The Safety of Boostrix Following Routine Immunization of Pregnant Women

NCT03463577 | Completed Results

• 1 other identifier: 207221
• Study Type: observational
• Target: 65,783
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to assess the safety of Boostrix administered on or after the first day of the 27th week of pregnancy by conducting a post-marketing study that provided safety information to the public and healthcare providers. This was one of the largest cohorts of pregnant women vaccinated with Boostrix in the U.S. Through partnership between Kaiser Permanente Southern California (KPSC) and the sponsor, GlaxoSmithKline (GSK), information about the safety of maternal vaccination with Boostrix and maternal and infant adverse events (AEs) in a community setting was gained.

Conditions

Whooping Cough

Keywords

whooping cough, Boostrix, Tdap, safety, pregnancy, infants

Outcome Measures

Primary Outcomes (3)

• Incidence Rate (Per 1000 Person-years) of Pre-specified Maternal Adverse Events for Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort-women Groups

  The incidence rate (per 1000) of maternal adverse events was calculated as the total number of adverse events in the numerator and the total person-years at risk in the denominator. Every unexposed woman was assigned an index date that is determined by the number of days from pregnancy start to the Boostrix vaccination date of her matched exposed woman. The same number of days calculated in the exposed woman was added to the pregnancy start of the unexposed woman to identify her index date. The pre-specified maternal adverse events assessed were pre-eclampsia and eclampsia; Intra-uterine infections.

  From date of Boostrix vaccination (Exposed cohort women-on or after 1st day of 27th week of pregnancy) or from an index date (Unexposed historical cohort women) until end of enrollment or pregnancy, whichever came first, up to 13 weeks

• Incidence Rate (Per 1000 Persons) of Prespecified Maternal Adverse Events for Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Women Groups

  Incidence rate (per 1000) consisted of the total number of adverse events in the numerator and the number of persons at risk in the denominator. Every unexposed woman was assigned an index date that is determined by the number of days from pregnancy start to the Boostrix vaccination date of her matched exposed woman. The same number of days calculated in the exposed woman was added to the pregnancy start of the unexposed woman to identify her index date. The pre-specified maternal adverse event assessed was preterm delivery.

  From date of Boostrix vaccination (Exposed cohort women-on or after 1st day of 27th week of pregnancy) or from an index date (Unexposed historical cohort women) until end of enrollment or pregnancy, whichever came first, up to 13 weeks

• Incidence Rate (Per 1000 Persons) of Pre-specified Infant Adverse Events for Exposed Cohort infants-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Infants Groups

  The incidence rate (per 1000) of adverse events was calculated as the total number of adverse events in the numerator and the total of persons at risk in the denominator. The pre-specified infant adverse event assessed was small for gestational age.

  From birth through 6 months of age

Secondary Outcomes (6)

• Incidence Rate (Per 1000 Person-years) of Other Maternal Adverse Events for Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Women Groups

  From date of Boostrix vaccination (Exposed cohort women-on or after 1st day of 27th week of pregnancy) or from an index date (Unexposed historical cohort women) until end of enrollment or pregnancy, whichever came first, up to 13 weeks

• Incidence Rate (Per 1000 Persons) of Other Maternal Adverse Events for Exposed Cohort women-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Women Groups

  From date of Boostrix vaccination (Exposed cohort women-on or after 1st day of 27th week of pregnancy) or from an index date (Unexposed historical cohort women) until end of enrollment or pregnancy, whichever came first, up to 13 weeks

• Incidence Rate (Per 1000 Persons) of Other Infant Adverse Events for Exposed Cohort infants-on or After 1st Day of 27th Week of Pregnancy and Unexposed Historical Cohort Infants Groups

  From birth through 6 months of age

• Incidence Rate (Per 1000 Person-years) of Women Adverse Events for Exposed Cohort Women-before 1st Day of 27th Week of Pregnancy Group

  For the Exposed cohort women-before 1st day of 27th week of pregnancy: from date of Boostrix vaccination until end of enrollment or pregnancy, whichever came first, up to 40 weeks

• Incidence Rate (Per 1000 Persons) of Women Adverse Events Presented for Exposed Cohort Women-before 1st Day of 27th Week of Pregnancy Group

  For the Exposed cohort women-before 1st day of 27th week of pregnancy: from date of Boostrix vaccination until end of enrollment or pregnancy, whichever came first, up to 40 weeks

Study Arms (6)

Exposed cohort women-on or after 1st day of 27th week of pregnancy

This group consisted of pregnant women who received the Tdap vaccine (Boostrix) on or after the 1st day of the 27th week of pregnancy during the period January 1, 2018 to January 31, 2019 who were not vaccinated with any other Tdap vaccine at any other time during the pregnancy.

Other: Safety assessment following routine immunization with Boostrix

Unexposed historical cohort women

This group consisted of women matched to Exposed cohort women-on or after 1st day of 27th week of pregnancy group and pregnant at least one day during the historical period between January 1, 2012-December 31, 2014 and did not receive any Tdap vaccine during the pregnancy.

Other: Safety assessment following routine immunization with Boostrix

Exposed cohort women-before 1st day of 27th week of pregnancy

This group consisted of pregnant women who received the Tdap vaccine (Boostrix) before the 1st day of the 27th week of pregnancy during the period January 1, 2018-January 31, 2019 who were not vaccinated with any other Tdap vaccine at any other time during the pregnancy.

Other: Safety assessment following routine immunization with Boostrix

Exposed cohort infants-on or after 1st day of 27th week of pregnancy

This group consisted of infants whose mothers belong to Exposed cohort women-on or after 1st day of 27th week of pregnancy group.

Other: Safety assessment following routine immunization with Boostrix

Unexposed historical cohort infants

This group consisted of infants whose mothers belong to the Unexposed historical cohort women group.

Other: Safety assessment following routine immunization with Boostrix

Exposed cohort infants-before 1st day of 27th week of pregnancy

This group consisted of infants whose mothers belong to the Exposed cohort women-before 1st day of 27th week of pregnancy group.

Other: Safety assessment following routine immunization with Boostrix

Interventions

Safety assessment following routine immunization with Boostrix OTHER

Subject-level data was collected for pregnant women and their infants through the Electronic Health Records.

Exposed cohort infants-before 1st day of 27th week of pregnancy; Exposed cohort infants-on or after 1st day of 27th week of pregnancy; Exposed cohort women-before 1st day of 27th week of pregnancy; Exposed cohort women-on or after 1st day of 27th week of pregnancy; Unexposed historical cohort infants; Unexposed historical cohort women

Eligibility Criteria

• Gender Eligibility Details: Pregnant women with prenatal care and continuous membership (allowing up to a 31-day gap) at KPSC between the 1st day of the 27th week of pregnancy and the index (vaccination) date.
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women with prenatal care and continuous membership (allowing up to a 31-day gap) at KPSC between the 1st day of the 27th week of pregnancy and the index date

You may qualify if:

• Pregnant women with prenatal care and continuous membership (allowing up to a 31-day gap) at KPSC between the 1st day of the 27th week of pregnancy and the index (vaccination) date.
• Exposed cohort (from the 27th week of gestation): Pregnant women vaccinated with Boostrix on or after the 1st day of the 27th week of pregnancy; who were not vaccinated with any other Tdap vaccine at any other time during the pregnancy in scope of this study.
• Unexposed cohort: Women matched to the exposed cohort and pregnant sometime during the approximate estimated period between January 1, 2012-December 31, 2014 and did not receive any Tdap vaccine during the pregnancy in scope of this study.
• Live born
• Born in KPSC hospitals
• Note: Pregnant women vaccinated with Boostrix during pregnancy before the 27th week of gestation, with membership at the date of vaccination, and who were not vaccinated with any other Tdap vaccine at any other time during the pregnancy in scope of this study will be part of a descriptive analysis (secondary objective).

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Kaiser Permanente: collaborator

Study Sites (1)

GSK Investigational Site

Pasadena, California, 91101, United States

Location

Related Publications (1)

• Florea A, Sy LS, Ackerson BK, Qian L, Luo Y, Becerra-Culqui T, Lee GS, Tian Y, Zheng C, Bathala R, Tartof SY, Campora L, Ceregido MA, Kuznetsova A, Poirrier JE, Rosillon D, Valdes L, Cheuvart B, Mesaros N, Meyer N, Guignard A, Tseng HF. Investigating Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Congenital Anomalies. Infect Dis Ther. 2023 Feb;12(2):411-423. doi: 10.1007/s40121-022-00731-8. Epub 2022 Dec 15.

  PMID: 36520325 DERIVED

MeSH Terms

Conditions

Whooping Cough

Interventions

Boostrix

Condition Hierarchy (Ancestors)

Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Limitations and Caveats

Main limitation: difference in background rates and time periods for both cohorts. Other: confounding by indication possible for a less select historical unvaccinated population. The study wasn't designed to study safety of exposure before 27 weeks of gestation and was conducted in a prepaid health plan, so findings may not be generalized to uninsured populations. Congenital anomalies analysis performed by event code without adjustment for multiple testing.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2018
• First Posted: March 13, 2018
• Study Start: April 13, 2018
• Primary Completion: August 4, 2020
• Study Completion: August 4, 2020
• Last Updated: May 18, 2022
• Results First Posted: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)