ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00342628
Recruitment Status : Completed
First Posted : June 21, 2006
Results First Posted : June 27, 2012
Last Update Posted : June 27, 2012
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Typhoid Fever
Interventions Biological: Vi-rEPA conjugate vaccine for typhoid fever
Biological: Hib-TT
Biological: DTP
Enrollment 301
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines
Hide Arm/Group Description Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age DTP at 2, 4, and 6 months of age
Period Title: Overall Study
Started 100 101 100
Completed 80 [1] 80 [2] 81 [3]
Not Completed 20 21 19
Reason Not Completed
Withdrawal by Subject             19             19             18
Death             1             1             0
moved residence             0             1             1
[1]
84 completed 4 injections, 4 were lost-to-followup after the 4th injection
[2]
83 completed 4 injections, 3 were lost-to-followup after 4th injection
[3]
97 completed 3 injections of DTP alone, 16 were lost-to-followup for blood drawing at 12 months.
Arm/Group Title Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines Total
Hide Arm/Group Description Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age DTP at 2, 4, and 6 months of age Total of all reporting groups
Overall Number of Baseline Participants 100 101 100 301
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized   [1] 
Mean (Full Range)
Unit of measure:  Days
Number Analyzed 100 participants 101 participants 100 participants 301 participants
Age at 1st injection
77
(61 to 92)
76
(61 to 92)
76
(61 to 92)
77
(61 to 92)
Age at 2nd injection
137
(121 to 151)
137
(120 to 154)
137
(121 to 151)
137
(120 to 154)
Age at 3rd injection
197
(181 to 212)
198
(182 to 211)
197
(181 to 211)
197
(181 to 212)
Age at 4th injection
382
(365 to 420)
381
(365 to 406)
NA [2] 
(NA to NA)
382
(365 to 420)
[1]
Measure Description: Study participants are infants recruited at birth, injected with experimental and comparison vaccine at 2, 4, 6 and 12 months of age.
[2]
No injection given
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 101 participants 100 participants 301 participants
Female
52
  52.0%
53
  52.5%
46
  46.0%
151
  50.2%
Male
48
  48.0%
48
  47.5%
54
  54.0%
150
  49.8%
1.Primary Outcome
Title Number of Infants With Adverse Reactions After Vaccination
Hide Description 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.
Time Frame at 2, 4, 6 and 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The number of infants injected in each group for each injection was used to determine the rate of adverse reactions.
Arm/Group Title Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines
Hide Arm/Group Description:
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
DTP at 2, 4, and 6 months of age
Overall Number of Participants Analyzed 100 101 100
Measure Type: Number
Unit of Measure: participants
Fever>=38.0 C 1st inj 22 24 17
Fever>=38.0 C 2nd inj 7 7 6
Fever>=38.0 C 3rd inj 4 2 0
Fever>=38.0 C 4th inj 2 0 NA [1] 
Induration>=2.5cm, at DTP site, Inj 1 2 2 5
Induration>=2.5cm, at DTP site, Inj 2 1 1 2
Induration>=2.5cm, at DTP site, Inj 3 0 0 0
Induration>=2.5cm, at DTP site, Inj 4 NA [1]  NA [1]  NA [1] 
Induration>=2.5cm,Vi-rEPA/Hib-TT site, Inj 1 1 0 NA [2] 
Induration>=2.5cm,Vi-rEPA/Hib-TT site, Inj 2 0 0 NA [2] 
Induration>=2.5cm,Vi-rEPA/Hib-TT site, Inj 3 0 0 NA [2] 
Induration>=2.5cm,Vi-rEPA/Hib-TT site, Inj 4 0 0 NA [2] 
Erythema>=2.5cm, at DTP site, Inj 1 3 1 4
Erythema>=2.5cm, at DTP site, Inj 2 0 0 0
Erythema>=2.5cm, at DTP site, Inj 3 0 0 0
Erythema>=2.5cm, at DTP site, Inj 4 NA [1]  NA [1]  NA [1] 
Erythema>=2.5cm, Vi-rEPA/Hib-TT site, Inj 1 2 0 NA [2] 
Erythema>=2.5cm, Vi-rEPA/Hib-TT site, Inj 2 0 0 NA [2] 
Erythema>=2.5cm, Vi-rEPA/Hib-TT site, Inj 3 0 0 NA [2] 
Erythema>=2.5cm, Vi-rEPA/Hib-TT site, Inj 4 0 0 NA [2] 
Inconsolable crying<4hr, inj 1 5 7 2
Inconsolable crying<4hr, inj 2 0 0 0
Inconsolable crying<4hr, inj 3 0 0 0
Inconsolable crying<4hr, inj 4 0 0 NA [1] 
Inconsolable crying>=4hr, inj 1 2 1 0
Inconsolable crying>=4hr, inj 2 0 0 0
Inconsolable crying>=4hr, inj 3 0 0 0
Inconsolable crying>=4hr, inj 4 0 0 NA [1] 
[1]
no injection for this group
[2]
no Vi-rEPA/Hib-TT site for this group
2.Secondary Outcome
Title IgG Anti-Vi Levels
Hide Description IgG anti-Vi was measured by ELISA and expressed as ELISA units (EU)in all sera.
Time Frame cord sera, infants' sera at 7, 12 and 13 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only participants with available cord sera are included in the analyses
Arm/Group Title Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines
Hide Arm/Group Description:
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
DTP at 2, 4, and 6 months of age
Overall Number of Participants Analyzed 100 100 100
Geometric Mean (Inter-Quartile Range)
Unit of Measure: ELISA units
IgG anti-Vi (cord sera)
0.66
(0.30 to 1.46)
0.55
(0.26 to 1.02)
0.52
(0.20 to 0.98)
IgG anti-Vi at 7 months
17.42
(7.33 to 47.25)
0.16
(0.10 to 0.25)
0.05
(0.02 to 0.09)
IgG anti-Vi at 12 months
4.76
(2.20 to 12.71)
0.17
(0.11 to 0.27)
0.04
(0.02 to 0.08)
IgG anti-Vi at 13 months
50.07
(22.33 to 133.61)
0.19
(0.11 to 0.27)
NA [1] 
(NA to NA)
[1]
No serum samples were collected for this group
3.Secondary Outcome
Title Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
Hide Description 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.
Time Frame Cord sera, and infants' sera at 7, 12 and 13 months of age
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomly chosen 30 participants in each group. Four in Comparison group 2 were excluded from analyses due to classification error.
Arm/Group Title Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines
Hide Arm/Group Description:
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
DTP at 2, 4, and 6 months of age
Overall Number of Participants Analyzed 30 30 26
Geometric Mean (Inter-Quartile Range)
Unit of Measure: U/ml
Anti-TT (U/ml) cord sera
4.81
(2.94 to 10.62)
3.92
(1.98 to 7.58)
4.37
(1.01 to 12.91)
Anti-TT (U/ml) at 7 months
4.18
(3.18 to 6.97)
5.16
(3.16 to 8.32)
4.03
(2.78 to 5.28)
Anti-TT (U/ml) at 12 months
0.46
(0.36 to 0.69)
0.87
(0.73 to 1.17)
0.53
(0.37 to 0.74)
Anti-TT (U/ml) at 13 months
0.39
(0.31 to 0.56)
5.15
(2.85 to 12.01)
NA [1] 
(NA to NA)
Anti-DT (U/ml) cord sera
8.29
(6.20 to 14.13)
8.63
(4.39 to 16.65)
11.84
(6.14 to 15.94)
Anti-DT (U/ml) at 7 months
62.10
(42.25 to 96.58)
74.56
(34.93 to 152.93)
55.79
(41.18 to 97.30)
Anti-DT (U/ml) at 12 months
8.27
(5.62 to 13.24)
10.07
(4.95 to 18.78)
9.10
(5.60 to 15.68)
Anti-DT (U/ml) at 13 months
7.93
(6.06 to 11.19)
8.66
(4.33 to 15.42)
NA [2] 
(NA to NA)
Anti-PT (U/ml) cord sera
26.58
(18.04 to 38.86)
33.71
(22.62 to 54.55)
25.30
(18.36 to 39.67)
Anti-PT (U/ml) at 7 months
199.72
(125.36 to 522.88)
311.91
(166.06 to 467.77)
283.67
(156.11 to 554.64)
Anti-PT (U/ml) at 12 months
30.86
(20.38 to 77.06)
41.03
(19.86 to 73.04)
42.94
(28.31 to 71.89)
Anti-PT (U/ml) at 13 months
25.86
(14.89 to 51.21)
33.52
(14.51 to 70.22)
NA [1] 
(NA to NA)
[1]
No blood samples collected at 13 months
[2]
No blood samples collected at 13 months.
4.Secondary Outcome
Title Antibody Responses to Hib CP
Hide Description IgG anti-Hib CP was measured by ELISA in sera of 30 randomly chosen infants per group
Time Frame Cord sera and infant sera at 7, 12, and 13 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomly chosen 30 participants in each group. Four in Comparison group 2 were excluded from analyses due to classification error.
Arm/Group Title Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines
Hide Arm/Group Description:
Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age
Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age
DTP at 2, 4, and 6 months of age
Overall Number of Participants Analyzed 30 30 30
Geometric Mean (Inter-Quartile Range)
Unit of Measure: mcg/ml
Anti-Hib CP (mcg/ml) cord sera
2.11
(0.99 to 3.95)
1.33
(0.75 to 3.18)
2.0
(0.87 to 3.90)
Anti-Hib CP (mcg/ml) at 7 months
0.32
(0.11 to 0.53)
8.35
(2.95 to 29.65)
0.33
(0.20 to 0.38)
Anti-Hib CP (mcg/ml) at 12 months
0.29
(0.09 to 1.23)
1.79
(0.98 to 3.21)
0.37
(0.20 to 0.52)
Anti-Hib CP (mcg/ml) at 13 months
0.29
(0.09 to 1.04)
24.53
(10.23 to 68.26)
NA [1] 
(NA to NA)
[1]
No blood samples were collected at 13 months
Time Frame 2, 4, 6 and 12 months
Adverse Event Reporting Description 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.
 
Arm/Group Title Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines
Hide Arm/Group Description Vi-rEPA plus DTP at 2, 4, 6 and Vi-rEPA at 12 months of age Hib-TT plus DTP at 2,4,6 and Hib-TT at 12 months of age DTP at 2, 4, and 6 months of age
All-Cause Mortality
Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/100 (1.00%)      1/101 (0.99%)      0/100 (0.00%)    
General disorders       
Death * [1]  1/100 (1.00%)  1 1/101 (0.99%)  1 0/100 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
A 5 month old injected 1 X with Vi-rEPA died of septicemia post surgery for "nonfunctioning" kidneys. A 4 month old died of pneumonia after 2nd injection of Hib-TT. Deaths were unrelated to study, noted only because they affect the participant flow.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vi-rEPA Plus DTP Hib-TT Plus DTP DTP Vaccines
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/100 (0.00%)      0/101 (0.00%)      0/100 (0.00%)    
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Feng-Ying (Kimi) Lin, MD, MPH
Organization: PDMI, NICHD, NIH
Phone: 301-496-0295
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier: NCT00342628     History of Changes
Other Study ID Numbers: 999999050
OH99-CH-N050 ( Registry Identifier: NICHD IRB )
First Submitted: June 19, 2006
First Posted: June 21, 2006
Results First Submitted: March 30, 2012
Results First Posted: June 27, 2012
Last Update Posted: June 27, 2012