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Safety of DTaP-IPV-Hep B-PRP~T Combined Vaccine Compared to Tritanrix-HepB/Hib™ and OPV Given at Age 2, 4, and 6 Months.

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ClinicalTrials.gov Identifier: NCT00313911
Recruitment Status : Completed
First Posted : April 12, 2006
Results First Posted : November 19, 2012
Last Update Posted : April 21, 2014
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Prevention
Conditions Diphtheria
Tetanus
Pertussis
Haemophilus Influenzae Type b
Hepatitis B
Interventions Biological: DTaP-IPV-HB-PRP~T
Biological: Tritanrix-HepB/Hib
Enrollment 2133
Recruitment Details Participants were enrolled and treated from 17 July 2006 to 02 January 2008 in 1 clinical center in Mexico and 1 clinical center in Peru.
Pre-assignment Details A total of 2133 participants who met the inclusion and exclusion criteria were enrolled and vaccinated.
Arm/Group Title DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV
Hide Arm/Group Description Participants received Diphtheria (D), tetanus (T), pertussis (acellular, component) (aP), hepatitis B (hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP~T) plus a Placebo, oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age. Participants received Tritanrix-Hep B/Hib™ + oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
Period Title: Overall Study
Started 1422 [1] 711 [2]
Completed 1328 670
Not Completed 94 41
Reason Not Completed
Serious adverse event             6             1
Adverse Event             2             3
Protocol Violation             19             10
Lost to Follow-up             27             14
Withdrawal by Subject             39             12
Did not meet age criteria             1             1
[1]
N for outcomes adjusted to include participant in Group 2 that got vaccine assigned to this group.
[2]
A participant in this group mistakenly got Group 1 vaccine. N in outcomes adjusted accordingly.
Arm/Group Title DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV Total
Hide Arm/Group Description Participants received Diphtheria (D), tetanus (T), pertussis (acellular, component) (aP), hepatitis B (hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP~T) plus a Placebo, oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age. Participants received Tritanrix-Hep B/Hib™ + oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age. Total of all reporting groups
Overall Number of Baseline Participants 1422 711 2133
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1422 participants 711 participants 2133 participants
<=18 years
1422
 100.0%
711
 100.0%
2133
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Age Continuous Number Analyzed 1422 participants 711 participants 2133 participants
1.89  (0.195) 1.88  (0.197) 1.88  (0.196)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1422 participants 711 participants 2133 participants
Female
706
  49.6%
344
  48.4%
1050
  49.2%
Male
716
  50.4%
367
  51.6%
1083
  50.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1422 participants 711 participants 2133 participants
Mexico 712 355 1067
Peru 710 356 1066
1.Primary Outcome
Title Number of Participants With High Fever Observed After Either DTaP-IPV-Hep B-PRP~T or Tritanrix Hep B/Hib™ + Placebo or Tritanrix-Hep B/Hib™ + Placebo Injection.
Hide Description High fever was defined as rectal temperature equivalent to ≥ 39.6ºC.
Time Frame Day 0 up to Day 7 post-injection
Hide Outcome Measure Data
Hide Analysis Population Description
The occurrence of high fever was assessed for all enrolled and vaccinated participants, intent-to-treat (safety) population. Total numbers of participants in each group adjusted for the participant that got a vaccine assigned for the other group.
Arm/Group Title DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV
Hide Arm/Group Description:
Participants received Diphtheria (D), tetanus (T), pertussis (acellular, component) (aP), hepatitis B (hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP~T) plus a Placebo, oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
Participants received Tritanrix-Hep B/Hib™ + oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
Overall Number of Participants Analyzed 1423 710
Measure Type: Number
Unit of Measure: Participants
Post Any Dose (N = 1411, 703) 56 39
Post Dose 1 (N = 1408, 703) 5 4
Post Dose 2 (N = 1348, 681) 25 15
Post Dose 3 (N = 1328, 672) 26 23
2.Secondary Outcome
Title Geometric Mean Titers of Anti Hepatitis B Antibodies Following Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine + Placebo or Tritanrix-Hep B/Hib™ + Placebo
Hide Description Anti-hepatitis B (Hep B) antibodies were measured by automated enhanced chemiluminescence assay.
Time Frame Day 30 post-dose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Anti-hepatitis B antibody titers were assessed in a subset of the enrolled and vaccinated participants, intent-to-treat population.
Arm/Group Title DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV
Hide Arm/Group Description:
Participants received Diphtheria (D), tetanus (T), pertussis (acellular, component) (aP), hepatitis B (hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP~T) plus a Placebo, oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
Participants received Tritanrix-Hep B/Hib™ + oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
Overall Number of Participants Analyzed 184 95
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
1075
(891 to 1298)
3376
(2672 to 4338)
3.Secondary Outcome
Title Percentage of Participants Reaching Seroprotection Threshold Following Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine + Placebo or Tritanrix-Hep B/Hib™ + Placebo
Hide Description

Anti hepatitis B (Hep B) antibodies were measured by automated enhanced chemiluminescence assay.

Two Seroprotection thresholds were defined: a titer ≥ 10 mIU/mL and ≥ 100 mIU/mL, respectively.

Time Frame Day 30 post-dose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Anti-hepatitis B antibody titers were assessed in a subset of the enrolled and vaccinated participants, intent-to-treat population.
Arm/Group Title DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV
Hide Arm/Group Description:
Participants received Diphtheria (D), tetanus (T), pertussis (acellular, component) (aP), hepatitis B (hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP~T) plus a Placebo, oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
Participants received Tritanrix-Hep B/Hib™ + oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
Overall Number of Participants Analyzed 184 95
Measure Type: Number
Unit of Measure: Percentage of Participants
≥ 10 mIU/mL 100 100
≥ 100 mIU/mL 96 99
4.Secondary Outcome
Title Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Each Vaccination
Hide Description

Solicited Injection Site Reactions: Pain, Erythema, Swelling. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, Irritability.

Severe solicited reactions were defined as follows: Pain, cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling, ≥5 cm; Fever ≥39.6 ºC; Vomiting, ≥6 episodes per 24 hours or requiring parenteral hydration; Crying, >3 hours; Somnolence, sleeping most of the time or difficulty to wake up; Anorexia, refuses ≥3 feeds or refuses most feeds; Irritability, inconsolable.

Time Frame Day 0 up to Day 7 Post-injection
Hide Outcome Measure Data
Hide Analysis Population Description
Solicited injection site and systemic reactions were assessed in the enrolled and vaccinated participants, intent-to-treat (safety) population. Total numbers of participants (N) in each group adjusted for the participant that got a vaccine assigned for the other group.
Arm/Group Title DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV
Hide Arm/Group Description:
Participants received Diphtheria (D), tetanus (T), pertussis (acellular, component) (aP), hepatitis B (hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP~T) plus a Placebo, oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
Participants received Tritanrix-Hep B/Hib™ + oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
Overall Number of Participants Analyzed 1423 710
Measure Type: Number
Unit of Measure: Participants
Any Pain Post Dose 1 (N=1410, 703) 831 574
Severe Pain Post Dose 1 (N=1408, 703) 175 193
Any Pain Post Dose 2 (N=1348, 681) 744 506
Severe Pain Post Dose 2 (N=1348, 681) 105 95
Any Pain Post Dose 3 (N=1327, 672) 519 448
Severe Pain Post Dose 3 (N=1327, 672) 29 65
Any Erythema Post Dose 1 (N=1408, 703) 245 234
Severe Erythema Post Dose 1 (N=1408, 703) 11 15
Any Erythema Post Dose 2 (N=1348, 681) 427 308
Severe Erythema Post Dose 2 (N=1348, 681) 6 16
Any Erythema Post Dose 3 (N=1327, 672) 587 340
Severe Erythema Post Dose 3 (N=1327, 672) 23 12
Any Swelling Post Dose 1 (N=1406, 703) 151 188
Severe Swelling Post Dose 1 (N=1406, 703) 8 24
Any Swelling Post Dose 2 (N=1348, 681) 259 270
Severe Swelling Post Dose 2 (N=1348, 681) 3 11
Any Swelling Post Dose 3 (N=1327, 672) 400 323
Severe Swelling Post Dose 3 (N=1327, 672) 3 7
Any Pyrexia Post Dose 1 (N=1408, 703) 538 473
Severe Pyrexia Post Dose 1 (N=1408, 703) 5 4
Any Pyrexia Post Dose 2 (N=1348, 681) 675 457
Severe Pyrexia Post Dose 2 (N=1348, 681) 27 16
Any Pyrexia Post Dose 3 (N=1328, 672) 552 445
Severe Pyrexia Post Dose 3 (N=1328, 672) 30 23
Any Vomiting Post Dose 1 (N=1408, 703) 230 120
Severe Vomiting Post Dose 1 (N=1408, 703) 10 4
Any Vomiting Post Dose 2 (N=1348, 681) 152 75
Severe Vomiting Post Dose 2 (N=1348, 681) 2 4
Any Vomiting Post Dose 3 (N=1328, 672) 167 95
Severe Vomiting Post Dose 3 (N=1328, 672) 17 10
Any Crying Post Dose 1 (N=1409, 703) 800 564
Severe Crying Post Dose 1 (N=1409, 703) 21 26
Any Crying Post Dose 2 (N=1348, 681) 721 481
Severe Crying Post Dose 2 (N=1348, 681) 9 8
Any Crying Post Dose 3 (N=1327, 672) 466 391
Severe Crying Post Dose 3 (N=1327, 672) 9 8
Any Somnolence Post Dose 1 (N=1408, 703) 635 375
Severe Somnolence Post Dose 1 (N=1408, 703) 46 26
Any Somnolence Post Dose 2 (N=1348, 681) 405 247
Severe Somnolence Post Dose 2 (N=1348, 681) 16 12
Any Somnolence Post Dose 3 (N=1327, 672) 272 204
Severe Somnolence Post Dose 3 (N=1327, 672) 12 11
Any Anorexia Post Dose 1 (N=1408, 703) 388 278
Severe Anorexia Post Dose 1 (N=1408, 703) 11 14
Any Anorexia Post Dose 2 (N=1348, 681) 327 195
Severe Anorexia Post Dose 2 (N=1348, 681) 12 11
Any Anorexia Post Dose 3 (N=1327, 672) 294 189
Severe Anorexia Post Dose 3 (N=1327, 672) 18 17
Any Irritability Post Dose 1 (N=1408, 703) 945 576
Severe Irritability Post Dose 1 (N=1408, 703) 42 47
Any Irritability Post Dose 2 (N=1348, 681) 799 492
Severe Irritability Post Dose 2 (N=1348, 681) 41 25
Any Irritability Post Dose 3 (N=1327, 672) 546 416
Severe Irritability Post Dose 3 (N=1327, 672) 11 17
Time Frame Adverse event data were collected from the day of the first injection (Day 0) through 6 months after the last injection.
Adverse Event Reporting Description Total number of participants in each group adjusted for the participant that got a vaccine assigned for the other group. The number at risk for the solicited injection site and systemic reactions also reflects numbers with data.
 
Arm/Group Title DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV
Hide Arm/Group Description Participants received Diphtheria (D), tetanus (T), pertussis (acellular, component) (aP), hepatitis B (hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP~T) plus a Placebo, oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age. Participants received Tritanrix-Hep B/Hib™ + oral poliovirus vaccine (OPV) in a 3-dose series with single doses at 2, 4, and 6 months of age.
All-Cause Mortality
DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   91/1423 (6.39%)      46/710 (6.48%)    
Cardiac disorders     
Cardio Respiratory Distress * 1  0/1423 (0.00%)  0 1/710 (0.14%)  1
Congenital, familial and genetic disorders     
Hip Dysplasia * 1  0/1423 (0.00%)  0 1/710 (0.14%)  1
Gastrointestinal disorders     
Intussusception * 1  0/1423 (0.00%)  0 1/710 (0.14%)  1
Diarrhoea * 1  2/1423 (0.14%)  2 0/710 (0.00%)  0
Gastric Haemorrhage * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Gastrooesophageal reflux disease * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Inguinal Hernia, Obstructive * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
General disorders     
Pyrexia * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Hepatobiliary disorders     
Choledochal Cyst * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Infections and infestations     
Abscess Neck * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Bronchiolitis * 1  12/1423 (0.84%)  12 6/710 (0.85%)  6
Bronchopneumonia * 1  13/1423 (0.91%)  13 3/710 (0.42%)  3
Encephalitis viral * 1  0/1423 (0.00%)  0 1/710 (0.14%)  1
Gastroenteritis * 1  21/1423 (1.48%)  21 18/710 (2.54%)  18
Gastroenteritis rotavirus * 1  1/1423 (0.07%)  1 1/710 (0.14%)  1
Kawasaki's disease * 1  0/1423 (0.00%)  0 1/710 (0.14%)  1
Laryngotracheitis * 1  2/1423 (0.14%)  2 0/710 (0.00%)  0
Lymphangitis * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Periorbital Cellulitis * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Pharyngitis * 1  2/1423 (0.14%)  2 0/710 (0.00%)  0
Pneumonia * 1  5/1423 (0.35%)  5 3/710 (0.42%)  3
Pneumonia viral * 1  6/1423 (0.42%)  6 2/710 (0.28%)  2
Postoperative Wound Infection * 1  0/1423 (0.00%)  0 1/710 (0.14%)  1
Pyoderma * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Pyoderma Streptococcal * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Urinary Tract Infection * 1  1/1423 (0.07%)  1 1/710 (0.14%)  1
Injury, poisoning and procedural complications     
Head Injury * 1  2/1423 (0.14%)  2 3/710 (0.42%)  3
Nervous system disorders     
Encephalitis * 1  1/1423 (0.07%)  1 1/710 (0.14%)  1
Epilepsy * 1  1/1423 (0.07%)  1 1/710 (0.14%)  1
Febrile Convulsion * 1  4/1423 (0.28%)  4 1/710 (0.14%)  1
Hypotonic Hyporesponsive Episode * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Subarachnoid Haemorrhage * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Bronchial Hyperactivity * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Bronchial Obstruction * 1  9/1423 (0.63%)  9 1/710 (0.14%)  1
Bronchospasm * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Foreign Body Aspiration * 1  1/1423 (0.07%)  1 0/710 (0.00%)  0
Obstructive Airways Disorder * 1  0/1423 (0.00%)  0 1/710 (0.14%)  1
Skin and subcutaneous tissue disorders     
Purpura * 1  0/1423 (0.00%)  0 1/710 (0.14%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 9.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.00%
DTaP-IPV-Hep B-PRP~T Tritanrix-Hep B/Hib™ + OPV
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   945/1423 (66.41%)      576/710 (81.13%)    
Gastrointestinal disorders     
Abdominal Pain * 1  131/1411 (9.28%)  131 70/703 (9.96%)  70
Diarrhoea * 1  264/1411 (18.71%)  264 123/703 (17.50%)  123
Solicited Vomiting Post-dose 1  1  230/1410 (16.31%)  230 120/703 (17.07%)  120
General disorders     
Solicited Injection site Erythema Post-dose 3  1  587/1410 (41.63%)  587 340/703 (48.36%)  340
Injection Site Haemorrhage * 1  39/1411 (2.76%)  39 63/703 (8.96%)  63
Injection Site Nodule * 1  81/1411 (5.74%)  81 79/703 (11.24%)  79
Solicited Injection Site Pain Post-dose 1  1  831/1410 (58.94%)  831 574/703 (81.65%)  574
Solicited Injection Site Swelling Post-dose 3  1  400/1408 (28.41%)  400 323/703 (45.95%)  323
Solicited Irritability post-dose 1  1  945/1410 (67.02%)  945 576/703 (81.93%)  576
Solicited Pyrexia Post-dose 2  1  675/1411 (47.84%)  675 457/703 (65.01%)  457
Infections and infestations     
Gastroenteritis * 1  101/1411 (7.16%)  101 40/703 (5.69%)  40
Nasopharyngitis * 1  742/1411 (52.59%)  742 353/703 (50.21%)  353
Pharyngitis * 1  395/1411 (27.99%)  395 161/703 (22.90%)  161
Rhinitis * 1  136/1411 (9.64%)  136 56/703 (7.97%)  56
Metabolism and nutrition disorders     
Solicited Anorexia Post-dose 1  1  388/1410 (27.52%)  388 278/703 (39.54%)  278
Nervous system disorders     
Solicited Somnolence Post-dose 1  1  635/1410 (45.04%)  635 375/703 (53.34%)  375
Psychiatric disorders     
Solicited Crying Post-dose 1  1  800/1411 (56.70%)  800 564/703 (80.23%)  564
Respiratory, thoracic and mediastinal disorders     
Bronchospasm * 1  163/1411 (11.55%)  163 74/703 (10.53%)  74
Rhinitis Allergic * 1  75/1411 (5.32%)  75 36/703 (5.12%)  36
Skin and subcutaneous tissue disorders     
Dermatitis Diaper * 1  160/1411 (11.34%)  160 54/703 (7.68%)  54
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 9.0
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
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Sanofi Pasteur Inc.
EMail: RegistryContactUs@sanofipasteur.com
Layout table for additonal information
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00313911     History of Changes
Other Study ID Numbers: A3L04
First Submitted: April 11, 2006
First Posted: April 12, 2006
Results First Submitted: September 18, 2012
Results First Posted: November 19, 2012
Last Update Posted: April 21, 2014