Trial Outcomes & Findings for Descriptive, Post-marketing, Passive Surveillance Safety Study of ADACEL™ Vaccine (NCT NCT00258882)

Last Updated: 2018-07-17

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

327293 participants

Primary outcome timeframe

Days 0 to 60 and Day 61 to 120 following vaccination

Results posted on

2018-07-17

Participant Flow

Study participant accrual occurred from 02 September 2005 through 16 October 2006 using 3 Kaiser Permanente databases.

Databases were reviewed to identify persons who received Adacel vaccine and Td vaccinated historical controls. Two statistical analysis methods were used, risk interval and historic cohort method. Adacel-exposed pregnancy cases were matched to non-exposed pregnant controls (3:1 ratio).

Participant milestones

Participant milestones
Measure	Adacel Vaccine Group Participants who received Adacel vaccine during the study period were sub-grouped as 1) pregnant at the time of vaccination or who became pregnant within 28 days after vaccination and 2) non-pregnant recipients classified by age at vaccination.	Control Groups For each pregnant individual receiving Adacel vaccine, 3 control individuals not given Adacel vaccine were matched on age and month of their first positive pregnancy test. For non-pregnant individuals, age-matched individuals were identified who received Td vaccine but no live virus vaccine during the year prior to initiation of the study during the same month as Adacel vaccine recipient, but 1 year earlier.
Adacel Recipients Historic Cohort Method STARTED	124139	203154
Adacel Recipients Historic Cohort Method COMPLETED	124139	203154
Adacel Recipients Historic Cohort Method NOT COMPLETED	0	0
Adacel Recipients-Risk Interval Method STARTED	124139	0
Adacel Recipients-Risk Interval Method COMPLETED	124139	0
Adacel Recipients-Risk Interval Method NOT COMPLETED	0	0
Pregnancy Surveillance STARTED	225	675
Pregnancy Surveillance COMPLETED	225	675
Pregnancy Surveillance NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adacel Vaccine Group n=124139 Participants Participants who received Adacel vaccine during the study period were sub-grouped as 1) pregnant at the time of vaccination or who became pregnant within 28 days after vaccination and 2) non-pregnant recipients classified by age at vaccination. Each non-pregnant recipient served as their own control for evaluation of acute events. Rates of events occurring during Day 0 to 60 following vaccination were compared to rates of events occurring during Day 61 to 120 following vaccination (Short-term surveillance)	Control Groups n=203154 Participants Non-pregnant individuals matched by age to individuals who received Td vaccine but no live virus vaccine during the year prior to initiation of the study during the same month as Adacel vaccine recipient, but 1 year earlier.	Total n=327293 Participants Total of all reporting groups
Age, Categorical <=18 years	50214 Participants n=5 Participants	58823 Participants n=7 Participants	109037 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	70861 Participants n=5 Participants	119390 Participants n=7 Participants	190251 Participants n=5 Participants
Age, Categorical >=65 years	3064 Participants n=5 Participants	24941 Participants n=7 Participants	28005 Participants n=5 Participants
Age, Continuous	32.1 Years STANDARD_DEVIATION 19.0 • n=5 Participants	39.0 Years STANDARD_DEVIATION 21.6 • n=7 Participants	36.4 Years STANDARD_DEVIATION 20.9 • n=5 Participants
Sex: Female, Male Female	67067 Participants n=5 Participants	104898 Participants n=7 Participants	171965 Participants n=5 Participants
Sex: Female, Male Male	57072 Participants n=5 Participants	98256 Participants n=7 Participants	155328 Participants n=5 Participants
Region of Enrollment United States	124139 participants n=5 Participants	203154 participants n=7 Participants	327293 participants n=5 Participants
Seasonality (Time of vaccination) December to February	20293 Participants n=5 Participants	42397 Participants n=7 Participants	62690 Participants n=5 Participants
Seasonality (Time of vaccination) March to May	35651 Participants n=5 Participants	51039 Participants n=7 Participants	86690 Participants n=5 Participants
Seasonality (Time of vaccination) June to August	49173 Participants n=5 Participants	62906 Participants n=7 Participants	112079 Participants n=5 Participants
Seasonality (Time of vaccination) September to November	19022 Participants n=5 Participants	46812 Participants n=7 Participants	65834 Participants n=5 Participants

PRIMARY outcome

Timeframe: Days 0 to 60 and Day 61 to 120 following vaccination

Population: Individuals receiving Adacel vaccine served as their own control for evaluation of acute events.

Outcome measures

Outcome measures
Measure	Adacel Vaccine Group n=124139 Participants Participants who received Adacel vaccine during the study period.	Control Groups Age matched participants who received Td vaccine but no live virus vaccine, during the year prior to initiation of study during the same month as the Adacel vaccine recipient, 1 year earlier.
Twenty One Pre-specified Outcomes of Interest as Obtained From International Coding of Diseases (ICD-9) Codes Captured After Adacel Vaccination in Clinical Database	0 Events Per 1000 Person-months	—

PRIMARY outcome

Timeframe: Days 0 up to 180 following vaccination

Population: Individuals receiving Adacel vaccine served as their own control for evaluation of acute events.

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.

Outcome measures

Outcome measures
Measure	Adacel Vaccine Group n=124139 Participants Participants who received Adacel vaccine during the study period.	Control Groups n=203154 Participants Age matched participants who received Td vaccine but no live virus vaccine, during the year prior to initiation of study during the same month as the Adacel vaccine recipient, 1 year earlier.
Twenty One Pre-specified Outcomes of Interest (ICD-9 Codes) Captured After Adacel Vaccination in Clinic Database	0 Events Per 1000 Person-months	0 Events Per 1000 Person-months

PRIMARY outcome

Timeframe: Days 0 to 60 and Day 61 to 120 following vaccination

Population: Individuals receiving Adacel vaccine served as their own control for evaluation of acute events.

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

Outcome measures

Outcome measures
Measure	Adacel Vaccine Group n=124139 Participants Participants who received Adacel vaccine during the study period.	Control Groups Age matched participants who received Td vaccine but no live virus vaccine, during the year prior to initiation of study during the same month as the Adacel vaccine recipient, 1 year earlier.
All Diagnoses (Coded as ICD-9 Codes) Occurring During Specific Periods After Vaccination in All Adacel Exposed Individuals in Emergency Department and Hospital Databases.	0 Events Per 1000 Person-months	—

PRIMARY outcome

Timeframe: Days 0 to 180 following vaccination

Population: Individuals receiving Adacel vaccine served as their own control for evaluation of acute events.

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.

Outcome measures

Outcome measures
Measure	Adacel Vaccine Group n=124139 Participants Participants who received Adacel vaccine during the study period.	Control Groups Age matched participants who received Td vaccine but no live virus vaccine, during the year prior to initiation of study during the same month as the Adacel vaccine recipient, 1 year earlier.
All Diagnoses (Coded as ICD-9 Codes) Occurring During 6 Months After Vaccination in All Adacel Exposed Individuals in Emergency Department and Hospital Databases.	0 Events per 1000 Person-months	—

PRIMARY outcome

Timeframe: Pregnancy to Delivery, up to 9 months

Population: All persons in the database searches as being vaccinated with Adacel vaccine during pregnancy or within 28 days prior to becoming pregnant and age-matched pregnant controls who did not receive Adacel vaccine.

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.

Outcome measures

Outcome measures
Measure	Adacel Vaccine Group n=225 Participants Participants who received Adacel vaccine during the study period.	Control Groups n=675 Participants Age matched participants who received Td vaccine but no live virus vaccine, during the year prior to initiation of study during the same month as the Adacel vaccine recipient, 1 year earlier.
Summary of Maternal Outcomes in Pregnant Adacel Recipients and Pregnant Non-Adacel Recipient Controls Life Birth	165 Participants	442 Participants
Summary of Maternal Outcomes in Pregnant Adacel Recipients and Pregnant Non-Adacel Recipient Controls Spontaneous abortion (<20 weeks gestation)	21 Participants	102 Participants
Summary of Maternal Outcomes in Pregnant Adacel Recipients and Pregnant Non-Adacel Recipient Controls Early fetal death (20-27 weeks gestation)	0 Participants	1 Participants
Summary of Maternal Outcomes in Pregnant Adacel Recipients and Pregnant Non-Adacel Recipient Controls Late fetal death (at least 28 weeks gestation)	1 Participants	0 Participants
Summary of Maternal Outcomes in Pregnant Adacel Recipients and Pregnant Non-Adacel Recipient Controls Ectopic pregnancy	1 Participants	5 Participants
Summary of Maternal Outcomes in Pregnant Adacel Recipients and Pregnant Non-Adacel Recipient Controls Elective abortion	33 Participants	105 Participants
Summary of Maternal Outcomes in Pregnant Adacel Recipients and Pregnant Non-Adacel Recipient Controls Lost to follow-up	4 Participants	20 Participants

PRIMARY outcome

Timeframe: Pregnancy to Delivery, up to 9 months

Outcome measures

Outcome measures
Measure	Adacel Vaccine Group n=225 Participants Participants who received Adacel vaccine during the study period.	Control Groups n=675 Participants Age matched participants who received Td vaccine but no live virus vaccine, during the year prior to initiation of study during the same month as the Adacel vaccine recipient, 1 year earlier.
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Hypospadias	2 Infants	0 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Other specified anomalies of skin	0 Infants	2 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Encephalocele	1 Infants	0 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Specified congenital anomalies of lacrimal passage	4 Infants	18 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Ventricular septal defect	1 Infants	2 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Stenosis of pulmonary valve, congenital	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Patent ductus arteriosus	2 Infants	6 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Agenesis, hypoplasia, and dysplasia of lung	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Cleft palate, unilateral, incomplete	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Cleft palate with cleft lip, unspecified	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Tongue tie	1 Infants	6 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Undescended testis	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Congenital chordee	0 Infants	2 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Other penile anomalies	0 Infants	2 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Other obstructive defects of renal pelvis and uret	1 Infants	0 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Metatarsus varus	1 Infants	0 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Polydactyly of fingers	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Polydactyly of toes	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Other congenital deformity of hip (joint)	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Vascular hamartomas	1 Infants	2 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Congenital pigmentary anomalies of skin	1 Infants	5 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Specified congenital anomalies of breast	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Down's syndrome	0 Infants	1 Infants
Summary of Fetal Outcomes in Infants Born to Adacel Exposed Pregnant Women and Infants Born to Non-Adacel Exposed Pregnant Controls. Congenital anomaly, unspecified	0 Infants	2 Infants

Adverse Events

Adacel Vaccine Group

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Adacel Vaccine Group n=124139 participants at risk Participants who received Adacel vaccine during the study period. They are sub-grouped as those pregnant at the time of vaccination with Adacel or who became pregnant within 28 days after vaccination and other recipients are classified by age at vaccination.
Nervous system disorders Bell Palsy	0.00% 2/124139 • Adverse events data surveillance period were only in Adacel vaccine recipients from the day of vaccination up to 6 months post-vaccination from the Outpatient, Emergency Room and Hospital databases. Total number reported for the serious adverse events are events that were deemed possibly associated with the Adacel vaccine in the Outpatient, Emergency Room and Hospital databases.
Musculoskeletal and connective tissue disorders Guillain-Barré syndrome	0.00% 1/124139 • Adverse events data surveillance period were only in Adacel vaccine recipients from the day of vaccination up to 6 months post-vaccination from the Outpatient, Emergency Room and Hospital databases. Total number reported for the serious adverse events are events that were deemed possibly associated with the Adacel vaccine in the Outpatient, Emergency Room and Hospital databases.
Nervous system disorders Epilepsy	0.00% 1/124139 • Adverse events data surveillance period were only in Adacel vaccine recipients from the day of vaccination up to 6 months post-vaccination from the Outpatient, Emergency Room and Hospital databases. Total number reported for the serious adverse events are events that were deemed possibly associated with the Adacel vaccine in the Outpatient, Emergency Room and Hospital databases.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 1/124139 • Adverse events data surveillance period were only in Adacel vaccine recipients from the day of vaccination up to 6 months post-vaccination from the Outpatient, Emergency Room and Hospital databases. Total number reported for the serious adverse events are events that were deemed possibly associated with the Adacel vaccine in the Outpatient, Emergency Room and Hospital databases.

Other adverse events

Adverse event data not reported

Additional Information

Medical Drector

Sanofi Pasteur Inc

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
Publication restrictions are in place

Restriction type: OTHER