Field Trial of Maternal Influenza Immunization in Asia

Study Overview
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Brief Summary
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This project is designed to assess the efficacy of immunizing women during pregnancy with influenza vaccine on the health of these women during their pregnancy and for 6 months post-partum as well as on the health of their newborn infants during the first 6 months of life. It will be conducted in Sarlahi District in southern Nepal, a rural area where a number of large scale randomized trials have been conducted over the past 20 years.

Detailed Description
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This is a community-based, placebo-controlled, individually randomized trial in trial among women who are or who become pregnant in 9 Village Development Committees in Sarlahi District, Nepal. The study population for this trial will include all women who are identified as pregnant with gestational age between 17 and 34 weeks gestation during a 12-month period in 9 Village Development Committees (VDC) of Sarlahi District, Nepal. The 9 VDCs include: Dhungre Khola, Karmaiya, Hariaun, Ghurkauli, Sasapur, Netraganj, Lalbandi, Jabdi, and Raniganj. The vaccine that will be given will be the most current vaccine at the time of subject enrollment. That is, for women enrolled after October in either study cohort, the vaccine will be switched to the newly available vaccine for that year. The control group will be placebo (saline injection). The justification for the use of a placebo injection in this trial is as follows: There is only one trial (Bangladesh) that demonstrates efficacy of influenza vaccination in pregnancy on perinatal outcomes and respiratory morbidity in early infancy. One of the issues with that study is that it was not placebo controlled. The control in that study was adult pneumococcal vaccine. It could be that the Bangladesh study underestimated the impact of influenza vaccine because the mothers and infants receive some indirect protection from the pneumococcal vaccine. In addition, influenza vaccine is not part of national policy or recommendations in Nepal at the current time and Ministry of Health officials are very interested in the results of our study as they consider their immunization program expansion over the next few years.

Official Title
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Field Trial of Maternal Influenza Immunization in Asia

Conditions
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Influenza Human

Intervention / Treatment
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* Biological: influenza vaccine
* Biological: saline placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: mid to late pregnancy Exclusion Criteria: do not intend to deliver in the study area previous pregnancy in this study

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: influenza vaccine<br>Pregnant women assigned to the intervention group will receive one dose of seasonal influenza vaccine at the time of enrollment. The vaccine that will be given will be the current seasonal influenza recommended vaccine at the time of enrollment. | Biological: influenza vaccine<br>* Pregnant women will receive FDA approved influenza vaccine.<br>* Other names: VAXIGRIP®;|
| Placebo Comparator: saline placebo<br>Pregnant women assigned to the control group will receive one dose of placebo (normal saline). | Biological: saline placebo<br>* Vaccination of pregnant women with saline placebo.<br>* Other names: saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Field Trial of Maternal Influenza Immunization | To compare, in women randomized to receive either influenza vaccine or control during pregnancy and their infants (through 6 months of age) a) the incidence of influenza-like illness or lab-confirmed influenza episodes b) the distribution of causes of febrile illness and the incidence of clinic visits and hospitalizations c) the incidence of low birth weight, the distribution of birth weight and gestational age and the growth of infants. | 2 annual recruitment cycles coinciding with flu seasons | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Substudy #1: Transplacental Transfer of Influenza Antibody from Mother to Infant | To estimate the efficacy of maternal vaccination for producing an immune response in the mother and for passive antibody transfer to the infant. To determine if timing of vaccination during pregnancy or other maternal factors such as nutritional status are related to level of antibody transfer to the infant. To compare neutralizing antibody concentrations in breastmilk of women randomized to receive either influenza vaccine or control during pregnancy. | 2 annual recruitment cycles | 
| Substudy #2: Indirect Protection of Maternal Influenza Vaccination on Family Members | Specific Aim: To compare the indirect protection of influenza vaccine on influenza-like and influenza-specific febrile illness rates in families of study women. | 2 annual recruiting cycles | 
| Substudy #3: Hepatitis E Infection in Pregnancy | To estimate the prevalence of anti-hepatitis E immunoglobulin G in women of reproductive age in rural Nepal. To estimate the incidence of hepatitis E infection (anti-hepatitis E seroconversion) during pregnancy in rural Nepal. To estimate the disease to infection ratio among women who seroconvert. To evaluate biochemical correlates of clinical disease among women who seroconvert. To describe pregnancy outcomes (miscarriage, stillbirth, neonatal mortality, maternal mortality) associated with women identified with incident infection or acute hepatitis E disease. | 2 annual recruiting cycles | 
| Pertussis In Infants | Estimate the incidence of pertussis in infants under 6 months of age and the protection afforded by maternal antibody transfer to infants. | 2 annual rucruiting cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza, immunization, pregnancy, efficacy, pertussis, hepatitis E