36-Month Post-marketing Surveillance and Analysis of Menactra Vaccine in 2-10 Year Olds

• ClinicalTrials.gov Identifier: NCT00728260
• Recruitment Status: Completed
• First Posted: August 5, 2008
• Results First Posted: February 12, 2015
• Last Update Posted: February 12, 2015
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

• Study Type: Observational
• Study Design: Observational Model: Cohort
• Conditions: Meningitis; Meningococcal Disease
• Intervention: Biological: None administered in this study
• Enrollment: 1421

Participant Flow

Recruitment Details	Study participant accrual occurred from 18 October 2007 through 17 October 2010. Kaiser Permanente databases were reviewed for this study.
Pre-assignment Details	Medical utilization databases were reviewed for children 2 through 10 years of age receiving Menactra vaccine within Kaiser Permanente to identify the following medical care events during the 6 months after Menactra vaccination: all outcomes from hospitalizations and emergency department visits and selected outcomes from clinic visits.

Arm/Group Title	Menactra Vaccine Recipients
Arm/Group Description	Children 2 years through 10 years of age who received Menactra vaccine within Kaiser Permanente during the study period. They served as their own controls for evaluation of acute (Days 0-30) events. Rates of events occurring during Days 0-30 following vaccination were compared to rates of events occurring during Days 31-60 following vaccination. Six-month surveillance: For each individual receiving Menactra vaccine, the rate of an event in the 30-day follow-up period was compared with the rate of the same event in the 31-180-day follow-up period using age, sex, and seasonality as covariates in Cox regression analyses. Menactra vaccine was administered according to routine clinical practice.
Period Title: Overall Study
Started	1421
Completed	1421
Not Completed	0

Baseline Characteristics

Arm/Group Title		Menactra Vaccine Recipients
Arm/Group Description		Children 2 years through 10 years of age who received Menactra vaccine within Kaiser Permanente during the study period. They served as their own controls for evaluation of acute (Days 0-30) events. Rates of events occurring during Days 0-30 following vaccination were compared to rates of events occurring during Days 31-60 following vaccination. Six-month surveillance: For each individual receiving Menactra vaccine, the rate of an event in the 30-day follow-up period was compared with the rate of the same event in the 31-180-day follow-up period using age, sex, and seasonality as covariates in Cox regression analyses. Menactra vaccine was administered according to routine clinical practice.
Overall Number of Baseline Participants		1421
Baseline Analysis Population Description		Children 2 through 10 years of age who received Menactra vaccine within Kaiser Permanente during the study period.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1421 participants
	<=18 years	1421 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1421 participants
		8.36 (2.55)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1421 participants
	Female	709 49.9%
	Male	712 50.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	1421 participants
		1421
Seasonality [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1421 participants
December - February		163
March - May		372
June - August		593
September - November		294
		[1] Measure Description: Data represent participants receiving vaccine during each time period shown. One participant had received more than one dose of Menactra vaccine; each dose is counted in the seasonality section.
Indication for Vaccination [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1421 participants
Asplenia (Surgical or Congenital)		17
Complement Deficiency		2
Hereditary Elliptocytosis		1
Hereditary Spherocytosis		8
Sickle Cell Disease		44
Thalassemias		22
Other Hemoglobinopathy		9
Human Immunodeficiency Virus Infection		1
Travel-Related		364
Not Available		987
		[1] Measure Description: Based on automated subject data. Participants may be included in more than 1 category

Outcome Measures

1. Primary Outcome

Title	Summary of Diagnoses With Elevated Findings for Risk-Window vs. Control-Window Comparisons at the 5% Significance Level.
Description	Incidence rates for each diagnosis were calculated as the number of events divided by person-time and expressed as events per 1,000 person-months in each comparison window. Clinical setting is given in parenthesis as (H) for hospital.
Time Frame	Day 0 up to Day 30 post-vaccination

Outcome Measure Data

Analysis Population Description

All persons who received Menactra vaccine during the study period were included in the analysis.

Arm/Group Title	Menactra Vaccine Recipients
Arm/Group Description:	Children 2 years through 10 years of age who received Menactra vaccine within Kaiser Permanente during the study period. They served as their own controls for evaluation of acute (Days 0-30) events. Rates of events occurring during Days 0-30 following vaccination were compared to rates of events occurring during Days 31-60 following vaccination. Six-month surveillance: For each individual receiving Menactra vaccine, the rate of an event in the 30-day follow-up period was compared with the rate of the same event in the 31-180-day follow-up period using age, sex, and seasonality as covariates in Cox regression analyses. Menactra vaccine was administered according to routine clinical practice.
Overall Number of Participants Analyzed	1421
Measure Type: Number; Unit of Measure: Events per 1,000 person-months
Cellulitis and abscess (All ages combined; H)	1.4
Cellulitis and abscess (Subj.10 Yrs Old; H; n=870)	2.3

2. Primary Outcome

Title	Summary of Diagnoses With Elevated Findings for Risk-Window vs. Control-Window Comparisons at the 5% Significance Level.
Description	Incidence rates for each diagnosis were calculated as the number of events divided by person-time and expressed as events per 1,000 person-months in each comparison window. Clinical setting is given in parenthesis as (H) for hospital.
Time Frame	Day 31 up to Day 180 post-vaccination

Outcome Measure Data

Analysis Population Description

All persons who received Menactra vaccine during the study period were included in the analysis.

Arm/Group Title	Menactra Vaccine Recipients
Arm/Group Description:	Children 2 years through 10 years of age who received Menactra vaccine within Kaiser Permanente during the study period. They served as their own controls for evaluation of acute (Days 0-30) events. Rates of events occurring during Days 0-30 following vaccination were compared to rates of events occurring during Days 31-60 following vaccination. Six-month surveillance: For each individual receiving Menactra vaccine, the rate of an event in the 30-day follow-up period was compared with the rate of the same event in the 31-180-day follow-up period using age, sex, and seasonality as covariates in Cox regression analyses. Menactra vaccine was administered according to routine clinical practice.
Overall Number of Participants Analyzed	1421
Measure Type: Number; Unit of Measure: Events per 1,000 person-months
Cellulitis and abscess (All ages combined; H)	0.0
Cellulitis and abscess (Subj.10 Yrs Old; H; n=870)	0.0

3. Other Pre-specified Outcome

Title	Rates of Serious Adverse Events Per 1000 Doses at During 6 Months After Menactra Vaccination From Inpatient Database - All Ages Combined
Description	Only persons who received Menactra vaccine during the study period were surveyed and included in this outcome.
Time Frame	Day 0 up to 6 months post-vaccination

Outcome Measure Data

Analysis Population Description

Only persons who received Menactra vaccine during the study period were included in the analysis.

Arm/Group Title	Menactra Vaccine Recipients
Arm/Group Description:	Children 2 years through 10 years of age who received Menactra vaccine within Kaiser Permanente during the study period. They served as their own controls for evaluation of acute (Days 0-30) events. Rates of events occurring during Days 0-30 following vaccination were compared to rates of events occurring during Days 31-60 following vaccination. Six-month surveillance: For each individual receiving Menactra vaccine, the rate of an event in the 30-day follow-up period was compared with the rate of the same event in the 31-180-day follow-up period using age, sex, and seasonality as covariates in Cox regression analyses. Menactra vaccine was administered according to routine clinical practice.
Overall Number of Participants Analyzed	1421
Measure Type: Number; Unit of Measure: Events per 1,000 doses
Abdominal pain	0.70
Aspergillosis	0.70
Asthma	0.70
Cellulitis and abscess	1.41
Cerebral palsy	0.70
Congenital anomaly of ureter	0.70
Congenital atresia	0.70
Digestive congenital anomalies	070
Febrile illness	2.81
Feeding problem	0.70
Hereditary spherocytosis	0.70
Hydronephrosis	0.70
Malignant neoplasm	5.63
Other non-traumatic joint disorders	0.70
Pneumonia	0.70
Psychiatric	0.70
Pyogenic arthritis	0.70
Respiratory infection, upper	0.70
Sickle cell anemia	5.63
Small bowel obstruction	0.70
Trauma	2.11

Adverse Events

Time Frame	Surveillance period for serious adverse events was from the day of vaccination up to 6 months post-vaccination from the inpatient database.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Menactra Vaccine Recipients
Arm/Group Description	Children 2 years through 10 years of age who received Menactra vaccine within Kaiser Permanente during the study period. They served as their own controls for evaluation of acute (Days 0-30) events. Rates of events occurring during Days 0-30 following vaccination were compared to rates of events occurring during Days 31-60 following vaccination. Six-month surveillance: For each individual receiving Menactra vaccine, the rate of an event in the 30-day follow-up period was compared with the rate of the same event in the 31-180-day follow-up period using age, sex, and seasonality as covariates in Cox regression analyses. Menactra vaccine was administered according to routine clinical practice.
All-Cause Mortality
	Menactra Vaccine Recipients
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Menactra Vaccine Recipients
	Affected / at Risk (%)
Total	16/1421 (1.13%)
Congenital, familial and genetic disorders
Congenital Anomaly of ureter * 1	1/1421 (0.07%)
Sickle Cell Anemia * 1	8/1421 (0.56%)
Digestive congenital anomalies * 1	1/1421 (0.07%)
Congenital atresia * 1	1/1421 (0.07%)
Cerebral palsy * 1	1/1421 (0.07%)
Hereditary spherocytosis * 1	1/1421 (0.07%)
Gastrointestinal disorders
Abdominal Pain * 1	1/1421 (0.07%)
Small bowel obstruction * 1	1/1421 (0.07%)
General disorders
Febrile Illness * 1	4/1421 (0.28%)
Infections and infestations
Aspergillosis * 1	1/1421 (0.07%)
Pyogenic arthritis * 1	1/1421 (0.07%)
Respiratory infection, upper * 1	1/1421 (0.07%)
Cellulitis and abscess * 1	2/1421 (0.14%)
Pneumonia * 1	1/1421 (0.07%)
Injury, poisoning and procedural complications
Trauma * 1	3/1421 (0.21%)
Metabolism and nutrition disorders
Feeding problem * 1	1/1421 (0.07%)
Musculoskeletal and connective tissue disorders
Other non-traumatic joint disorders * 1	1/1421 (0.07%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm * 1	8/1421 (0.56%)
Psychiatric disorders
Psychiatric * 1	1/1421 (0.07%)
Renal and urinary disorders
Hydronephrosis * 1	1/1421 (0.07%)
Respiratory, thoracic and mediastinal disorders
Asthma * 1	1/1421 (0.07%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 16.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5.0%
	Menactra Vaccine Recipients
	Affected / at Risk (%)
Total	0/1421 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Drector
• Organization: Sanofi Pasteur Inc
• EMail: RegistryContactus@sanofipasteur.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hansen J, Zhang L, Eaton A, Baxter R, Robertson CA, Decker MD, Greenberg DP, Bassily E, Klein NP. Post-licensure safety surveillance study of routine use of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MenACWY-D) in infants and children. Vaccine. 2018 Apr 12;36(16):2133-2138. doi: 10.1016/j.vaccine.2018.02.107. Epub 2018 Mar 14.

• Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT00728260
• Other Study ID Numbers: MTA38
• First Submitted: May 7, 2008
• First Posted: August 5, 2008
• Results First Submitted: January 7, 2015
• Results First Posted: February 12, 2015
• Last Update Posted: February 12, 2015