Influenza Vaccine in Pregnant Women - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00905125

Purpose

In pregnant women, flu may cause complications like pneumonia (infection of the lungs) or hospitalization. In the United States (US) it is recommend that all women get flu vaccine if they are going to be pregnant or deliver during the flu season but only a few studies have measured a pregnant woman's immune response (the body's defense against the flu) after getting the flu vaccine. About 200, 18-39 year old, inclusive, pregnant women in their second or third trimester (from 14 weeks of gestation to term, inclusive) will be enrolled in this US based study. Participation will be about 8 months in duration. Women will be randomized (assigned by chance) to receive either Fluzone® or Fluarix®. Blood collection will occur on Day 0 and 28 days post vaccination.

Condition	Intervention	Phase
Influenza	Biological: Fluarix® Biological: Fluzone®	Phase II

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Double-Blind Trial on the Safety and Immunogenicity of Inactivated Trivalent Influenza Vaccine in Pregnant Women

Resource links provided by NLM:

MedlinePlus related topics: Flu

Drug Information available for: Fluvirin Influenza Vaccines

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Proportion of subjects achieving a serum HAI antibody titer greater than or equal to 40 against each antigen included in the 2008-2009 seasonal inactivated TIV. [ Time Frame: Day 28 after receiving single dose. ] [ Designated as safety issue: No ]
Frequency of unsolicited non-serious adverse events (AEs) associated with vaccination. [ Time Frame: Day 0 through day 28 post vaccination. ] [ Designated as safety issue: Yes ]
Pregnancy outcome data: incidence of maternal and neonatal complications. [ Time Frame: At time of delivery. ] [ Designated as safety issue: Yes ]
Incidence of maternal serious adverse events (SAE). [ Time Frame: Through 6 months post vaccination. ] [ Designated as safety issue: Yes ]
Frequency and severity of maternal injection site and systemic reactions. [ Time Frame: Following a single 0.5 mL dose of the 2008-2009 seasonal inactivated trivalent influenza vaccine (Day 0) in the 7 days after vaccination. ] [ Designated as safety issue: Yes ]
Hemagglutination inhibition assay (HAI) geometric mean titer (GMT), frequency of 4-fold or greater increases in HAI antibody titer. [ Time Frame: Day 28 after receiving a single dose of 2008-2009 seasonal inactivated trivalent influenza vaccine (TIV). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of subjects achieving a serum microneutralization antibody titer of greater than or equal to 40 against each antigen in the 2008-2009 TIV. [ Time Frame: Day 28 after receiving a single dose. ] [ Designated as safety issue: No ]
Microneutralization (MN) geometric mean titer (GMT), frequency of 4-fold or greater increases in MN antibody titer. [ Time Frame: Day 28 after receiving a single dose of the 2008-2009 inactivated trivalent influenza vaccine. ] [ Designated as safety issue: No ]

Enrollment:	103
Study Start Date:	June 2009
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm 1, Fluzone®: Experimental Single 0.5 mL intramuscular injection of Fluzone®.	Biological: Fluzone® Single 0.5 mL injection of the 2008-2009 seasonal inactivated trivalent influenza vaccine administered intramuscularly in the deltoid. Fluzone® does not contain thimerosal.
Arm 2, Fluarix®: Experimental Single 0.5 mL intramuscular injection of Fluarix®.	Biological: Fluarix® Single 0.5 mL injection of the 2008-2009 seasonal inactivated trivalent influenza vaccine administered intramuscularly in the deltoid. Fluarix® contains less than 1 microgram (trace or a very small amount) thimerosal per shot.

Detailed Description:

Influenza is a significant cause of morbidity and mortality in the United States (US), resulting in an average of 226,000 hospitalizations and 36,000 deaths each year. Pregnant women and infants are at an increased risk for the complications of influenza. Severe disease, emergency department visits and hospitalizations occur frequently in pregnant women and infants which are considered high risk populations. In the US, routine vaccination with inactivated trivalent influenza vaccine (TIV) is recommended for pregnant women or those who deliver during the influenza season. Few studies exist on the safety and immunogenicity of administration of seasonal inactivated TIV despite long-standing recommendations. Although influenza vaccination has been recommended during pregnancy, the rates of immunization remain low, at about 13 percent. This is a multi-site randomized, double-blind clinical trial in 200 ambulatory, medically stable 18-39 year old, inclusive, pregnant women in their second or third trimester of pregnancy (from 14 weeks of gestation to term, inclusive). Study subjects will be randomized 1:1 to receive one dose of a 2008-2009 seasonal inactivated TIV, either Fluzone® or Fluarix® (100 pregnant women per vaccine group). Once enrolled, a blood sample will be collected and each subject will receive a single 0.5 mL dose of a 2008-2009 seasonal inactivated TIV, either Fluzone® or Fluarix®. The vaccination will occur on Day 0. Subjects will be observed for approximately 15 minutes after vaccination. All subjects will maintain a memory aid recording oral temperature, and systemic and local adverse events (AEs) for 7 days after each vaccination. Subjects will be encouraged to take their temperature around the same time each day. Subjects will have a phone call on Day 2 for review of memory aid, concomitant medication assessment, and assessment of AEs. Subjects will have a phone call on Day 8 for AE assessment, concomitant medication assessment and review of memory aid. At approximately Day 28 after the vaccination, subjects will return to the clinic for immunogenicity blood sample collection, concomitant medication assessment, and assessment of any AEs. A targeted physical exam will be conducted, if indicated. At approximately Day 180 or 6 months after vaccination, subjects will have a phone call for assessment for any serious adverse events (SAEs). Unsolicited non-serious AE data will be captured Day 0 through Day 28. Maternal SAE data will be captured throughout the study period (Day 0 through Day 180, approximately 6 months after dose of vaccine). Maternal and infant SAE data will be collected when obtaining data on pregnancy outcome. Serum for immunogenicity evaluations will be obtained prior to the dose of vaccine (at Day 0); and one month after vaccination (at Day 28). Pregnancy outcome data will be captured by a review of medical records and a phone call to the subject. Data include any complications during labor and delivery for both the mother as well as the neonate, to include premature delivery or delivery by emergency cesarean section. Neonatal assessments will include but not be limited to gestational age, birth weight, Apgar scores, congenital abnormalities, infection, hematological and metabolic complications, admission to nursery or Neonatal Intensive Care Unit and the need for respiratory support. Blood samples collected will be tested in a central laboratory for the levels of hemagglutination inhibition (HAI) and microneutralization (MN) antibodies.

Eligibility

Ages Eligible for Study:	18 Years to 39 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Pregnant female between the ages of 18 and 39 years, inclusive.
Is from 14 weeks of gestation to term, inclusive.
Is in good health, as determined by vital signs (heart rate <100 bpm; blood pressure: systolic <140 mm Hg; diastolic less than or equal to 90 mm Hg; oral temperature <100.0 degrees Fahrenheit), medical history to ensure stable medical condition and a targeted physical examination based on medical history (if indicated). A stable medical condition is defined as health outcomes of the specific disease are considered to be within acceptable limits in the last 3 months.
Able to understand and comply with planned study procedures.
Provides written informed consent prior to initiation of any study procedures.
Agrees to sign medical release for herself and her infant(s) to allow study staff to gather pregnancy outcome data, if needed per clinical site policy.

Exclusion Criteria:

Receipt of the 2008-2009 seasonal influenza vaccine [trivalent inactivated vaccine (TIV) or Flumist] prior to enrollment into the study.
Has a known allergy to eggs, egg proteins, latex allergy or allergy to other components in the vaccines (i.e. formaldehyde, polyethylene glycol p-isooctylphenyl ether, sucrose, gelatin, polysorbate 80).
Has a history of severe reactions following immunization with contemporary influenza virus vaccines.
Has received any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to vaccination in this study or expects to receive a licensed product prior to Visit 4 (Day 28 visit) (except for inactivated influenza vaccine which may be received 2 weeks post vaccination with study product). Measles, mumps, rubella vaccine is permitted post-partum.
Has a moderate-to-severe acute illness and/or an oral temperature greater than or equal to 100.0 degrees Fahrenheit, within 72 hours prior to vaccination. (This may result in a temporary delay of vaccination).
Immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months.
Has an active neoplastic disease, a history of any hematologic malignancy, current bleeding disorder, or taking anticoagulants.
Long term use of oral or parenteral steroids, high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed) or has received steroids for treatment of pre-term labor during this pregnancy.
Has a history of receiving immunoglobulin or other blood product (with exception of Rhogam) within the 3 months prior to vaccination in this study.
Has a diagnosis of a current and uncontrolled major psychiatric disorder.
The subject is receiving listed psychiatric drugs (aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, trifluopromazine, chlorprothixene, chlorpromazine, perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate). Subjects who are receiving an antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study.
Known active human immunodeficiency virus, hepatitis B, or hepatitis C infection.
History of alcohol or drug abuse in the 1 year prior to enrollment.
Has a history of Guillain-Barré syndrome.
Has a seizure disorder or is on an anti-seizure medication for a seizure disorder.
Has received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) during this pregnancy prior to enrollment, or expects to receive an experimental/investigational agent prior to Visit 4 (Day 28 visit).
Has an acute or chronic medical condition that, in the opinion of the investigator would interfere with the evaluation of responses (this includes, but is not limited to: known chronic liver disease, significant renal disease, transplant recipients, uncontrolled diabetes, juvenile diabetes (Type 1) or advanced diabetes with renal and eye disease; diabetes controlled by diet or oral agents is acceptable).
Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00905125

Locations

United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Maryland
University of Maryland, Baltimore
Baltimore, Maryland, United States, 21201
United States, Missouri
Saint Louis University
St. Louis, Missouri, United States, 63104
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Group Health Cooperative
Seattle, Washington, United States, 98101

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

More Information

No publications provided

Responsible Party:	HHS/NIAID/DMID ( Robert Johnson )
Study ID Numbers:	09-0033
Study First Received:	May 18, 2009
Last Updated:	February 4, 2010
ClinicalTrials.gov Identifier:	NCT00905125 History of Changes
Health Authority:	United States: Institutional Review Board; United States: Food and Drug Administration; United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

influenza, trivalent, vaccine, pregnant women

Additional relevant MeSH terms:

Virus Diseases
RNA Virus Infections
Respiratory Tract Diseases

Respiratory Tract Infections
Influenza, Human
Orthomyxoviridae Infections

ClinicalTrials.gov processed this record on February 08, 2010