Field Trial of Maternal Influenza Immunization in Asia

NCT01034254 | Completed Phase 3 DMC

• 1 other identifier: Mothers'Gift 241 Field Trial
• Study Type: interventional
• Target: 3,693
• Locations: 1 country
• Sites: 1

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.

Conditions

Influenza Human

Keywords

influenza; immunization; pregnancy; efficacy; pertussis; hepatitis E

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Substudy #1: Transplacental Transfer of Influenza Antibody from Mother to Infant

  2 annual recruitment cycles

• Substudy #2: Indirect Protection of Maternal Influenza Vaccination on Family Members

  2 annual recruiting cycles

• Substudy #3: Hepatitis E Infection in Pregnancy

  2 annual recruiting cycles

• Pertussis In Infants

  2 annual rucruiting cycles

Study Arms (2)

influenza vaccine

EXPERIMENTAL

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

saline placebo

PLACEBO COMPARATOR

Pregnant women assigned to the control group will receive one dose of placebo (normal saline).

Biological: saline placebo

Interventions

influenza vaccine BIOLOGICAL

Pregnant women will receive FDA approved influenza vaccine.

Also known as: "VAXIGRIP®

influenza vaccine

saline placebo BIOLOGICAL

Vaccination of pregnant women with saline placebo.

Also known as: saline

saline placebo

Eligibility Criteria

• Age: 15 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• mid to late pregnancy

You may not qualify if:

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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Bill and Melinda Gates Foundation: collaborator
• Seattle Children's Hospital: collaborator
• Tribhuvan University, Nepal: collaborator
• Johns Hopkins Bloomberg School of Public Health: collaborator
• Thrasher Research Fund: collaborator

Study Sites (1)

Institute of Medicine, Tribhuvan Univerisity

Kathmandu, Nepal

Location

Related Publications (22)

• 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. doi: 10.1097/01.AOG.0000218702.92005.bb.

  PMID: 16738158 BACKGROUND

• 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. doi: 10.1503/cmaj.061435.

  PMID: 17296958 BACKGROUND

• Englund JA. Maternal immunization with inactivated influenza vaccine: rationale and experience. Vaccine. 2003 Jul 28;21(24):3460-4. doi: 10.1016/s0264-410x(03)00351-7.

  PMID: 12850360 BACKGROUND

• Greenwood B. Maternal immunisation in developing countries. Vaccine. 2003 Jul 28;21(24):3436-41. doi: 10.1016/s0264-410x(03)00346-3.

  PMID: 12850355 BACKGROUND

• Healy CM, Baker CJ. Maternal immunization. Pediatr Infect Dis J. 2007 Oct;26(10):945-8. doi: 10.1097/INF.0b013e318156c18c. No abstract available.

  PMID: 17901801 BACKGROUND

• 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. doi: 10.1016/S0140-6736(05)71048-5.

  PMID: 15752534 BACKGROUND

• 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. doi: 10.1016/S1473-3099(07)70311-0.

  PMID: 18156088 BACKGROUND

• 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.

  PMID: 18799552 BACKGROUND

• 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.

  PMID: 19622998 BACKGROUND

• 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.

  PMID: 19850275 BACKGROUND

• 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.

  PMID: 19659433 BACKGROUND

• 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.

  PMID: 18685555 BACKGROUND

• Regodon Wallin A, Tielsch JM, Khatry SK, Mullany LC, Englund JA, Chu H, LeClerq SC, Katz J. Nausea, vomiting and poor appetite during pregnancy and adverse birth outcomes in rural Nepal: an observational cohort study. BMC Pregnancy Childbirth. 2020 Sep 17;20(1):545. doi: 10.1186/s12884-020-03141-1.

  PMID: 32943001 DERIVED

• Omer SB, Clark DR, Madhi SA, Tapia MD, Nunes MC, Cutland CL, Simoes EAF, Aqil AR, Katz J, Tielsch JM, Steinhoff MC, Wairagkar N; BMGF Supported Maternal Influenza Immunization Trials Investigators Group. Efficacy, duration of protection, birth outcomes, and infant growth associated with influenza vaccination in pregnancy: a pooled analysis of three randomised controlled trials. Lancet Respir Med. 2020 Jun;8(6):597-608. doi: 10.1016/S2213-2600(19)30479-5.

  PMID: 32526188 DERIVED

• Clark DR, Omer SB, Tapia MD, Nunes MC, Cutland CL, Tielsch JM, Wairagkar N, Madhi SA; for BMGF Supported Maternal Influenza Immunization Trials Investigators Group. Influenza or Meningococcal Immunization During Pregnancy and Mortality in Women and Infants: A Pooled Analysis of Randomized Controlled Trials. Pediatr Infect Dis J. 2020 Jul;39(7):641-644. doi: 10.1097/INF.0000000000002629.

  PMID: 32379201 DERIVED

• Murray AF, Englund JA, Kuypers J, Tielsch JM, Katz J, Khatry SK, Leclerq SC, Chu HY. Infant Pneumococcal Carriage During Influenza, RSV, and hMPV Respiratory Illness Within a Maternal Influenza Immunization Trial. J Infect Dis. 2019 Aug 9;220(6):956-960. doi: 10.1093/infdis/jiz212.

  PMID: 31056697 DERIVED

• Katz J, Englund JA, Steinhoff MC, Khatry SK, Shrestha L, Kuypers J, Mullany LC, Chu HY, LeClerq SC, Kozuki N, Tielsch JM. Impact of Timing of Influenza Vaccination in Pregnancy on Transplacental Antibody Transfer, Influenza Incidence, and Birth Outcomes: A Randomized Trial in Rural Nepal. Clin Infect Dis. 2018 Jul 18;67(3):334-340. doi: 10.1093/cid/ciy090.

  PMID: 29452372 DERIVED

• Omer SB, Clark DR, Aqil AR, Tapia MD, Nunes MC, Kozuki N, Steinhoff MC, Madhi SA, Wairagkar N; for BMGF Supported Maternal Influenza Immunization Trials Investigators Group. Maternal Influenza Immunization and Prevention of Severe Clinical Pneumonia in Young Infants: Analysis of Randomized Controlled Trials Conducted in Nepal, Mali and South Africa. Pediatr Infect Dis J. 2018 May;37(5):436-440. doi: 10.1097/INF.0000000000001914.

  PMID: 29443825 DERIVED

• Katz J, Englund JA, Steinhoff MC, Khatry SK, Shrestha L, Kuypers J, Mullany LC, Chu HY, LeClerq SC, Kozuki N, Tielsch JM. Nutritional status of infants at six months of age following maternal influenza immunization: A randomized placebo-controlled trial in rural Nepal. Vaccine. 2017 Dec 4;35(48 Pt B):6743-6750. doi: 10.1016/j.vaccine.2017.09.095. Epub 2017 Oct 31.

  PMID: 29100709 DERIVED

• Kozuki N, Katz J, Englund JA, Steinhoff MC, Khatry SK, Shrestha L, Kuypers J, Mullany LC, Chu HY, LeClerq SC, Tielsch JM. Impact of maternal vaccination timing and influenza virus circulation on birth outcomes in rural Nepal. Int J Gynaecol Obstet. 2018 Jan;140(1):65-72. doi: 10.1002/ijgo.12341. Epub 2017 Nov 9.

  PMID: 28984909 DERIVED

• Steinhoff MC, Katz J, Englund JA, Khatry SK, Shrestha L, Kuypers J, Stewart L, Mullany LC, Chu HY, LeClerq SC, Kozuki N, McNeal M, Reedy AM, Tielsch JM. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial. Lancet Infect Dis. 2017 Sep;17(9):981-989. doi: 10.1016/S1473-3099(17)30252-9. Epub 2017 May 15.

  PMID: 28522338 DERIVED

• Tielsch JM, Steinhoff M, Katz J, Englund JA, Kuypers J, Khatry SK, Shrestha L, LeClerq SC. Designs of two randomized, community-based trials to assess the impact of influenza immunization during pregnancy on respiratory illness among pregnant women and their infants and reproductive outcomes in rural Nepal. BMC Pregnancy Childbirth. 2015 Feb 20;15:40. doi: 10.1186/s12884-015-0470-y.

  PMID: 25879974 DERIVED

MeSH Terms

Conditions

Influenza, Human; Whooping Cough; Hepatitis E

Interventions

Influenza Vaccines; vaxigrip; Sodium Chloride

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Mark C Steinhoff, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2009
• First Posted: December 17, 2009
• Study Start: November 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: October 1, 2017
• Last Updated: February 1, 2022

Record last verified: 2022-01

Locations

NE (1)