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    Clinical Trial Results:
    Large Scale Safety Study of a DTaP IPV Hep B PRP T Combined Vaccine, in Comparison to Tritanrix Hep B/Hib™ and OPV Administered at 2, 4, and 6 Months of Age in Latin American Infants

    Summary
    EudraCT number
    		 2011-004431-31
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    02 Jan 2008

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Feb 2016
    First version publication date
    31 Jul 2014
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A3L04
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00313911
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Sanofi Pasteur SA
    Sponsor organisation address
    2, avenue Pont Pasteur, Lyon cedex, France, F 69367
    Public contact
    Director, Clinical Development, Sanofi Pasteur SA, 33 (0)4 37 37 58 43 , emmanuel.feroldi@sanofipasteur.com
    Scientific contact
    Director, Clinical Development, Sanofi Pasteur SA, 33 (0)4 37 37 58 43 , emmanuel.feroldi@sanofipasteur.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001201-PIP01-11
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    10 Jul 2008
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jan 2008
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that DTaP-IPV-Hep B-PRP-T combined vaccine + OPV placebo does not induce a higher incidence rate of high fever than Tritanrix-Hep B/Hib™ + OPV after any of the three vaccinations at 2, 4, and 6 months of age for each subject.
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate equipment were also available on site in case of any immediate allergic reactions.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Jul 2006
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Mexico: 1067
    Country: Number of subjects enrolled
    Peru: 1066
    Worldwide total number of subjects
    2133
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    2133
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Eligible subjects that met all the inclusion and none of the exclusion criteria were enrolled and vaccinated in the study.

    Pre-assignment
    Screening details
    		 A total of 2133 participants who met the inclusion and non of the exclusion criteria were enrolled and vaccinated.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Investigator [1]
    Blinding implementation details
    The investigator (blind observer or assessor) and subject’s parents or guardians did not know the vaccine administered. The assessor was in charge of the assessment of safety held in a separate room and away from where the vaccines were prepared. A nurse/vaccinator was in charge of the preparation and administration of the vaccine(s) in another room away from the assessor. When necessary the scratch off emergency decoding procedure described in the study protocol were to be followed.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 DTaP-IPV-Hep B-PRP~T Group
    Arm 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Hexaxim
    Investigational medicinal product code
    DTaP-IPV-HepB-PRP-T vaccine
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, administered at 2, 4, and 6 months of age.

    Investigational medicinal product name
    OPV Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    0.1 mL, oral administration

    Arm title
    		 Tritanrix-Hep B/Hib™ + OPV Group
    Arm description
    		 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.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tritanrix HepB/Hib™
    Investigational medicinal product code
    Tritanrix HepB/Hib™
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular

    Investigational medicinal product name
    OPVERO (Oral Poliomyelitis Vaccine)
    Investigational medicinal product code
    OPV
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Each dose is 0.1 mL administered by Oral route.

    Notes
    [1] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: The investigator of the study served as observer or assessor that was masked for the actual vaccine administered to each subject.
    Number of subjects in period 1
    		DTaP-IPV-Hep B-PRP~T Group Tritanrix-Hep B/Hib™ + OPV Group
    Started
    1422
    711
    Completed
    1328
    670
    Not completed
    94
    41
         Consent withdrawn by subject
    39
    12
         Adverse event, non-fatal
    2
    3
         Lost to follow-up
    27
    14
         Serious Adverse Events
    6
    1
         ' Did not meet age criteria'
    1
    1
         Protocol deviation
    19
    10

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    DTaP-IPV-Hep B-PRP~T Group
    Reporting 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.

    Reporting group title
    Tritanrix-Hep B/Hib™ + OPV Group
    Reporting group description
    		 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.

    Reporting group values
    		 DTaP-IPV-Hep B-PRP~T Group Tritanrix-Hep B/Hib™ + OPV Group Total
    Number of subjects
    		 1422 711 2133
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 1422 711 2133
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    		 1.89 ( 0.195 ) 1.88 ( 0.197 ) -
    Gender categorical
    Units: Subjects
        Female
    		 706 344 1050
        Male
    		 716 367 1083

    End points

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    End points reporting groups
    Reporting group title
    DTaP-IPV-Hep B-PRP~T Group
    Reporting 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.

    Reporting group title
    Tritanrix-Hep B/Hib™ + OPV Group
    Reporting group description
    		 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.

    Primary: 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

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    End point 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
    End point description
    High fever was defined as rectal temperature equivalent to ≥ 39.6ºC.
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 7 post-injection
    End point values
    		 DTaP-IPV-Hep B-PRP~T Group Tritanrix-Hep B/Hib™ + OPV Group
    Number of subjects analysed
    1422 [1]
    711 [2]
    Units: Participants
        Post Any Dose
    56
    39
        Post Dose 1
    5
    4
        Post Dose 2
    25
    15
        Post Dose 3
    26
    23
    Notes
    [1] - N for outcomes adjusted to include participant in Group 2 that got vaccine assigned to this group.
    [2] - A subject in this group mistakenly got Group 1 vaccine. N in outcomes adjusted accordingly
    Statistical analysis title
    		 High Fever Post-vaccination
    Statistical analysis description
    The occurrence of at least one high fever episode (≥39.6°C rectal temperature equivalent) observed within 7 days after any of the three injections and the resulting risk ratio
    Comparison groups
    DTaP-IPV-Hep B-PRP~T Group v Tritanrix-Hep B/Hib™ + OPV Group
    Number of subjects included in analysis
    2133
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 1.07
    Notes
    [3] - Confidence interval was calculated using the normal approximation for the log transformation of Risk Ratio (RR) as described by Blackwelder

    Secondary: 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

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    End point 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
    End point description
    Anti-hepatitis B (Hep B) antibodies were measured by automated enhanced chemiluminescence assay.
    End point type
    Secondary
    End point timeframe
    Day 30 post-dose 3
    End point values
    		 DTaP-IPV-Hep B-PRP~T Group Tritanrix-Hep B/Hib™ + OPV Group
    Number of subjects analysed
    184
    95
    Units: Titers
    geometric mean (confidence interval 95%)
        Anti Hepatitis B Antibodies
    1075 (891 to 1298)
    3376 (2672 to 4338)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Reaching Seroprotection Threshold Following Vaccination With Either DTaP-IPV-Hep B-PRP~T Vaccine + Placebo or Tritanrix-Hep B/Hib™ + Placebo

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    End point 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
    End point 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.
    End point type
    Secondary
    End point timeframe
    Day 30 post-dose 3
    End point values
    		 DTaP-IPV-Hep B-PRP~T Group Tritanrix-Hep B/Hib™ + OPV Group
    Number of subjects analysed
    184
    95
    Units: mIU/mL
    number (not applicable)
        ≥ 10 mIU/mL
    100
    100
        ≥ 100 mIU/mL
    96
    99
    No statistical analyses for this end point

    Secondary: Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Each Vaccination

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    End point title
    		 Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Each Vaccination
    End point 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.
    End point type
    Secondary
    End point timeframe
    Day 0 up to Day 7 Post-injection
    End point values
    		 DTaP-IPV-Hep B-PRP~T Group Tritanrix-Hep B/Hib™ + OPV Group
    Number of subjects analysed
    1422
    711
    Units: Participants
        Any Pain Post Dose 1
    831
    574
        Severe Pain Post Dose 1
    175
    193
        Any Pain Post Dose 2
    744
    506
        Severe Pain Post Dose 2
    105
    95
        Any Pain Post Dose 3
    519
    448
        Severe Pain Post Dose 3
    29
    65
        Any Erythema Post Dose 1
    245
    234
        Severe Erythema Post Dose 1
    11
    15
        Any Erythema Post Dose 2
    427
    308
        Severe Erythema Post Dose 2
    6
    16
        Any Erythema Post Dose 3
    587
    340
        Severe Erythema Post Dose 3
    23
    12
        Any Swelling Post Dose 1
    151
    188
        Severe Swelling Post Dose 1
    8
    24
        Any Swelling Post Dose 2
    259
    270
        Severe Swelling Post Dose 2
    3
    11
        Any Swelling Post Dose 3
    400
    323
        Severe Swelling Post Dose 3
    3
    7
        Any Pyrexia Post Dose 1
    538
    473
        Severe Pyrexia Post Dose 1
    5
    4
        Any Pyrexia Post Dose 2
    675
    457
        Severe Pyrexia Post Dose 2
    27
    16
        Any Pyrexia Post Dose 3
    552
    445
        Severe Pyrexia Post Dose 3
    30
    23
        Any Vomiting Post Dose 1
    230
    120
        Severe Vomiting Post Dose 1
    10
    4
        Any Vomiting Post Dose 2
    152
    75
        Severe Vomiting Post Dose 2
    2
    4
        Any Vomiting Post Dose 3
    167
    95
        Severe Vomiting Post Dose 3
    17
    10
        Any Crying Post Dose 1
    800
    564
        Severe Crying Post Dose 1
    21
    26
        Any Crying Post Dose 2
    721
    481
        Severe Crying Post Dose 2
    9
    8
        Any Crying Post Dose 3
    466
    391
        Severe Crying Post Dose 3
    9
    8
        Any Somnolence Post Dose 1
    635
    375
        Severe Somnolence Post Dose 1
    46
    26
        Any Somnolence Post Dose 2
    405
    247
        Severe Somnolence Post Dose 2
    16
    12
        Any Somnolence Post Dose 3
    272
    204
        Severe Somnolence Post Dose 3
    12
    11
        Any Anorexia Post Dose 1
    388
    278
        Severe Anorexia Post Dose 1
    11
    14
        Any Anorexia Post Dose 2
    327
    195
        Severe Anorexia Post Dose 2
    12
    11
        Any Anorexia Post Dose 3
    294
    189
        Severe Anorexia Post Dose 3
    18
    17
        Any Irritability Post Dose 1
    945
    576
        Severe Irritability Post Dose 1
    42
    47
        Any Irritability Post Dose 2
    799
    492
        Severe Irritability Post Dose 2
    41
    25
        Any Irritability Post Dose 3
    546
    416
        Severe Irritability Post Dose 3
    11
    17
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse event data were collected from the day of the first injection (Day 0) through 6 months after the last injection.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    9.0
    Reporting groups
    Reporting group title
    DTaP-IPV-Hep B-PRP~T Group
    Reporting 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.

    Reporting group title
    Tritanrix-Hep B/Hib™ + OPV Group
    Reporting group description
    		 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.

    Serious adverse events
    		 DTaP-IPV-Hep B-PRP~T Group Tritanrix-Hep B/Hib™ + OPV Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    91 / 1423 (6.39%)
    46 / 710 (6.48%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    2 / 1423 (0.14%)
    3 / 710 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hip Dysplasia
         subjects affected / exposed
    0 / 1423 (0.00%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardio Respiratory Distress
         subjects affected / exposed
    0 / 1423 (0.00%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Encephalitis
         subjects affected / exposed
    1 / 1423 (0.07%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 1423 (0.07%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile Convulsion
         subjects affected / exposed
    4 / 1423 (0.28%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotonic Hyporesponsive Episode
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid Haemorrhage
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 1423 (0.14%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric Haemorrhage
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal Hernia, Obstructive
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intussusception
         subjects affected / exposed
    0 / 1423 (0.00%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Choledochal Cyst
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchial Hyperactivity
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial Obstruction
         subjects affected / exposed
    9 / 1423 (0.63%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign Body Aspiration
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive Airways Disorder
         subjects affected / exposed
    0 / 1423 (0.00%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Purpura
         subjects affected / exposed
    0 / 1423 (0.00%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess Neck
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    12 / 1423 (0.84%)
    6 / 710 (0.85%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    13 / 1423 (0.91%)
    3 / 710 (0.42%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis viral
         subjects affected / exposed
    0 / 1423 (0.00%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    21 / 1423 (1.48%)
    18 / 710 (2.54%)
         occurrences causally related to treatment / all
    0 / 21
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    1 / 1423 (0.07%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kawasaki's disease
         subjects affected / exposed
    0 / 1423 (0.00%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngotracheitis
         subjects affected / exposed
    2 / 1423 (0.14%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangitis
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periorbital Cellulitis
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    2 / 1423 (0.14%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    5 / 1423 (0.35%)
    3 / 710 (0.42%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    6 / 1423 (0.42%)
    2 / 710 (0.28%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative Wound Infection
         subjects affected / exposed
    0 / 1423 (0.00%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyoderma
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyoderma Streptococcal
         subjects affected / exposed
    1 / 1423 (0.07%)
    0 / 710 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    1 / 1423 (0.07%)
    1 / 710 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DTaP-IPV-Hep B-PRP~T Group Tritanrix-Hep B/Hib™ + OPV Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    945 / 1423 (66.41%)
    576 / 710 (81.13%)
    Nervous system disorders
    Solicited Somnolence Post-dose 1
    alternative assessment type: Systematic
         subjects affected / exposed [1]
    635 / 1410 (45.04%)
    375 / 703 (53.34%)
         occurrences all number
    635
    375
    General disorders and administration site conditions
    Solicited Vomiting Post-dose 1
    alternative assessment type: Systematic
         subjects affected / exposed [2]
    230 / 1410 (16.31%)
    120 / 703 (17.07%)
         occurrences all number
    230
    120
    Injection Site Haemorrhage
         subjects affected / exposed [3]
    39 / 1411 (2.76%)
    63 / 703 (8.96%)
         occurrences all number
    39
    63
    Solicited Injection Site Pain Post-dose 1
    alternative assessment type: Systematic
         subjects affected / exposed [4]
    831 / 1410 (58.94%)
    574 / 703 (81.65%)
         occurrences all number
    831
    574
    Solicited Injection Site Swelling Post-dose 3
    alternative assessment type: Systematic
         subjects affected / exposed
    400 / 1423 (28.11%)
    323 / 710 (45.49%)
         occurrences all number
    400
    323
    Solicited Irritability post-dose 1
         subjects affected / exposed [5]
    945 / 1410 (67.02%)
    576 / 703 (81.93%)
         occurrences all number
    945
    576
    Solicited Pyrexia Post-dose 2
    alternative assessment type: Systematic
         subjects affected / exposed [6]
    675 / 1411 (47.84%)
    457 / 703 (65.01%)
         occurrences all number
    675
    457
    Solicited Injection Site Erythema Post-dose 3
    alternative assessment type: Systematic
         subjects affected / exposed [7]
    587 / 1410 (41.63%)
    340 / 703 (48.36%)
         occurrences all number
    587
    340
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed [8]
    131 / 1411 (9.28%)
    70 / 703 (9.96%)
         occurrences all number
    131
    70
    Diarrhoea
         subjects affected / exposed [9]
    264 / 1411 (18.71%)
    123 / 703 (17.50%)
         occurrences all number
    264
    123
    Injection Site Nodule
         subjects affected / exposed [10]
    81 / 1411 (5.74%)
    79 / 703 (11.24%)
         occurrences all number
    81
    79
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed [11]
    163 / 1411 (11.55%)
    74 / 703 (10.53%)
         occurrences all number
    163
    74
    Rhinitis allergic
         subjects affected / exposed [12]
    75 / 1411 (5.32%)
    36 / 703 (5.12%)
         occurrences all number
    75
    36
    Skin and subcutaneous tissue disorders
    Dermatitis Diaper
         subjects affected / exposed [13]
    160 / 1411 (11.34%)
    54 / 703 (7.68%)
         occurrences all number
    160
    54
    Psychiatric disorders
    Solicited Crying Post-dose 1
    alternative assessment type: Systematic
         subjects affected / exposed [14]
    800 / 1411 (56.70%)
    564 / 703 (80.23%)
         occurrences all number
    800
    564
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed [15]
    101 / 1411 (7.16%)
    40 / 703 (5.69%)
         occurrences all number
    101
    40
    Nasopharyngitis
         subjects affected / exposed [16]
    742 / 1411 (52.59%)
    353 / 703 (50.21%)
         occurrences all number
    742
    353
    Pharyngitis
         subjects affected / exposed [17]
    395 / 1411 (27.99%)
    161 / 703 (22.90%)
         occurrences all number
    395
    161
    Rhinitis
         subjects affected / exposed [18]
    136 / 1411 (9.64%)
    56 / 703 (7.97%)
         occurrences all number
    136
    56
    Metabolism and nutrition disorders
    Solicited Anorexia Post-dose 1
    alternative assessment type: Systematic
         subjects affected / exposed [19]
    388 / 1410 (27.52%)
    278 / 703 (39.54%)
         occurrences all number
    388
    278
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The total number reported for this adverse event reflects those for which data were available for the event
    [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The total number reported for this adverse event reflects those for which data were available for the event.
    [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The total number reported for this adverse event reflects those for which data were available for the event.
    [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The total number reported for this adverse event reflects those for which data were available for the event.
    [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The total number reported for this adverse event reflects those for which data were available for the event.
    [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The total number reported for this solicited adverse event reflects those for which data were available for the event.
    [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The total number reported for this adverse event reflects those for which data were available for the event.
    [17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The total number reported for this adverse event reflects those for which data were available for the event.
    [18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The total number reported for this adverse event reflects those for which data were available for the event.
    [19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Nov 2005
    This amendment was implemented prior to the inclusion of the first subject. Changes revision of immunogenicity endpoints; study design from open label to blind observer with notes on procedures for blinding, randomization and vaccine allocation, and code breaking. An IDMC was also adopted to review safety data at predefined intervals.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Not Applicable

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/22531237
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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