Field Trial of Maternal Influenza Immunization in Asia

Phase 3

Completed

• Conditions: Influenza Human
• Interventions: Biological: saline placebo; Biological: influenza vaccine

• Registration Number: NCT01034254
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2009-12-16
• Study First Submitted QC: 2009-12-16
• Study First Posted: 2009-12-17
• Study Start: 2010-11
• Primary Completion: 2014-05
• Study Completion: 2017-10
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-18
• Last Update Posted: 2022-02-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 3693

Inclusion Criteria

• mid to late pregnancy

Exclusion Criteria

• do not intend to deliver in the study area
• previous pregnancy in this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
saline placebo	saline placebo	Pregnant women assigned to the control group will receive one dose of placebo (normal saline).
influenza vaccine	influenza vaccine	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.

Primary Outcome Measures

Name	Time	Method
Field Trial of Maternal Influenza Immunization	2 annual recruitment cycles coinciding with flu seasons	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Institute of Medicine, Tribhuvan Univerisity; 🇳🇵 Kathmandu, Nepal