Evaluate the Immunogenicity and Safety of the 2011-2012 Vaccine Against Seasonal Influenza on Pregnant Women

Study Overview
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Brief Summary
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The hypothesis proposed in this study is that the 2011-2012 Seasonal Influenza Vaccine (including H3N2 and H1N1 subtypes of serotype A strain over the serotype B) administered to 15ug (without adjuvant) via intramuscular in pregnant women will be safe and immunogenic.

Detailed Description
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Despite the fact that influenza vaccination of pregnant women is amply recommended, coverage of influenza vaccination is low. In general, there are few studies on safety of the vaccine to this group, particularly during the first three months of pregnancy or evaluating trivalent vaccines containing inactivated pandemic 2009 H1N1 virus. Studies are controversial regarding passage of maternal antibodies and protection to the newborn. The investigators propose to evaluate safety and immunogenicity of 2011-2012 seasonal trivalent influenza vaccine (Northern hemisphere)(containing an A/California/7/2009 (H1N1)-like virus; an A/Perth/16/2009 (H3N2)-like virus; a B/Brisbane/60/2008-like virus) produced by Sanofi Pasteur. Study design is a Phase II/III, two arm, non-randomized clinical trial. The investigators will recruit 120 pregnant women, 18 to 39 years of age, 14 to 34 week pregnant and 120 non-pregnant women. Trivalent influenza vaccine (0.5ml) will be administered IM in the deltoid zone. Participants will be observed for 30 min post-vaccination for acute adverse reactions and periodically during the 60 days post-vaccination for reactogenicity, adverse effects and severe adverse effects. Baseline and 28 day influenza antibodies will be measured by hemagglutination and microneutralization. Umbilical cord blood (10ml) will be drawn during delivery. Newborns will be followed monthly for growth and morbidity up to six months of age. If necessary, they will be referred for appropriate clinical care. Main outcome will be seroconversion and seroresponse at 28 days post vaccination. Results will be adjusted by study group and other relevant covariables.Safety will be analyzed according to type, severity and study group.

Official Title
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Clinical Trial to Evaluate the Immunogenicity and Safety of the 2011-2012 Vaccine Against Seasonal Influenza on Pregnant Women

Conditions
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Pregnancy, Investigation or Care in A Nonpregnant Woman

Intervention / Treatment
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* Biological: Seasonal influenza vaccination


Participation Criteria
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Eligibility Criteria
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I.Selection Criteria in pregnant women I.a.Inclusion Criteria Pregnant women aged 18 to 39 years Have made at least one prenatal visit to confirm the pregnancy Available for follow-up time To be from 14 to 34 weeks of gestation If recruitment is conducted between August and November 2011, patient could have Received the Seasonal Influence Vaccine from previous period, but not the H1N1 vaccine Agree to participate in the study and provide informed consent Good health according to the clinical evaluation of the participant, confirming: heart Rate less than 100', systolic blood pressure less than 140 mm Hg, and diastolic less or Equal than 90 mmHg, and oral temperature less or equal than 37.4° C Normal physical exam and laboratory test within 28 days prior to recruitment HIV-negative test I. b.Exclusion criteria Preeclampsia or eclampsia Treatment with immunosuppressive drugs Receipt of blood products, 120 days prior to HIV screening Receipt of immunoglobulin 60 days prior to screening for HIV Have received live attenuated vaccines 30 days prior of vaccination Have received inactivated vaccines within 14 days prior to vaccination Treatment of latent or active tuberculosis Autoimmune disease or immunodeficiency Contraindication to receiving seasonal influenza vaccine Vaccine side effects History of angioedema. Unstable asthma Diabetes Thyroidectomy or thyroid disease in the last 12 months Idiopathic urticaria Hypertension not well-controlled with treatment Medically diagnosed bleeding diathesis, coagulopathy or platelet disorder Active malignant tumor or in not-effective treatment Asplenia Allergic reaction to antibiotics Guillain Barre Psychiatric condition that difficult adherence to protocol II.Selection criteria in nonpregnant woman II. a.Inclusion criteria Nonpregnant woman aged 18 to 39 years Negative pregnancy test 24 hours prior to administration of the vaccine Agree to participate in the study and provide informed consent Good health according to the clinical evaluation of participant, confirming: heart rate less than 100 ', systolic blood pressure less than 140 mmHg, diastolic less than or equal to 90 mmHg, and oral temperature less than or equal to 37.4°C Normal physical exam and laboratory test within 28 days prior to recruitment HIV-negative test Agree to not get pregnant during the study and follow an effective contraceptive method Good health, determined this by history Receive the seasonal influenza vaccine at least two weeks prior to inclusion in this study II. b.Exclusion criteria Being in treatment with immunosuppressive drugs Receipt of blood products, 120 days prior to HIV screening Receipt of immunoglobulin 60 days prior to screening for HIV Have received live attenuated vaccines 30 days of vaccination Have received inactivated vaccines within 14 days prior to vaccination Treatment of latent or active tuberculosis Autoimmune disease or immunodeficiency Contraindication to receiving seasonal influenza vaccine Vaccine side effects History of angioedema Unstable asthma Diabetes Type 2 Thyroidectomy or thyroid disease requiring treatment in the past 12 months. Idiopathic urticaria Hypertension not well-controlled with treatment Medically diagnosed bleeding diathesis, coagulopathy or platelet disorder Active malignant tumor Convulsive condition Anatomic or functional asplenia Allergic reaction to antibiotics Guillain Barre Psychiatric condition

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregnant Woman<br>Pregnant Woman | Biological: Seasonal influenza vaccination<br>* 2011-2012 Seasonal Trivalent Inactivated Influenza Vaccine (include A/California/7/2009 (H1N1)-like, A/Perth/16/2009 (H3N2)-like, and B/Brisbane/60/2008-like antigens) administered to 15ug without adjuvant, via intramuscular in pregnant and nonpregnant women. It is recommended that vaccines for use in the 2012-2013 influenza season (northern hemisphere winter) contain the following: an A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; a B/Wisconsin/1/2010-like virus.<br>* Other names: Be recruited and will continue in parallel both groups;|
| Experimental: Nonpregnant women<br>2011-2012 Seasonal Influenza Vaccine (include A/California/7/2009 (H1N1)-like, A/Perth/16/2009 (H3N2)-like, and B/Brisbane/60/2008-like antigens) administered to 15ug without adjuvant, via intramuscular in pregnant and nonpregnant women. | Biological: Seasonal influenza vaccination<br>* 2011-2012 Seasonal Trivalent Inactivated Influenza Vaccine (include A/California/7/2009 (H1N1)-like, A/Perth/16/2009 (H3N2)-like, and B/Brisbane/60/2008-like antigens) administered to 15ug without adjuvant, via intramuscular in pregnant and nonpregnant women. It is recommended that vaccines for use in the 2012-2013 influenza season (northern hemisphere winter) contain the following: an A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; a B/Wisconsin/1/2010-like virus.<br>* Other names: Be recruited and will continue in parallel both groups;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | The results of this analysis will determine whether the vaccine provides protection based on the immunogenicity provided by the vaccine. They identify specific antibodies against influenza virus A (H1N1), will carry out the serological techniques by hemagglutination inhibition and microneutralization. The immunogenicity analysis will be measured by seroconversion and seroresponse | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Monitoring of pregnant women will be at monthly intervals until the time of the birth. Pregnant women and nonpregnant are going to be monitored for 30 min after vaccination to monitor immediate clinical reactions, and at 28 days after completing a self-registration of possible events associated with vaccination, as well as follow-up home visits on days 1, 3, 5, 7, 11, 15, 21, and 28. At day 28, will be made a complete clinical evaluation and blood sampling for assessment of immunogenicity. | 30 minutes immediate, day 1, 3, 5,7,11, 15 and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccination, Influenza, Immunogenicity, Safety