Field Trial of Maternal Influenza Immunization in Asia

Influenza Human Clinical Trial

— Mothers'Gift  

Official title:

Field Trial of Maternal Influenza Immunization in Asia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01034254
• Other study ID #: Mothers'Gift 241 Field Trial
• Status: Completed
• Phase: Phase 3
• Start date: November 2010
• Est. completion date: October 2017

Study information

• Verified date: January 2022
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3693
• Est. completion date: October 2017
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 15 Years to 45 Years

Eligibility

Inclusion Criteria:

• mid to late pregnancy

Exclusion Criteria:

• do not intend to deliver in the study area

• previous pregnancy in this study

Related Conditions & MeSH terms

• Influenza Human
• Influenza, Human

Intervention

Biological:
• influenza vaccine
Pregnant women will receive FDA approved influenza vaccine.
• saline placebo
Vaccination of pregnant women with saline placebo.

Locations

Country	Name	City	State
Nepal	Institute of Medicine, Tribhuvan Univerisity	Kathmandu

Sponsors (6)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Bill and Melinda Gates Foundation, Johns Hopkins Bloomberg School of Public Health, Seattle Children's Hospital, Thrasher Research Fund, Tribhuvan University, Nepal

Country where clinical trial is conducted

Nepal, 

References & Publications (12)

Cox S, Posner SF, McPheeters M, Jamieson DJ, Kourtis AP, Meikle S. Hospitalizations with respiratory illness among pregnant women during influenza season. Obstet Gynecol. 2006 Jun;107(6):1315-22. — View Citation

Dodds L, McNeil SA, Fell DB, Allen VM, Coombs A, Scott J, MacDonald N. Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women. CMAJ. 2007 Feb 13;176(4):463-8. — View Citation

Englund JA. Maternal immunization with inactivated influenza vaccine: rationale and experience. Vaccine. 2003 Jul 28;21(24):3460-4. Review. — View Citation

Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, Bresee JS, Cox NS; Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices (ACIP). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. 2008 Aug 8;57(RR-7):1-60. — View Citation

Greenwood B. Maternal immunisation in developing countries. Vaccine. 2003 Jul 28;21(24):3436-41. Review. — View Citation

Healy CM, Baker CJ. Maternal immunization. Pediatr Infect Dis J. 2007 Oct;26(10):945-8. Review. — View Citation

Lawn JE, Cousens S, Zupan J; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005 Mar 5-11;365(9462):891-900. — View Citation

MacDonald NE, Riley LE, Steinhoff MC. Influenza immunization in pregnancy. Obstet Gynecol. 2009 Aug;114(2 Pt 1):365-368. doi: 10.1097/AOG.0b013e3181af6ce8. — View Citation

Mak TK, Mangtani P, Leese J, Watson JM, Pfeifer D. Influenza vaccination in pregnancy: current evidence and selected national policies. Lancet Infect Dis. 2008 Jan;8(1):44-52. Review. — View Citation

Pickering LK, Baker CJ, Freed GL, Gall SA, Grogg SE, Poland GA, Rodewald LE, Schaffner W, Stinchfield P, Tan L, Zimmerman RK, Orenstein WA; Infectious Diseases Society of America. Immunization programs for infants, children, adolescents, and adults: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Sep 15;49(6):817-40. doi: 10.1086/605430. Erratum in: Clin Infect Dis. 2009 Nov 1;49(9):1465. — View Citation

Tamma PD, Ault KA, del Rio C, Steinhoff MC, Halsey NA, Omer SB. Safety of influenza vaccination during pregnancy. Am J Obstet Gynecol. 2009 Dec;201(6):547-52. doi: 10.1016/j.ajog.2009.09.034. Epub 2009 Oct 21. Review. — View Citation

Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, Wilson E, Omer SB, Shahid NS, Breiman RF, Steinhoff MC. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med. 2008 Oct 9;359(15):1555-64. doi: 10.1056/NEJMoa0708630. Epub 2008 Sep 17. Erratum in: N Engl J Med. 2009 Feb 5;360(6):648.. Breiman, Robert E [corrected to Breiman, Robert F]. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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