Fever After Simultaneous Versus Sequential Vaccination in Young Children

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03165981
• Collaborator: Centers for Disease Control and Prevention (U.S. Fed), Kaiser Permanente (Other)
• Enrollment: 221
• Locations: 3
• Arms: 2
• Actual Duration (Months): 4.7
• Patients Per Site: 73.7
• Patients Per Site Per Month: 15.7

Study Details

Study Description

Brief Summary

A prospective, randomized open-label clinical trial that will be conducted during the 2017-2018 influenza season. During the 2017-2018 season, approximately 280 children will be enrolled at Duke University Medical Center and Kaiser Permanente Northern California. Eligible children will be randomized to receive simultaneous or sequentially administered US licensed PCV13, US-licensed DTaP vaccine, and US-licensed inactivated influenza vaccine (IIV). Children in the simultaneous group will receive PCV13, DTaP, and IIV vaccines at Visit 1, and then return for a health education visit without vaccination about 2 weeks later (Visit 2). Children in the sequential group will receive both PCV13 and DTaP without IIV at Visit 1, and then will receive IIV and health education about 2 weeks later (Visit 2). Parents will record the occurrence of fever, solicited adverse events, medical care utilization, and receipt of antipyretics over 8 days following Visit 1 and Visit 2. In addition, febrile seizures and serious adverse events will be recorded for the entire study period (from enrollment through 8 days following the Visit 2) as determined through parental report and chart review. Parental perceptions about their child's vaccine schedule will be assessed on the 8th day following Visit 2.

Condition or Disease	Intervention/Treatment	Phase
Fever After Vaccination; Fever; Febrile Seizure	Biological: PCV13; Biological: DTaP; Biological: IIV	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 221 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Prospective, Randomized, Open-label Clinical Trial to Assess Fever Following Simultaneous Versus Sequential Administration of PCV13, DTaP Vaccine and IIV in Young Children
• Actual Study Start Date: Aug 25, 2017
• Actual Primary Completion Date: Jan 15, 2018
• Actual Study Completion Date: Jan 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Simultaneous vaccination arm In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2.	Biological: PCV13; ACIP Recommended vaccine; Other Names: 13-valent Conjugate Pneumococcal Vaccine ; Biological: DTaP; ACIP Recommended vaccine; Other Names: Diphtheria, Tetanus, and Acellular Pertussis Vaccine ; Biological: IIV; ACIP Recommended vaccine; Other Names: Quadrivalent Inactivated Influenza Vaccine IIV4 Flu Vaccine
Other: Sequential vaccination arm In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2.	Biological: PCV13; ACIP Recommended vaccine; Other Names: 13-valent Conjugate Pneumococcal Vaccine ; Biological: DTaP; ACIP Recommended vaccine; Other Names: Diphtheria, Tetanus, and Acellular Pertussis Vaccine ; Biological: IIV; ACIP Recommended vaccine; Other Names: Quadrivalent Inactivated Influenza Vaccine IIV4 Flu Vaccine

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Fever Following Vaccination [2 days post administration]

   Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1 and/or Visit 2.

Secondary Outcome Measures

1. Number of Participants With Fever Visit 1 [2 days post administration]

   Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1

2. Number of Participants With Fever Visit 2 [2 days post administration]

   Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 2

3. Number of Participants With Grade 2 and/or 3 Following Visit 1 [2 days post administration]

   Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 1. (Moderate/severe fever: ≥ 38.6°C or ≥ 101.4°F)

4. Number of Participants With Grade 2 and/or 3 Following Visit 2 [2 days post administration]

   Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 2.

5. Number of Participants With Grade 2 and/or 3 Following Visit 1 and Visit 2 [2 days post administration]

   Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 1 and Visit 2 combined.

6. Duration of Fever - Visit 1 [8 days post administration]

   Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following Visit 1. Note: fever starting on day 1 or 2 could continue through day 8.

7. Duration of Fever - Visit 2 [8 days post administration]

   Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following Visit 2. Note: fever starting on day 1 or 2 could continue through day 8.

8. Duration of Fever - Visit 1 and 2 Combined [8 days post administration]

   Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following and Visit 1 and Visit 2 combined. Note: fever starting on day 1 or 2 could continue through day 8.

9. Number of Participants With Medical Care Utilization - Visit 1 [2 days post administration]

   Proportion of children with medical care utilization (telephone call, medical office visit, emergency department visit, or hospital admission) for fever on day 1 and/or day 2 following Visit 1.

10. Number of Participants With Medical Care Utilization - Visit 2 [2 days post administration]

    Proportion of children with medical care utilization (telephone call, medical office visit, emergency department visit, or hospital admission) for fever on day 1 and/or day 2 following Visit 2.

11. Number of Participants With Medical Care Utilization - Visit 1 and 2 Combined [2 days post administration]

    Proportion of children with medical care utilization (telephone call, medical office visit, emergency department visit, or hospital admission) for fever on day 1 and/or day 2 following Visit 1 and Visit 2 combined.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 16 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. 12 through 16 months of age (i.e. from the 1-year birthday until the day before 17 months of age) at the time of vaccination

2. Stable health as determined by investigator's clinical examination and assessment of child's medical history

3. Has received all immunizations recommended by Advisory Committee for Immunization Practices (ACIP) during the first year of life with the exception of rotavirus and influenza vaccines.

4. The parent(s)/ legally authorized representative(s) LAR(s) intend for the child to receive DTaP and PCV13 in addition to this season's IIV

5. The parent(s)/LAR(s) must be willing and capable of providing permission for their child to participate through the written informed consent process

6. The parent(s)/LAR(s) must be able to comply with the requirements of the protocol (e.g., completion of the memory aid (either electronic or paper diary), return for follow-up visits, respects intervals between the visits and have telephone access.

7. The parent(s)/LAR(s) must be English speaking

8. The parent(s)/LAR(s) must agree to sign a medical release for the child so that study personnel may obtain medical information about the child's health (if needed)

Exclusion Criteria:

1. History of any seizure (including febrile seizure) in the child or a febrile seizure in a first degree relative

2. Has already completed influenza vaccination during the current season per ACIP recommendations

3. Receipt of more than 3 previous doses of DTaP

4. Received the 3rd dose of DTaP within 6 months of Visit 1

5. Receipt of more than 3 previous doses of PCV13

6. Received the 3rd dose of PCV13 within 8 weeks of Visit 1

7. History of a severe allergic reaction (e.g. anaphylaxis) to a previous dose of any influenza, diphtheria toxoid-, tetanus toxoid-, or pertussis-containing vaccine, or pneumococcal vaccine.

8. History of a severe allergic reaction (e.g., anaphylaxis) to any component (including egg protein) of any of the three vaccines used in this study; or a latex allergy.

9. History of Guillain-Barré syndrome within 6 weeks following a prior dose of influenza, DTaP, or tetanus toxoid containing vaccine

10. History of a progressive neurologic disorder

11. History of encephalopathy within 7 days of a previous pertussis-containing vaccine

12. History of collapse within 3 days after a prior dose of DTaP

13. Received any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to Visit 1

14. Received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to Visit 1, or expects to receive an experimental/investigational agent during the study period (up to 8 days after visit

1. A moderate to severe acute illness within 72 hours of Visit 1

2. A reported temperature greater than or equal to 100.4°F (38.0°C) within 72 hours prior enrollment or a temperature (measured by temporal artery thermometer) greater than or equal to 100.4°F (38.0°C) at the time of enrollment

3. Receipt of an antipyretic medication (acetaminophen or ibuprofen) within 24 hours prior to enrollment

4. Parent(s)/LAR is planning to administer a prophylactic antipyretic or medication on the day of, and/or within 7 days following Visit 1 or Visit 2

5. Long term (at least 14 consecutive days) oral corticosteroids (prednisone 2 mg/kg/day or equivalent other glucocorticoid), any parenteral steroids, high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) or other immune-modifying drugs or immunosuppressants within the preceding 6 months prior to Visit 1

6. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and or their provider's routine physical examination

7. Has an active neoplastic disease, a history of any hematologic malignancy, current bleeding disorder, or taking anticoagulants.

8. Unable to receive an intramuscular injection in the thigh

9. Any condition deemed by the investigator to place the child at increased risk as a result of their participation in the study

10. Any child or grandchild of a study investigator or study team member

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente Northern California	Oakland	California	United States	94612
2	Centers for Disease Control and Prevention	Atlanta	Georgia	United States	30333
3	Duke University	Durham	North Carolina	United States	27705

Sponsors and Collaborators

• Duke University
• Centers for Disease Control and Prevention
• Kaiser Permanente

Investigators

• Principal Investigator: Emmanuel B Walter, MD, MPH, Duke University
• Principal Investigator: Karen Broder, MD, Centers for Disease Control and Prevention
• Principal Investigator: Nicola Klein, MD, PhD, Kaiser Permanente

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 2, 2018

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03165981
• Other Study ID Numbers: Pro00082484; 200 2012 53663 0009
• First Posted: May 24, 2017
• Last Update Posted: Feb 8, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Duke University: Influenza vaccine; fever following vaccination; PCV13 vaccine; DTaP vaccine; pneumococcal vaccine
• Additional relevant MeSH terms: Seizures; Seizures, Febrile; Fever; Hyperthermia; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Period Title: Overall Study
STARTED	110	111
Per Protocol Population	99	107
COMPLETED	99	107
NOT COMPLETED	11	4

Baseline Characteristics

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm	Total
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	Total of all reporting groups
Overall Participants	99	107	206
Age (Months) [Median (Full Range) ]
Median (Full Range) [Months]	14.1	14.8	14.7
Sex: Female, Male (Count of Participants)
Female	48 48.5%	55 51.4%	103 50%
Male	51 51.5%	52 48.6%	103 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	21 21.2%	22 20.6%	43 20.9%
Not Hispanic or Latino	78 78.8%	85 79.4%	163 79.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	7 7.1%	9 8.4%	16 7.8%
Asian	6 6.1%	11 10.3%	17 8.3%
Native Hawaiian or Other Pacific Islander	0 0%	2 1.9%	2 1%
Black or African American	10 10.1%	6 5.6%	16 7.8%
White	52 52.5%	57 53.3%	109 52.9%
More than one race	18 18.2%	19 17.8%	37 18%
Unknown or Not Reported	6 6.1%	3 2.8%	9 4.4%
Region of Enrollment (participants) [Number]
United States	99 100%	107 100%	206 100%
Insurance (Count of Participants)
Any Private	63 63.6%	84 78.5%	147 71.4%
Public	18 18.2%	10 9.3%	28 13.6%
None	18 18.2%	13 12.1%	31 15%
Number of Children Living in Home (Children) [Median (Full Range) ]
Median (Full Range) [Children]	2	2	2
Day Care (Count of Participants)
Full-time (4-5 days/weeks)	22 22.2%	34 31.8%	56 27.2%
Part-time (3 or less/weeks)	17 17.2%	16 15%	33 16%
None	60 60.6%	57 53.3%	117 56.8%
Gestational Age in Weeks (Weeks) [Median (Full Range) ]
Median (Full Range) [Weeks]	39	39	39
Birth Weight in Pounds (Pounds) [Median (Full Range) ]
Median (Full Range) [Pounds]	7.25	7.13	7.13
Receipt of 1st or Only Dose of Influenza Vaccine for the Season (Count of Participants)
Count of Participants [Participants]	90 90.9%	102 95.3%	192 93.2%
Receipt of 2nd Dose of Influenza Vaccine for the Season (Count of Participants)
Count of Participants [Participants]	9 9.1%	5 4.7%	14 6.8%
Receipt of Concomitant Vaccine (Count of Participants)
Count of Participants [Participants]	87 87.9%	98 91.6%	185 89.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Fever Following Vaccination
Description	Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1 and/or Visit 2.
Time Frame	2 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Count of Participants [Participants]	8 8.1%	10 9.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simultaneous Vaccination Arm, Sequential Vaccination Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7588
	Comments
	Method	Mantel Haenszel
	Comments	Mantel Haenzel is stratified by site.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.36 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	RR is adjusted by site.

2. Secondary Outcome

Title	Number of Participants With Fever Visit 1
Description	Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 1
Time Frame	2 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Count of Participants [Participants]	8 8.1%	9 8.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simultaneous Vaccination Arm, Sequential Vaccination Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.9412
	Comments
	Method	Mantel Haenszel
	Comments	Mantel Haenzel is stratified by site.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.39 to 2.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	RR is adjusted by site.

3. Secondary Outcome

Title	Number of Participants With Fever Visit 2
Description	Proportion of children with fever (temperature ≥ 38.0°C or ≥ 100.4°F) on day 1 and/or day 2 following Visit 2
Time Frame	2 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Count of Participants [Participants]	0 0%	1 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simultaneous Vaccination Arm, Sequential Vaccination Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3408
	Comments
	Method	Mantel Haenszel
	Comments	Mantel Haenzel is stratified by site.

4. Secondary Outcome

Title	Number of Participants With Grade 2 and/or 3 Following Visit 1
Description	Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 1. (Moderate/severe fever: ≥ 38.6°C or ≥ 101.4°F)
Time Frame	2 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Count of Participants [Participants]	4 4%	5 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simultaneous Vaccination Arm, Sequential Vaccination Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8325
	Comments
	Method	Mantel Haenszel
	Comments	Mantel Haenzel is stratified by site.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.24 to 3.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	RR is adjusted by site.

5. Secondary Outcome

Title	Number of Participants With Grade 2 and/or 3 Following Visit 2
Description	Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 2.
Time Frame	2 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Count of Participants [Participants]	0 0%	1 0.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simultaneous Vaccination Arm, Sequential Vaccination Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3408
	Comments
	Method	Mantel Haenszel
	Comments	Mantel Haenzel is stratified by site.

6. Secondary Outcome

Title	Number of Participants With Grade 2 and/or 3 Following Visit 1 and Visit 2
Description	Proportions of children with moderate/severe fever (Grade 2 and/or 3) on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
Time Frame	2 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Count of Participants [Participants]	4 4%	6 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simultaneous Vaccination Arm, Sequential Vaccination Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6101
	Comments
	Method	Mantel Haenszel
	Comments	Mantel Haenzel is stratified by site.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.21 to 2.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	RR is adjusted by site.

7. Secondary Outcome

Title	Duration of Fever - Visit 1
Description	Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following Visit 1. Note: fever starting on day 1 or 2 could continue through day 8.
Time Frame	8 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Mean (Full Range) [Fever Days]	1.3	1.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simultaneous Vaccination Arm, Sequential Vaccination Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.848
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Duration of Fever - Visit 2
Description	Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following Visit 2. Note: fever starting on day 1 or 2 could continue through day 8.
Time Frame	8 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Mean (Full Range) [Fever Days]	0	3

9. Secondary Outcome

Title	Duration of Fever - Visit 1 and 2 Combined
Description	Average number of consecutive days of fever (temperature ≥ 38.0°C or ≥ 100.4°F) per subject for fever starting on day 1 or 2 following and Visit 1 and Visit 2 combined. Note: fever starting on day 1 or 2 could continue through day 8.
Time Frame	8 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Mean (Full Range) [Fever Days]	1.3	1.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Simultaneous Vaccination Arm, Sequential Vaccination Arm
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Number of Participants With Medical Care Utilization - Visit 1
Description	Proportion of children with medical care utilization (telephone call, medical office visit, emergency department visit, or hospital admission) for fever on day 1 and/or day 2 following Visit 1.
Time Frame	2 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Count of Participants [Participants]	0 0%	0 0%

11. Secondary Outcome

Title	Number of Participants With Medical Care Utilization - Visit 2
Description	Proportion of children with medical care utilization (telephone call, medical office visit, emergency department visit, or hospital admission) for fever on day 1 and/or day 2 following Visit 2.
Time Frame	2 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Count of Participants [Participants]	0 0%	0 0%

12. Secondary Outcome

Title	Number of Participants With Medical Care Utilization - Visit 1 and 2 Combined
Description	Proportion of children with medical care utilization (telephone call, medical office visit, emergency department visit, or hospital admission) for fever on day 1 and/or day 2 following Visit 1 and Visit 2 combined.
Time Frame	2 days post administration

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Simultaneous Vaccination Arm	Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine	In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
Measure Participants	99	107
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	Adverse events were collected through 8 days post Visit 2.
Adverse Event Reporting Description	All-cause mortality, serious adverse events, and other AEs exceeding a frequency threshold of 1% (febrile seizure only) were collected and reported. Per protocol, the only AE collected was febrile seizure.
Arm/Group Title	Simultaneous Vaccination Arm		Sequential Vaccination Arm
Arm/Group Description	In the study arm, subjects will receive PCV13, DTaP and IIV vaccines during visit 1. Approximately 2 weeks later, subjects will receive a health education visit without vaccination during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine		In the study arm, subjects will receive PCV13 and DTaP during study visit 1. Approximately 2 weeks later, subjects will receive the IIV vaccine during study visit 2. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine IIV: ACIP Recommended vaccine
All Cause Mortality
	Simultaneous Vaccination Arm		Sequential Vaccination Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/99 (0%)		0/107 (0%)
Serious Adverse Events
	Simultaneous Vaccination Arm		Sequential Vaccination Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/99 (0%)		1/107 (0.9%)
General disorders
Dehydration	0/99 (0%)	0	1/107 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Simultaneous Vaccination Arm		Sequential Vaccination Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/99 (0%)		0/107 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.