Descriptive, Post-marketing, Passive Surveillance Safety Study of ADACEL™ Vaccine

NCT00258882 | Completed Results

• 1 other identifier: TD512
• Study Type: observational
• Target: 327,293
• Locations: 1 country
• Sites: 3

Brief Summary

To further characterize the vaccine safety profile and to identify any signals of potentially vaccine-related adverse events (AEs) not detected during pre-licensure studies.

Conditions

Pertussis

Keywords

Tetanus Toxoid,; acellular pertussis,; diphtheria toxoid

Outcome Measures

Primary Outcomes (6)

• Twenty One Pre-specified Outcomes of Interest as Obtained From International Coding of Diseases (ICD-9) Codes Captured After Adacel Vaccination in Clinical Database

  The twenty one pre-specified outcomes of special interest screened for in this study included: Arthritis, Arthralgia, or Arthropathy; Bell's Palsy; Diabetes; Encephalitis; Encephalopathy; Febrile Illness; Guillain-Barré; Hemolytic Anemia; Hypersensitivity; Idiopathic Thrombocytopenic Purpura (ITP); Lupus; Mixed Connective Tissue Disease; Multiple Sclerosis; Neuralgia; Neuritis; Neuropathy; Rheumatoid Arthritis; Scleroderma; Seizure; Severe Local Reaction; Transverse Myelitis. Comparison of events rates was performed using the risk-interval cohort design. In this design, the combined experience of individuals receiving Adacel vaccine served as their own control for evaluation of pre-specified outcomes of interest. Rates of events occurring during Days 0 to X (where X = 7, 14, 30, and 60) following vaccination were compared to rates of events occurring in the same individuals during Days 61 to 120 following vaccination.

  Days 0 to 60 and Day 61 to 120 following vaccination

• Twenty One Pre-specified Outcomes of Interest (ICD-9 Codes) Captured After Adacel Vaccination in Clinic Database

  The twenty one pre-specified outcomes of special interest screened for in this study included: Arthritis, Arthralgia, or Arthropathy; Bell's Palsy; Diabetes; Encephalitis; Encephalopathy; Febrile Illness; Guillain-Barré; Hemolytic Anemia; Hypersensitivity; ITP; Lupus; Mixed Connective Tissue Disease; Multiple Sclerosis; Neuralgia; Neuritis; Neuropathy; Rheumatoid Arthritis; Scleroderma; Seizure; Severe Local Reaction; Transverse Myelitis. Comparison of events rates was performed using the historic cohort design in which screening for possible new-onset chronic illnesses during the first 6 months following vaccination was performed. For each age-subgroup event, rates during the 6 months following vaccination among persons receiving Adacel vaccine were compared to event rates during the 6 months following vaccination among persons in the same age subgroup who received Td vaccine, but no live virus vaccine, during the year prior to initiation of this study.

  Days 0 up to 180 following vaccination

• All Diagnoses (Coded as ICD-9 Codes) Occurring During Specific Periods After Vaccination in All Adacel Exposed Individuals in Emergency Department and Hospital Databases.

  Surveillance for acute onset outcomes occurring shortly (days to weeks) after vaccination was performed using the risk-interval cohort design. In this design, the combined experience of individuals receiving Adacel vaccine served as their own control for evaluation of acute events. Rates of events occurring during Days 0 to X (where X = 7, 14, 30, and 60) following vaccination were compared to rates of events occurring in the same individuals during Days 61 to 120 following vaccination

  Days 0 to 60 and Day 61 to 120 following vaccination

• All Diagnoses (Coded as ICD-9 Codes) Occurring During 6 Months After Vaccination in All Adacel Exposed Individuals in Emergency Department and Hospital Databases.

  Comparison of events rates was performed using the historic cohort design in which screening for possible new-onset chronic illnesses during the first 6 months following vaccination was performed. For each age-subgroup event, rates during the 6 months following vaccination among persons receiving Adacel vaccine were compared to event rates during the 6 months following vaccination among persons in the same age subgroup who received Td vaccine, but no live virus vaccine, during the year prior to initiation of this study.

  Days 0 to 180 following vaccination

• Summary of Maternal Outcomes in Pregnant Adacel Recipients and Pregnant Non-Adacel Recipient Controls

  Pregnancies were identified by positive pregnancy tests or prenatal visits within 9 months prior to vaccination with no record of pre-vaccination delivery or abortion, or by prenatal visits, therapeutic abortions, or deliveries within 10 months after vaccination. For all such pregnancies, further review (including chart review, provider and vaccinee interviews, or other appropriate steps) was conducted to identify those for whom it could not be excluded that the individual was pregnant at the time of vaccination or within 28 days thereafter. Such pregnancies were reported by Kaiser Permanente Vaccine Study Center to the Adacel Pregnancy Registry. Maternal and fetal outcomes (up to 1 month of life) were enumerated. For each pregnant Adacel vaccine subjects, 3 age-matched non-Adacel vaccinated controls (± 1 year) that had a first positive pregnancy test during the same month (± 1 month). Rates of events of maternal and fetal outcomes were compared between the 2 groups.

  Pregnancy to Delivery, up to 9 months

• Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls.

  Pregnancies were identified by positive pregnancy tests or prenatal visits within 9 months prior to vaccination with no record of pre-vaccination delivery or abortion, or by prenatal visits, therapeutic abortions, or deliveries within 10 months after vaccination. For all such pregnancies, further review (including chart review, provider and vaccinee interviews, or other appropriate steps) was conducted to identify those for whom it could not be excluded that the individual was pregnant at the time of vaccination or within 28 days thereafter. Such pregnancies were reported by Kaiser Permanente Vaccine Study Center to the Adacel Pregnancy Registry. Maternal and fetal outcomes (up to 1 month of life) were enumerated. For each pregnant Adacel vaccine subjects, 3 age-matched non-Adacel vaccinated controls (± 1 year) that had a first positive pregnancy test during the same month (± 1 month). Rates of events of maternal and fetal outcomes were compared between the 2 groups.

  Pregnancy to Delivery, up to 9 months

Interventions

Tetanus Toxoid, acellular pertussis, diphtheria toxoid BIOLOGICAL

0.5 mL, Intramuscular

Also known as: Adacel®

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Passive surveillance by review of Kaiser Permanente Medical Care Program (KPMCP) computerized records and state mortality tapes

You may qualify if:

• Receipt of ADACEL vaccine during the study period

You may not qualify if:

• None

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (3)

Unknown Facility

Oakland, California, United States

Location

Unknown Facility

Aurora, Colorado, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Related Publications (1)

• Baxter R, Hansen J, Timbol J, Pool V, Greenberg DP, Johnson DR, Decker MD. Post-licensure safety surveillance study of routine use of tetanus toxoid, reduced diphtheria toxoid and 5-component acellular pertussis vaccine. Hum Vaccin Immunother. 2016 Nov;12(11):2742-2748. doi: 10.1080/21645515.2016.1201622. Epub 2016 Jul 7.

  PMID: 27388557 RESULT

MeSH Terms

Conditions

Whooping Cough; Tetanus

Interventions

Tetanus Toxoid; Diphtheria Toxoid; adacel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

As a result of screening using The Risk Interval and The Historic Cohort methods incident rates for 1030 outcomes were flagged as elevated. In post-hoc manual review no safety signals were identified. Details highlighted in the manuscript.

Results Point of Contact

• Title: Medical Drector
• Organization: Sanofi Pasteur Inc

RegistryContactus@sanofipasteur.com

Study Officials

• Medical Director

  Sanofi Pasteur Inc.

  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: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2005
• First Posted: November 28, 2005
• Study Start: January 1, 2006
• Primary Completion: July 1, 2011
• Study Completion: December 1, 2012
• Last Updated: July 17, 2018
• Results First Posted: April 13, 2016

Record last verified: 2018-06

Locations

US (3)