Trial Outcomes & Findings for Effect of Age and Prior Immunity to Response to Seasonal Influenza Vaccines in Children (NCT NCT01246999)
NCT ID: NCT01246999
Last Updated: 2016-12-29
Results Overview
Nasal washes were collected on days 2, 4 and 7 after vaccination. Nasal swab specimens were tested for the presence of vaccine viruses by quantitative viral culture in MDCK cells at 33º C and by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) amplification. The limit of detection of vaccine viruses was 10\^0.6 tissue culture infectious doses (50%)/ml for virus culture and 10\^0.4 tissue culture infectious doses (50%)/ml for qRT-PCR.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
34 participants
Primary outcome timeframe
baseline to day 7
Results posted on
2016-12-29
Participant Flow
In the first year participants were randomly assigned to receive LAIV twice, TIV twice, LAIV followed by TIV or TIV followed by LAIV. In the second year, randomization was confined to 2 groups: LAIV twice or TIV followed by LAIV. 8/34 participants were in the two arms not included in the analysis.
Participant milestones
| Measure |
LAIV - LAIV
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
TIV - LAIV
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
LAIV - TIV
LAIV will be given intranasally followed by TIV intramuscularly
|
TIV - TIV
TIV will be given IM followed by TIV IM
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
11
|
4
|
2
|
17
|
|
Overall Study
COMPLETED
|
11
|
3
|
2
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
2
|
Reasons for withdrawal
| Measure |
LAIV - LAIV
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
TIV - LAIV
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
LAIV - TIV
LAIV will be given intranasally followed by TIV intramuscularly
|
TIV - TIV
TIV will be given IM followed by TIV IM
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
2
|
Baseline Characteristics
Effect of Age and Prior Immunity to Response to Seasonal Influenza Vaccines in Children
Baseline characteristics by cohort
| Measure |
Total
n=34 Participants
Total of all reporting groups
|
LAIV - LAIV
n=11 Participants
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
TIV - LAIV
n=4 Participants
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
TIV - TIV
n=17 Participants
TIV will be given followed by TIV 28 days later
|
LAIV - TIV
n=2 Participants
LAIV will be given followed by TIV 28 days later
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
34 Participants
n=21 Participants
|
11 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=21 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=21 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Gender
Female
|
16 Participants
n=21 Participants
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Gender
Male
|
18 Participants
n=21 Participants
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
34 participants
n=21 Participants
|
11 participants
n=5 Participants
|
4 participants
n=7 Participants
|
17 participants
n=5 Participants
|
2 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: baseline to day 7Population: Outcome for shedding of live vaccine in all participants who received a live vaccine
Nasal washes were collected on days 2, 4 and 7 after vaccination. Nasal swab specimens were tested for the presence of vaccine viruses by quantitative viral culture in MDCK cells at 33º C and by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) amplification. The limit of detection of vaccine viruses was 10\^0.6 tissue culture infectious doses (50%)/ml for virus culture and 10\^0.4 tissue culture infectious doses (50%)/ml for qRT-PCR.
Outcome measures
| Measure |
Trivalent Seasonal Live Attenuated Influenza Vaccine
n=11 Participants
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
Seasonal Influenza Vaccine (TIV-LAIV)
n=15 Participants
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
All First Dose Live Vaccine
n=13 Participants
All subjects who received LAIV as a first dose
|
TIV - TIV
TIV will be given IM followed by TIV IM
|
|---|---|---|---|---|
|
Number of Subjects Shedding Vaccine Virus of Each Subtype by PCR
shedding H1N1
|
1 participants
|
6 participants
|
9 participants
|
—
|
|
Number of Subjects Shedding Vaccine Virus of Each Subtype by PCR
shedding H3N2
|
1 participants
|
5 participants
|
9 participants
|
—
|
|
Number of Subjects Shedding Vaccine Virus of Each Subtype by PCR
shedding B
|
1 participants
|
10 participants
|
10 participants
|
—
|
SECONDARY outcome
Timeframe: days 2, 4 and 7After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Outcome measures
| Measure |
Trivalent Seasonal Live Attenuated Influenza Vaccine
n=11 Participants
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
Seasonal Influenza Vaccine (TIV-LAIV)
n=3 Participants
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
All First Dose Live Vaccine
n=2 Participants
All subjects who received LAIV as a first dose
|
TIV - TIV
n=15 Participants
TIV will be given IM followed by TIV IM
|
|---|---|---|---|---|
|
Mean Peak H1N1 Virus Titer, Dose 1
|
1.8 log10 TCID(50)/ml
Standard Deviation 1.7
|
0.0 log10 TCID(50)/ml
Standard Deviation 0.0
|
1.4 log10 TCID(50)/ml
Standard Deviation 1.9
|
0.0 log10 TCID(50)/ml
Standard Deviation 0000
|
SECONDARY outcome
Timeframe: days 2, 4 and 7After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Outcome measures
| Measure |
Trivalent Seasonal Live Attenuated Influenza Vaccine
n=11 Participants
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
Seasonal Influenza Vaccine (TIV-LAIV)
n=3 Participants
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
All First Dose Live Vaccine
n=2 Participants
All subjects who received LAIV as a first dose
|
TIV - TIV
n=15 Participants
TIV will be given IM followed by TIV IM
|
|---|---|---|---|---|
|
Mean Peak H3N2 Virus Titer, Dose 1
|
0.9 log10 TCID(50)/ml
Standard Deviation 1.6
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
SECONDARY outcome
Timeframe: days 2, 4 and 7After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Outcome measures
| Measure |
Trivalent Seasonal Live Attenuated Influenza Vaccine
n=11 Participants
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
Seasonal Influenza Vaccine (TIV-LAIV)
n=3 Participants
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
All First Dose Live Vaccine
n=2 Participants
All subjects who received LAIV as a first dose
|
TIV - TIV
n=15 Participants
TIV will be given IM followed by TIV IM
|
|---|---|---|---|---|
|
Mean Peak Influenza B Virus Titer, Dose 1
|
1.6 log10 TCID(50)/ml
Standard Deviation 2.0
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
2.1 log10 TCID(50)/ml
Standard Deviation 2.9
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
SECONDARY outcome
Timeframe: days 2, 4 and 7After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Outcome measures
| Measure |
Trivalent Seasonal Live Attenuated Influenza Vaccine
n=11 Participants
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
Seasonal Influenza Vaccine (TIV-LAIV)
n=3 Participants
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
All First Dose Live Vaccine
n=2 Participants
All subjects who received LAIV as a first dose
|
TIV - TIV
n=15 Participants
TIV will be given IM followed by TIV IM
|
|---|---|---|---|---|
|
Mean Peak H1N1 Virus Titer, Dose 2
|
0.3 log10 TCID(50)/ml
Standard Deviation 0.99
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
1 log10 TCID(50)/ml
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: days 2, 4 and 7After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Outcome measures
| Measure |
Trivalent Seasonal Live Attenuated Influenza Vaccine
n=11 Participants
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
Seasonal Influenza Vaccine (TIV-LAIV)
n=3 Participants
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
All First Dose Live Vaccine
n=2 Participants
All subjects who received LAIV as a first dose
|
TIV - TIV
n=15 Participants
TIV will be given IM followed by TIV IM
|
|---|---|---|---|---|
|
Mean Peak H3N2 Virus Titer, Dose 2
|
0.3 log10 TCID(50)/ml
Standard Deviation 0.9
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
0.3 log10 TCID(50)/ml
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: days 2, 4 and 7After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.
Outcome measures
| Measure |
Trivalent Seasonal Live Attenuated Influenza Vaccine
n=11 Participants
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
Seasonal Influenza Vaccine (TIV-LAIV)
n=3 Participants
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
All First Dose Live Vaccine
n=2 Participants
All subjects who received LAIV as a first dose
|
TIV - TIV
n=15 Participants
TIV will be given IM followed by TIV IM
|
|---|---|---|---|---|
|
Mean Peak Influenza B Virus Titer, Dose 2
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
0 log10 TCID(50)/ml
Standard Deviation 0
|
1.3 log10 TCID(50)/ml
Standard Deviation 2
|
Adverse Events
LAIV-LAIV
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
TIV-LAIV
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
LAIV-TIV
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
TIV-TIV
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LAIV-LAIV
n=11 participants at risk
LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later
Trivalent Seasonal Live attenuated Influenza vaccine: 0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days
|
TIV-LAIV
n=15 participants at risk
TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later
Seasonal Influenza Vaccine TIV/LAIV: TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later
|
LAIV-TIV
n=2 participants at risk
LAIV will be given intranasally followed by TIV intramuscularly
|
TIV-TIV
n=17 participants at risk
TIV will be given IM followed by IV IM
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
runny nose
|
27.3%
3/11
|
13.3%
2/15
|
0.00%
0/2
|
17.6%
3/17
|
|
General disorders
fever
|
0.00%
0/11
|
6.7%
1/15
|
0.00%
0/2
|
11.8%
2/17
|
|
General disorders
fatigue
|
27.3%
3/11
|
0.00%
0/15
|
50.0%
1/2
|
0.00%
0/17
|
|
General disorders
body ache
|
0.00%
0/11
|
0.00%
0/15
|
0.00%
0/2
|
11.8%
2/17
|
|
Nervous system disorders
headache
|
0.00%
0/11
|
0.00%
0/15
|
0.00%
0/2
|
5.9%
1/17
|
|
Eye disorders
eye redness
|
9.1%
1/11
|
6.7%
1/15
|
0.00%
0/2
|
0.00%
0/17
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
45.5%
5/11
|
13.3%
2/15
|
0.00%
0/2
|
29.4%
5/17
|
|
General disorders
nose bleed
|
0.00%
0/11
|
6.7%
1/15
|
0.00%
0/2
|
5.9%
1/17
|
|
Respiratory, thoracic and mediastinal disorders
wheezing
|
0.00%
0/11
|
0.00%
0/15
|
0.00%
0/2
|
5.9%
1/17
|
|
Ear and labyrinth disorders
ear ache
|
0.00%
0/11
|
6.7%
1/15
|
0.00%
0/2
|
0.00%
0/17
|
|
Infections and infestations
sore throat
|
9.1%
1/11
|
6.7%
1/15
|
0.00%
0/2
|
5.9%
1/17
|
|
Infections and infestations
stuffy nose
|
54.5%
6/11
|
13.3%
2/15
|
50.0%
1/2
|
23.5%
4/17
|
|
Skin and subcutaneous tissue disorders
pain at the injection site
|
0.00%
0/11
|
13.3%
2/15
|
0.00%
0/2
|
47.1%
8/17
|
|
Skin and subcutaneous tissue disorders
tenderness at the injection site
|
0.00%
0/11
|
20.0%
3/15
|
0.00%
0/2
|
47.1%
8/17
|
|
Skin and subcutaneous tissue disorders
swelling at the injection site
|
0.00%
0/11
|
0.00%
0/15
|
0.00%
0/2
|
5.9%
1/17
|
|
Skin and subcutaneous tissue disorders
redness at the injection site
|
0.00%
0/11
|
0.00%
0/15
|
0.00%
0/2
|
5.9%
1/17
|
Additional Information
John Treanor MD, Professor of Medicine
University of Rochester
Phone: 585-275-5871
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place