7). If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they reported experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
Time frame: 8 days after vaccination (Days 0-7).
Number of Participants Reporting Solicited Subjective Systemic Reactions After Vaccination
Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, and nausea for 8 days after vaccination (Day 0-7) based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
Time frame: 8 days after vaccination (Days 0-7).
Number of Participants Reporting Fever After Vaccination
Participants were provided with a thermometer and a memory aid on which to record daily oral temperatures for 8 days after vaccination (Day 0-7). The protocol defined fever as oral temperature of 37.8 degrees Celsius or higher. Participants are counted as experiencing fever if they reported oral temperatures of 37.8 degrees Celsius or higher on any of the 8 days.
Time frame: 8 days after vaccination (Days 0-7).
Hemagglutination Inhibition Assay (HAI) Geometric Mean Titer (GMT) Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine
Blood was collected for HAI assay at Day 0 prior to vaccination and again at 28 days following vaccination. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen.
Time frame: Day 0 prior to and Day 28 following vaccination
Number of Participants With 4-fold or Greater Serum HAI Antibody Titer Increases Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine
Blood was collected from all participants prior to vaccination as well as 28 days after vaccination. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 10 (the assay's lowest level of detection) and the Day 28 post vaccination titer was 40 or greater, or the Day 0 titer was greater than or equal to 10 and the Day 28 post vaccination titer was an increase by 4-fold or more.
Time frame: Day 0 prior to and Day 28 after vaccination
Number of Participants With HAI Antibody Titer of 40 or Greater Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine
Blood was collected from all participants prior to vaccination as well as 28 days after vaccination. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. Participants are counted if the titer at the timepoint is 40 or greater.
Time frame: Day 0 prior to and Day 28 after vaccination
Hemagglutination Inhibition Assay (HAI) Geometric Mean Titer (GMT) Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at 6 Months After Vaccination
Blood was collected for HAI assay at approximately Day 180 following vaccination. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen.
Time frame: Day 180 (approximately 6 months after vaccination)
Number of Participants With 4-fold or Greater Serum HAI Antibody Titer Increases Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at 6 Months After Vaccination
Blood was collected from all participants at 180 days after vaccination. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 10 (the assay's lowest level of detection) and the Day 180 post vaccination titer was 40 or greater, or the Day 0 titer was greater than or equal to 10 and the Day 180 post vaccination titer was an increase by 4-fold or more.
Time frame: Day 180 (approximately 6 months after vaccination)
Number of Participants With HAI Antibody Titer of 40 or Greater Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at 6 Months After Vaccination
Blood was collected from all participants at 180 days after vaccination. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. Participants are counted if the titer at the timepoint is 40 or greater.
Time frame: Day 180 (approximately 6 months after vaccination)
Maternal HAI GMT Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at Time of Delivery
Maternal blood was collected for HAI assay at time of delivery. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen.
Time frame: At time of delivery
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Number of Participants With 4-fold or Greater Maternal Serum HAI Antibody Titer Increases Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine at Time of Delivery
Blood was collected from all participants prior to vaccination as well as at time of delivery. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. A participant met the threshold of a 4-fold rise in titer if the Day 0 titer was less than 10 (the assay's lowest level of detection) and the titer was 40 or greater at delivery, or the Day 0 titer was greater than or equal to 10 and the titer was an increase by 4-fold or more at delivery.
Time frame: Day 0 prior to vaccination and at time of delivery
Number of Participants With a Maternal Serum HAI Antibody Titer Greater Than or Equal to 40 Against Each Antigen Included in the 2010-2011 Inactivated TIV at Time of Delivery.
Maternal blood was collected for HAI assay at time of delivery. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. Participants are counted if the titer at the timepoint is 40 or greater.
Time frame: At time of delivery
HAI GMT Against Each Antigen in the 2010-2011 Seasonal Influenza Trivalent Influenza Vaccine in Cord Blood Collected at Time of Delivery
Cord blood was collected at delivery for HAI assay at time of delivery. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen.
Time frame: At time of delivery
Number of Participants With HAI Antibody Titer Greater Than or Equal to 40 Against Each Antigen Included in the 2010-2011 Inactivated TIV in Cord Blood Collected at Time of Delivery.
Cord blood was collected at delivery for HAI assay at time of delivery. The HAI assay was conducted with the three antigens in the 2010-2011 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. Participants are counted if the titer at the timepoint is 40 or greater.
Time frame: At time of delivery