Trial Outcomes & Findings for Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants (NCT NCT00342628)
NCT ID: NCT00342628
Last Updated: 2012-06-27
Results Overview
Number of infants with Fever\>=38.0 C, Induration\>=2.5cm at DTP site, Induration\>=2.5cm,Vi-rEPA/Hib-TT site, Erythema\>=2.5cm, at DTP site, Erythema\>=2.5cm, Vi-rEPA/Hib-TT site, Inconsolable crying\<4hr, Inconsolable crying\>=4hr per injection with Vi conjugate vaccine given in conjunction with DTP in infants.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
301 participants
Primary outcome timeframe
at 2, 4, 6 and 12 months
Results posted on
2012-06-27
Participant Flow
Informed consent was obtained from expectant women during prenatal visits in Thanh Thuy District, Phu-Tho Province, Vietnam. Mothers and newborns were enrolled during labor at commune/district health centers from July 26, 2006 to March 8, 2007. Only fullterm newborns with birth weights of \>=2500 grams were enrolled.
Participant milestones
| Measure |
Vi-rEPA Plus DTP
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
|
Hib-TT Plus DTP
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
|
DTP Vaccines
DTP at 2, 4, and 6 months of age
|
|---|---|---|---|
|
Overall Study
STARTED
|
100
|
101
|
100
|
|
Overall Study
COMPLETED
|
80
|
80
|
81
|
|
Overall Study
NOT COMPLETED
|
20
|
21
|
19
|
Reasons for withdrawal
| Measure |
Vi-rEPA Plus DTP
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
|
Hib-TT Plus DTP
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
|
DTP Vaccines
DTP at 2, 4, and 6 months of age
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
19
|
19
|
18
|
|
Overall Study
Death
|
1
|
1
|
0
|
|
Overall Study
moved residence
|
0
|
1
|
1
|
Baseline Characteristics
Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants
Baseline characteristics by cohort
| Measure |
Vi-rEPA Plus DTP
n=100 Participants
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
|
Hib-TT Plus DTP
n=101 Participants
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
|
DTP Vaccines
n=100 Participants
DTP at 2, 4, and 6 months of age
|
Total
n=301 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
Age at 1st injection
|
77 Days
n=5 Participants
|
76 Days
n=7 Participants
|
76 Days
n=5 Participants
|
77 Days
n=4 Participants
|
|
Age, Customized
Age at 2nd injection
|
137 Days
n=5 Participants
|
137 Days
n=7 Participants
|
137 Days
n=5 Participants
|
137 Days
n=4 Participants
|
|
Age, Customized
Age at 3rd injection
|
197 Days
n=5 Participants
|
198 Days
n=7 Participants
|
197 Days
n=5 Participants
|
197 Days
n=4 Participants
|
|
Age, Customized
Age at 4th injection
|
382 Days
n=5 Participants
|
381 Days
n=7 Participants
|
NA Days
n=5 Participants
|
382 Days
n=4 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
151 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
150 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: at 2, 4, 6 and 12 monthsPopulation: The number of infants injected in each group for each injection was used to determine the rate of adverse reactions.
Number of infants with Fever\>=38.0 C, Induration\>=2.5cm at DTP site, Induration\>=2.5cm,Vi-rEPA/Hib-TT site, Erythema\>=2.5cm, at DTP site, Erythema\>=2.5cm, Vi-rEPA/Hib-TT site, Inconsolable crying\<4hr, Inconsolable crying\>=4hr per injection with Vi conjugate vaccine given in conjunction with DTP in infants.
Outcome measures
| Measure |
Vi-rEPA Plus DTP
n=100 Participants
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
|
Hib-TT Plus DTP
n=101 Participants
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
|
DTP Vaccines
n=100 Participants
DTP at 2, 4, and 6 months of age
|
|---|---|---|---|
|
Number of Infants With Adverse Reactions After Vaccination
Inconsolable crying>=4hr, inj 2
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Inconsolable crying>=4hr, inj 3
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Inconsolable crying>=4hr, inj 4
|
0 participants
|
0 participants
|
NA participants
no injection for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Fever>=38.0 C 1st inj
|
22 participants
|
24 participants
|
17 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Fever>=38.0 C 2nd inj
|
7 participants
|
7 participants
|
6 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Fever>=38.0 C 3rd inj
|
4 participants
|
2 participants
|
0 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Fever>=38.0 C 4th inj
|
2 participants
|
0 participants
|
NA participants
no injection for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Induration>=2.5cm, at DTP site, Inj 1
|
2 participants
|
2 participants
|
5 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Induration>=2.5cm, at DTP site, Inj 2
|
1 participants
|
1 participants
|
2 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Induration>=2.5cm, at DTP site, Inj 3
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Induration>=2.5cm, at DTP site, Inj 4
|
NA participants
No injection for this group
|
NA participants
no injection for this group
|
NA participants
no injection for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Induration>=2.5cm,Vi-rEPA/Hib-TT site, Inj 1
|
1 participants
|
0 participants
|
NA participants
no Vi-rEPA/Hib-TT site for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Induration>=2.5cm,Vi-rEPA/Hib-TT site, Inj 2
|
0 participants
|
0 participants
|
NA participants
no Vi-rEPA/Hib-TT site for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Induration>=2.5cm,Vi-rEPA/Hib-TT site, Inj 3
|
0 participants
|
0 participants
|
NA participants
no Vi-rEPA/Hib-TT site for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Induration>=2.5cm,Vi-rEPA/Hib-TT site, Inj 4
|
0 participants
|
0 participants
|
NA participants
no Vi-rEPA/Hib-TT site for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Erythema>=2.5cm, at DTP site, Inj 1
|
3 participants
|
1 participants
|
4 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Erythema>=2.5cm, at DTP site, Inj 2
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Erythema>=2.5cm, at DTP site, Inj 3
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Erythema>=2.5cm, at DTP site, Inj 4
|
NA participants
No injection for this group
|
NA participants
no injection for this group
|
NA participants
no injection for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Erythema>=2.5cm, Vi-rEPA/Hib-TT site, Inj 1
|
2 participants
|
0 participants
|
NA participants
no Vi-rEPA/Hib-TT site for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Erythema>=2.5cm, Vi-rEPA/Hib-TT site, Inj 2
|
0 participants
|
0 participants
|
NA participants
no Vi-rEPA/Hib-TT site for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Erythema>=2.5cm, Vi-rEPA/Hib-TT site, Inj 3
|
0 participants
|
0 participants
|
NA participants
no Vi-rEPA/Hib-TT site for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Erythema>=2.5cm, Vi-rEPA/Hib-TT site, Inj 4
|
0 participants
|
0 participants
|
NA participants
no Vi-rEPA/Hib-TT site for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Inconsolable crying<4hr, inj 1
|
5 participants
|
7 participants
|
2 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Inconsolable crying<4hr, inj 2
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Inconsolable crying<4hr, inj 3
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Infants With Adverse Reactions After Vaccination
Inconsolable crying<4hr, inj 4
|
0 participants
|
0 participants
|
NA participants
no injection for this group
|
|
Number of Infants With Adverse Reactions After Vaccination
Inconsolable crying>=4hr, inj 1
|
2 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: cord sera, infants' sera at 7, 12 and 13 monthsPopulation: Only participants with available cord sera are included in the analyses
IgG anti-Vi was measured by ELISA and expressed as ELISA units (EU)in all sera.
Outcome measures
| Measure |
Vi-rEPA Plus DTP
n=100 Participants
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
|
Hib-TT Plus DTP
n=100 Participants
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
|
DTP Vaccines
n=100 Participants
DTP at 2, 4, and 6 months of age
|
|---|---|---|---|
|
IgG Anti-Vi Levels
IgG anti-Vi (cord sera)
|
0.66 ELISA units
Interval 0.3 to 1.46
|
0.55 ELISA units
Interval 0.26 to 1.02
|
0.52 ELISA units
Interval 0.2 to 0.98
|
|
IgG Anti-Vi Levels
IgG anti-Vi at 7 months
|
17.42 ELISA units
Interval 7.33 to 47.25
|
0.16 ELISA units
Interval 0.1 to 0.25
|
0.05 ELISA units
Interval 0.02 to 0.09
|
|
IgG Anti-Vi Levels
IgG anti-Vi at 12 months
|
4.76 ELISA units
Interval 2.2 to 12.71
|
0.17 ELISA units
Interval 0.11 to 0.27
|
0.04 ELISA units
Interval 0.02 to 0.08
|
|
IgG Anti-Vi Levels
IgG anti-Vi at 13 months
|
50.07 ELISA units
Interval 22.33 to 133.61
|
0.19 ELISA units
Interval 0.11 to 0.27
|
NA ELISA units
No serum samples were collected for this group
|
SECONDARY outcome
Timeframe: Cord sera, and infants' sera at 7, 12 and 13 months of agePopulation: Randomly chosen 30 participants in each group. Four in Comparison group 2 were excluded from analyses due to classification error.
IgG anti-diphtheria toxoid (DT), -tetanus toxoid (TT) and -pertussis toxin (PT) were measured by ELISA in sera of 30 randomly chosen infants per group.
Outcome measures
| Measure |
Vi-rEPA Plus DTP
n=30 Participants
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
|
Hib-TT Plus DTP
n=30 Participants
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
|
DTP Vaccines
n=26 Participants
DTP at 2, 4, and 6 months of age
|
|---|---|---|---|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-TT (U/ml) cord sera
|
4.81 U/ml
Interval 2.94 to 10.62
|
3.92 U/ml
Interval 1.98 to 7.58
|
4.37 U/ml
Interval 1.01 to 12.91
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-TT (U/ml) at 7 months
|
4.18 U/ml
Interval 3.18 to 6.97
|
5.16 U/ml
Interval 3.16 to 8.32
|
4.03 U/ml
Interval 2.78 to 5.28
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-TT (U/ml) at 12 months
|
0.46 U/ml
Interval 0.36 to 0.69
|
0.87 U/ml
Interval 0.73 to 1.17
|
0.53 U/ml
Interval 0.37 to 0.74
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-TT (U/ml) at 13 months
|
0.39 U/ml
Interval 0.31 to 0.56
|
5.15 U/ml
Interval 2.85 to 12.01
|
NA U/ml
No blood samples collected at 13 months
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-DT (U/ml) cord sera
|
8.29 U/ml
Interval 6.2 to 14.13
|
8.63 U/ml
Interval 4.39 to 16.65
|
11.84 U/ml
Interval 6.14 to 15.94
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-DT (U/ml) at 7 months
|
62.10 U/ml
Interval 42.25 to 96.58
|
74.56 U/ml
Interval 34.93 to 152.93
|
55.79 U/ml
Interval 41.18 to 97.3
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-DT (U/ml) at 12 months
|
8.27 U/ml
Interval 5.62 to 13.24
|
10.07 U/ml
Interval 4.95 to 18.78
|
9.10 U/ml
Interval 5.6 to 15.68
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-DT (U/ml) at 13 months
|
7.93 U/ml
Interval 6.06 to 11.19
|
8.66 U/ml
Interval 4.33 to 15.42
|
NA U/ml
No blood samples collected at 13 months.
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-PT (U/ml) cord sera
|
26.58 U/ml
Interval 18.04 to 38.86
|
33.71 U/ml
Interval 22.62 to 54.55
|
25.30 U/ml
Interval 18.36 to 39.67
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-PT (U/ml) at 7 months
|
199.72 U/ml
Interval 125.36 to 522.88
|
311.91 U/ml
Interval 166.06 to 467.77
|
283.67 U/ml
Interval 156.11 to 554.64
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-PT (U/ml) at 12 months
|
30.86 U/ml
Interval 20.38 to 77.06
|
41.03 U/ml
Interval 19.86 to 73.04
|
42.94 U/ml
Interval 28.31 to 71.89
|
|
Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Anti-PT (U/ml) at 13 months
|
25.86 U/ml
Interval 14.89 to 51.21
|
33.52 U/ml
Interval 14.51 to 70.22
|
NA U/ml
No blood samples collected at 13 months
|
SECONDARY outcome
Timeframe: Cord sera and infant sera at 7, 12, and 13 monthsPopulation: Randomly chosen 30 participants in each group. Four in Comparison group 2 were excluded from analyses due to classification error.
IgG anti-Hib CP was measured by ELISA in sera of 30 randomly chosen infants per group
Outcome measures
| Measure |
Vi-rEPA Plus DTP
n=30 Participants
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
|
Hib-TT Plus DTP
n=30 Participants
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
|
DTP Vaccines
n=30 Participants
DTP at 2, 4, and 6 months of age
|
|---|---|---|---|
|
Antibody Responses to Hib CP
Anti-Hib CP (mcg/ml) cord sera
|
2.11 mcg/ml
Interval 0.99 to 3.95
|
1.33 mcg/ml
Interval 0.75 to 3.18
|
2.0 mcg/ml
Interval 0.87 to 3.9
|
|
Antibody Responses to Hib CP
Anti-Hib CP (mcg/ml) at 7 months
|
0.32 mcg/ml
Interval 0.11 to 0.53
|
8.35 mcg/ml
Interval 2.95 to 29.65
|
0.33 mcg/ml
Interval 0.2 to 0.38
|
|
Antibody Responses to Hib CP
Anti-Hib CP (mcg/ml) at 12 months
|
0.29 mcg/ml
Interval 0.09 to 1.23
|
1.79 mcg/ml
Interval 0.98 to 3.21
|
0.37 mcg/ml
Interval 0.2 to 0.52
|
|
Antibody Responses to Hib CP
Anti-Hib CP (mcg/ml) at 13 months
|
0.29 mcg/ml
Interval 0.09 to 1.04
|
24.53 mcg/ml
Interval 10.23 to 68.26
|
NA mcg/ml
No blood samples were collected at 13 months
|
Adverse Events
Vi-rEPA Plus DTP
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Hib-TT Plus DTP
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
DTP Vaccines
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vi-rEPA Plus DTP
n=100 participants at risk
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
|
Hib-TT Plus DTP
n=101 participants at risk
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
|
DTP Vaccines
n=100 participants at risk
DTP at 2, 4, and 6 months of age
|
|---|---|---|---|
|
General disorders
Death
|
1.0%
1/100 • Number of events 1 • 2, 4, 6 and 12 months
Vaccinees were visited by health care workers at 6 hours, one and two days after each injection for measurements of temperature, inspection of injection site and record other systemic reactions.
|
0.99%
1/101 • Number of events 1 • 2, 4, 6 and 12 months
Vaccinees were visited by health care workers at 6 hours, one and two days after each injection for measurements of temperature, inspection of injection site and record other systemic reactions.
|
0.00%
0/100 • 2, 4, 6 and 12 months
Vaccinees were visited by health care workers at 6 hours, one and two days after each injection for measurements of temperature, inspection of injection site and record other systemic reactions.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place