Influenza Vaccine in Pregnant Women

NCT00905125 | Completed Phase 2 Results

• 2 other identifiers: 09-0033N01AI80002C
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Influenza

Keywords

influenza, trivalent, vaccine, pregnant women

Outcome Measures

Primary Outcomes (11)

• Number of Participants With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer Greater Than or Equal to 40 Against Each Antigen Included in the 2008-2009 Seasonal Inactivated Trivalent Influenza Vaccine (TIV)

  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 2008-2009 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen.

  Day 0 prior to and Day 28 after receiving single dose.

• 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.

  At 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.

  At time of delivery.

• Number of Participants Reporting Serious Adverse Events (SAE)

  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. All events are included regardless of association to vaccination.

  Through 6 months post vaccination.

• Number of Participants Reporting Unsolicited Non-serious Adverse Events Considered Associated With Vaccination

  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.

  Day 0 through Day 28 post vaccination.

• Number of Participants Reporting Solicited Injection Site Reactions at Each Severity Based on the Functional Grading Scale

  Participants recorded a daily maximum severity at which local reactions of pain, tenderness and swelling were experienced. Mild reactions had no interference with daily activities, moderate reactions interfered with daily activity, and severe reactions were defined as preventing daily activity. Participants are reported at the highest severity experienced across the 8 days.

  Days 0-7 after vaccination.

• Number of Participants Reporting Measured Injection Site Reactions of Swelling and Redness at Each Grade

  Participants recorded a daily measured value of swelling and redness, if present. The protocol defined grading of small, medium and large, with small as less than 20 mm, medium as 20-50 mm and large as greater than 50 mm. Participants are counted at the largest measured grade experienced across the 8 day period after vaccination.

  Days 0-7 after vaccination.

• Number of Participants Reporting Solicited Systemic Symptoms at Each Severity Based on the Functional Grading Scale

  Participants recorded a daily maximum severity at which systemic symptoms of feverishness, malaise, myalgia, headache and nausea were experienced. Mild reactions had no interference with daily activities, moderate reactions interfered with daily activity, and severe reactions were defined as preventing daily activity. Participants are reported at the highest severity experienced across the 8 days.

  Days 0-7 after vaccination.

• Number of Participants Reporting Fever Based on the Protocol-defined Grading Scale for Oral Temperature

  Participants recorded a daily oral temperature on a memory aid for 8 days (Days 0-7) after vaccination. The protocol defined mild fever as oral temperatures 37.8 to less than 38 degree Celsius, moderate fever as 38 to less than 39 degrees Celsius and severe fever as oral temperatures of 39 degrees Celsius or higher. Participants are reported at the highest severity experienced across the 8 days.

  Days 0-7 after vaccination.

• Hemagglutination Inhibition Assay (HAI) Geometric Mean Titer (GMT) Against Each Antigen in the 2008-2009 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 2008-2009 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen.

  Day 0 prior to and Day 28 after receiving single dose.

• Number of Participants With a Four-fold or Greater Rise in HAI Antibody Titer Against Each Antigen in the 2008-2009 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 2008-2009 seasonal inactivated TIV: Influenza B antigen, H1N1 antigen, and H3N2 antigen. A participant met the threshold of a four-fold increase in titer if the Day 0 titer was less than 10 (the assay's lowest level of detection) and the Day 28 titer was 40 or greater, or the Day 0 titer was greater than or equal to 10, and the Day 28 titer was an increase by four-fold or more.

  Day 0 prior to and Day 28 receiving a single dose.

Secondary Outcomes (3)

• Number of Participants With a Serum Microneutralization Antibody Titer of Greater Than or Equal to 40 Against Each Antigen in the 2008-2009 TIV

  Day 0 prior to and Day 28 after receiving a single dose.

• Number of Participants With a Four-fold or Greater Rise in Microneutralization Antibody Titer Against Each Antigen in the 2008-2009 TIV

  Day 0 prior to and Day 28 receiving a single dose.

• Microneutralization Assay Geometric Mean Antibody Titers Against Each Antigen in the 2008-2009 TIV

  Day 0 prior to and Day 28 after receiving a single dose.

Study Arms (2)

Arm 2, Fluarix®

EXPERIMENTAL

Single 0.5 mL intramuscular injection of Fluarix®.

Biological: Fluarix®

Arm 1, Fluzone®

EXPERIMENTAL

Single 0.5 mL intramuscular injection of Fluzone®.

Biological: Fluzone®

Interventions

Fluzone® BIOLOGICAL

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 1, Fluzone®

Fluarix® BIOLOGICAL

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.

Arm 2, Fluarix®

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (9)

Emory University School of Medicine - Gynecology and Obstetrics

Atlanta, Georgia, 30322, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Maryland Baltimore

Baltimore, Maryland, 21201, United States

Location

Mayo Clinic, Rochester - Vaccine Research Group

Rochester, Minnesota, 55905, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232-2573, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030, United States

Location

Group Health Cooperative

Seattle, Washington, 98101, United States

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; fluarix

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

In September of 2009, the trial was closed to enrollment prior to accruing the intended 200 participants due to the availability of the 2009-2010 seasonal Influenza vaccine and onset of Influenza season.

Results Point of Contact

• Title: Shital M. Patel, M.D.
• Organization: Medicine and Molecular Virology & Microbiology, Baylor College of Medicine

shitalp@bcm.edu

713-798-3793

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2009
• First Posted: May 20, 2009
• Study Start: June 1, 2009
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: June 13, 2012
• Results First Posted: April 6, 2011

Record last verified: 2010-03

Locations

US (9)