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Study of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

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ClinicalTrials.gov Identifier: NCT01374516
Recruitment Status : Completed
First Posted : June 16, 2011
Results First Posted : March 27, 2019
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Dengue Fever
Dengue Hemorrhagic Fever
Dengue
Interventions Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus
Biological: Placebo: (NaCl) 0.9% solution
Enrollment 20869
Recruitment Details Study participants were enrolled from 08 June 2011 to 16 March 2012 at 5 clinical centers in Brazil, 9 in Colombia, 1 in Honduras, 5 in Mexico, and 2 in Puerto Rico.
Pre-assignment Details A total of 20869 participants were enrolled and randomized in the study.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months). Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Period Title: Vaccination Phase (Up to 25 Months)
Started 13920 6949
Completed 13281 6640
Not Completed 639 309
Reason Not Completed
Protocol Violation             43             14
Adverse Event             3             0
Withdrawal by Subject             480             240
Lost to Follow-up             106             46
Serious adverse event             7             9
Period Title: Surveillance Expansion Period
Started 13281 6640
Completed 10932 5387
Not Completed 2349 1253
Reason Not Completed
Protocol Violation             386             217
Withdrawal by Subject             1870             986
Lost to Follow-up             73             45
Serious adverse event             20             5
Arm/Group Title CYD Dengue Vaccine Group Placebo Group Total
Hide Arm/Group Description Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months). Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months). Total of all reporting groups
Overall Number of Baseline Participants 13920 6949 20869
Hide Baseline Analysis Population Description
Analysis was performed on all randomized participants.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13920 participants 6949 participants 20869 participants
<=18 years
13920
 100.0%
6949
 100.0%
20869
 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:  Years
Age Continuous Number Analyzed 13920 participants 6949 participants 20869 participants
12.5  (2.14) 12.5  (2.13) 12.5  (2.14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13920 participants 6949 participants 20869 participants
Female
7048
  50.6%
3532
  50.8%
10580
  50.7%
Male
6872
  49.4%
3417
  49.2%
10289
  49.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13920 participants 6949 participants 20869 participants
Colombia 6497 3246 9743
Brazil 2370 1178 3548
Mexico 2312 1152 3464
Honduras 1866 933 2799
Puerto Rico 875 440 1315
1.Primary Outcome
Title Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction (RT-PCR) and/or dengue non-structural (NS) protein 1 antigen enzyme-linked immunosorbent assay (ELISA). Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time Frame 28 days and up to 13 months post-injection 3
Hide Outcome Measure Data
Hide Analysis Population Description
Number of symptomatic VCD cases were assessed in the Per-Protocol Analysis Set for Efficacy, defined as participants who had no protocol deviations.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 12574 6261
Measure Type: Number
Unit of Measure: Cases
176 221
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine Group, Placebo Group
Comments The statistical methodology was based on the use of the two-sided 95% confidence interval (CI) of the vaccine efficacy (expressed in %). The CI was calculated using the exact method conditional on the total number of cases in both groups (exact method by Breslow & Day). The vaccine efficacy of the CYD dengue vaccine was considered significant if the lower bound of its 95% CI was greater than 25%.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 60.8
Confidence Interval (2-Sided) 95%
52.0 to 68.0
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time Frame Day 0 up to 13 months post-injection 3
Hide Outcome Measure Data
Hide Analysis Population Description
Number of symptomatic VCD cases were assessed in the Full Analysis Set for Efficacy, which included all participants who received at least 1 injection.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 13914 6940
Measure Type: Number
Unit of Measure: Cases
277 385
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine Group, Placebo Group
Comments The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy (expressed in %) calculated using the exact method conditional on the total number of cases in both groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 64.7
Confidence Interval (2-Sided) 95%
58.7 to 69.8
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time Frame 28 days post-injection 1 and up to 13 months post-injection 3
Hide Outcome Measure Data
Hide Analysis Population Description
Number of symptomatic VCD cases were assessed in the Full Analysis Set for Efficacy, which included participants who received at least 1 dose of study vaccine.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 13914 6940
Measure Type: Number
Unit of Measure: Cases
273 380
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine Group, Placebo Group
Comments The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy (expressed in %) calculated using the exact method conditional on the total number of cases in both groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 64.7
Confidence Interval (2-Sided) 95%
58.7 to 69.9
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time Frame 28 days post-injection 2 and up to 13 months post-injection 3
Hide Outcome Measure Data
Hide Analysis Population Description
Number of symptomatic VCD cases were assessed in the Other Efficacy Analysis Set, which included participants who received at least 2 doses of study vaccine.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 13506 6765
Measure Type: Number
Unit of Measure: Cases
236 306
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine Group, Placebo Group
Comments The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy (expressed in %) calculated using the exact method conditional on the total number of cases in both groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Efficacy
Estimated Value 61.9
Confidence Interval (2-Sided) 95%
54.7 to 68.0
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description Dengue hemorrhagic fever (DHF) cases were defined as number of participants with at least one symptomatic VCD episode meeting the 1997 WHO criteria. (a) Fever: acute onset, high (>= 38°C) and continuous, lasting 2 to 7 days and (b) any of the pre-listed hemorrhagic manifestations and laboratory findings of thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/ or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhage.
Time Frame Day 0 to the end of study (up to 72 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of WHO dengue hemorrhagic fever cases were assessed in the Safety Analysis Set, which included all participants who received at least one dose of study vaccine. Here, ‘overall number of participants analyzed’ = participants evaluable for this outcome measure.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 12809 6380
Measure Type: Number
Unit of Measure: Cases
Due to Any of the 4 Serotypes: Any Grade 7 15
Due to Any of the 4 Serotypes: Grade I 0 2
Due to Any of the 4 Serotypes: Grade II 7 13
Due to Any of the 4 Serotypes: Grade III 0 0
Due to Any of the 4 Serotypes: Grade IV 0 0
6.Secondary Outcome
Title Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description The 1997 WHO criteria are: a) Fever: acute onset, high (>= 38°C) and continuous, for 2 to 7 days and (b) any of the following: thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hematocrit increased by 20% or more or pleural effusion and/or ascites and/or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participant, usually in the form of skin and/or other hemorrhages; Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness; and Grade IV: Profound shock with undetectable blood pressure and pulse.
Time Frame From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of WHO dengue hemorrhagic fever cases were assessed in the Full Analysis Set for Surveillance Expansion Period, which included all participants who received at least 1 injection and accepted to be included in the Surveillance Expansion Period.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 11063 5430
Measure Type: Number
Unit of Measure: Cases
Due to Any of the 4 Serotypes: Any Grade 2 0
Due to Any of the 4 Serotypes: Grade I 0 0
Due to Any of the 4 Serotypes: Grade II 2 0
Due to Any of the 4 Serotypes: Grade III 0 0
Due to Any of the 4 Serotypes: Grade IV 0 0
7.Secondary Outcome
Title Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description Hospitalized VCD cases were defined as VCD confirmed by dengue RT–PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature >=38°C on at least 2 consecutive days) requiring hospitalization.
Time Frame Day 0 up to the end of study (up to 72 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of hospitalized dengue hemorrhagic fever cases were assessed in the Safety Analysis Set. Here, ‘overall number of participants analyzed’ = participants evaluable for this outcome measure.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Overall Number of Participants Analyzed 12809 6380
Measure Type: Number
Unit of Measure: Cases
46 71
8.Secondary Outcome
Title Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description Hospitalized VCD cases were defined as VCD confirmed by dengue RT–PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature >=38°C on at least 2 consecutive days) requiring hospitalization.
Time Frame From consent to participate in the Surveillance Expansion Period to end of the study (up to 72 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed in the Safety Analysis Set.
Arm/Group Title CYD Dengue Vaccine Group Control Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Overall Number of Participants Analyzed 13915 6939
Measure Type: Number
Unit of Measure: Cases
5 2
9.Secondary Outcome
Title Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description The severity of VCD cases was assessed by an Independent Data monitoring Committee (IDMC) based on a medical review of cases and any of the following criteria:1) Platelet count <=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20 mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by Glasgow Coma Scale (GCS) score 5) Liver impairment (AST >1000 IU/L or prothrombin time [PT] International normalized ratio [INR] >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.
Time Frame Day 0 to the end of study (up to 72 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of clinically severe VCD cases were assessed in the Safety Analysis Set. Here, ‘overall number of participants analyzed’ = participants evaluable for this outcome measure.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 12809 6380
Measure Type: Number
Unit of Measure: Cases
9 16
10.Secondary Outcome
Title Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description The severity of VCD cases was assessed by an IDMC based on a medical review of cases and any of the following criteria:-1) Platelet count <=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20 mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. Unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by GCS score 5) Liver impairment (AST >1000 IU/L or PT INR >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.
Time Frame From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Number of clinically severe VCD cases were assessed in the Full Analysis Set for Surveillance Expansion Period. Here, ‘overall number of participants analyzed’ = participants evaluable for this outcome measure.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 11061 5431
Measure Type: Number
Unit of Measure: Cases
42 34
11.Secondary Outcome
Title Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo
Hide Description Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (parental strains) were measured by the plaque reduction neutralization test in a pre-defined subset of participants.
Time Frame Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit [V] 07) and 60 months (Visit [V] 12) post-injection 3
Hide Outcome Measure Data
Hide Analysis Population Description
Antibody titers against each dengue virus serotype strain were assessed in Full Analysis Set for Immunogenicity(FASI),which included a subset of participants who received at least one dose of vaccine and had a blood sample drawn and result available after the dose.Here, ‘number analyzed’=participants with available data for each specified category.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Subset of participants who received at least one dose of CYD Dengue vaccine.
Subset of participants who received at least one dose of placebo vaccine.
Overall Number of Participants Analyzed 1301 643
Measure Type: Number
Unit of Measure: Percentage of participants
Dengue virus Serotype 1: Pre-Inj.1 Number Analyzed 1297 participants 641 participants
72.8 70.5
Dengue virus Serotype 1: Post-Inj. 2 Number Analyzed 1296 participants 638 participants
92.7 71.8
Dengue virus Serotype 1: Post-Inj. 3 Number Analyzed 1291 participants 640 participants
94.9 74.2
Dengue virus Serotype 1; 1 year Post-Inj. 3 (V 07) Number Analyzed 1261 participants 629 participants
85.6 73.6
Dengue virus Serotype 1; 5 year Post-Inj. 3 (V 12) Number Analyzed 1038 participants 508 participants
90.0 81.1
Dengue virus Serotype 2; Pre-Inj. 1 Number Analyzed 1299 participants 640 participants
76.1 73.8
Dengue virus Serotype 2; Post-Inj. 2 Number Analyzed 1297 participants 639 participants
97.5 75.1
Dengue virus Serotype 2; Post-Inj. 3 Number Analyzed 1291 participants 640 participants
98.5 77.2
Dengue virus Serotype 2; 1 year Post-Inj. 3 (V 07) Number Analyzed 1264 participants 629 participants
94.1 78.9
Dengue virus Serotype 2; 5 year Post-Inj. 3 (V 12) Number Analyzed 1038 participants 508 participants
93.5 83.1
Dengue virus Serotype 3; Pre-Inj. 1 Number Analyzed 1300 participants 639 participants
76.5 73.6
Dengue virus Serotype 3; Post-Inj. 2 Number Analyzed 1297 participants 639 participants
98.5 75.7
Dengue virus Serotype 3; Post-Inj. 3 Number Analyzed 1291 participants 640 participants
98.4 78.0
Dengue virus Serotype 3; 1 year Post-Inj. 3 (V 07) Number Analyzed 1265 participants 629 participants
92.7 76.2
Dengue virus Serotype 3; 5 year Post-Inj. 3 (V 12) Number Analyzed 1038 participants 508 participants
95.4 82.7
Dengue virus Serotype 4; Pre-Inj. 1 Number Analyzed 1297 participants 640 participants
68.2 65.0
Dengue virus Serotype 4; Post-Inj. 2 Number Analyzed 1295 participants 637 participants
96.9 67.0
Dengue virus Serotype 4; Post-Inj. 3 Number Analyzed 1291 participants 640 participants
98.1 68.9
Dengue virus Serotype 4; 1 year Post-Inj. 3 (V 07) Number Analyzed 1265 participants 625 participants
94.9 69.0
Dengue virus Serotype 4; 5 year Post-Inj. 3 (V 12) Number Analyzed 1038 participants 508 participants
96.3 78.9
12.Secondary Outcome
Title Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo
Hide Description Geometric mean titers for each of the 4 dengue virus serotypes (parental strains) were assessed using the plaque reduction neutralization test in a pre-defined subset of participants.
Time Frame Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3
Hide Outcome Measure Data
Hide Analysis Population Description
Antibody titers against each dengue virus serotype strain were assessed in FASI, which included a subset of participants who received at least one dose of vaccine and had a blood sample drawn and result available after the dose. Here,‘number analyzed’ = participants with available data for each specified category.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Subset of participants who received at least one dose of CYD Dengue vaccine.
Subset of participants who received at least one dose of the placebo vaccine.
Overall Number of Participants Analyzed 1301 643
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers (1/dilution)
Dengue virus Serotype 1; Pre-Inj. 1 Number Analyzed 1297 participants 641 participants
128
(112 to 145)
119
(98.7 to 142)
Dengue virus Serotype 1; Post Inj. 2 Number Analyzed 1296 participants 638 participants
458
(406 to 517)
128
(106 to 154)
Dengue virus Serotype 1; Post Inj. 3 Number Analyzed 1291 participants 640 participants
395
(353 to 441)
121
(101 to 145)
Dengue virus Serotype 1; Year 1 Post Inj. 3 (V 07) Number Analyzed 1261 participants 629 participants
266
(234 to 302)
146
(121 to 176)
Dengue virus Serotype 1; Year 5 Post Inj. 3 (V 12) Number Analyzed 1038 participants 508 participants
284
(252 to 321)
210
(172 to 255)
Dengue virus Serotype 2; Pre-Inj. 1 Number Analyzed 1299 participants 640 participants
138
(123 to 156)
115
(97.2 to 136)
Dengue virus Serotype 2; Post Inj. 2 Number Analyzed 1297 participants 639 participants
622
(566 to 684)
124
(104 to 148)
Dengue virus Serotype 2; Post Inj. 3 Number Analyzed 1291 participants 640 participants
574
(528 to 624)
129
(109 to 152)
Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07) Number Analyzed 1264 participants 629 participants
371
(336 to 409)
145
(122 to 173)
Dengue virus Serotype 2; Year 5 Post-Inj. 3 (V 12) Number Analyzed 1038 participants 508 participants
297
(269 to 328)
201
(168 to 242)
Dengue virus Serotype 3; Pre-Inj. 1 Number Analyzed 1300 participants 639 participants
121
(108 to 136)
114
(95.9 to 136)
Dengue virus Serotype 3; Post Inj. 2 Number Analyzed 1297 participants 639 participants
556
(506 to 610)
117
(98.3 to 139)
Dengue virus Serotype 3; Post Inj. 3 Number Analyzed 1291 participants 640 participants
508
(465 to 555)
124
(105 to 147)
Dengue virus Serotype 3; Year 1 Post Inj. 3 (V 07) Number Analyzed 1265 participants 629 participants
292
(263 to 325)
137
(114 to 165)
Dengue virus Serotype 3; Year 5 Post Inj. 3 (V 12) Number Analyzed 1038 participants 508 participants
346
(313 to 383)
224
(185 to 271)
Dengue virus Serotype 4; Pre Inj. 1 Number Analyzed 1297 participants 640 participants
43.6
(39.6 to 48.0)
39.0
(33.9 to 44.7)
Dengue virus Serotype 4; Post Inj. 2 Number Analyzed 1295 participants 637 participants
261
(242 to 281)
40.9
(35.5 to 47.0)
Dengue virus Serotype 4; Post Inj. 3 Number Analyzed 1291 participants 640 participants
241
(226 to 258)
44.3
(38.6 to 50.8)
Dengue virus Serotype 4; Year 1 Post Inj. 3 (V 07) Number Analyzed 1265 participants 625 participants
174
(161 to 188)
51.5
(44.3 to 59.8)
Dengue virus Serotype 4; Year 5 Post Inj. 3 (V 12) Number Analyzed 1038 participants 508 participants
144
(134 to 156)
73.6
(63.4 to 85.5)
13.Secondary Outcome
Title Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (9-11 years): Pain: incapacitating, unable to perform usual activities; Erythema and Swelling, >= 50 mm. Grade 3 Solicited injection site reactions (12-16 years): Pain: significant, prevents daily activity; Erythema and Swelling, >100 mm.
Time Frame Within 7 days after each and any injection
Hide Outcome Measure Data
Hide Analysis Population Description
Solicited injection site reactions were assessed in a subset of the Safety Analysis Set, which included all participants who received at least one dose of study vaccine and who were evaluated for reactogenicity. Here, ‘number analyzed’ = participants with available data for specified category.
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 1333 664
Measure Type: Number
Unit of Measure: Participants
Injection-site Pain (Post any injection) Number Analyzed 1328 participants 658 participants
650 270
Injection-site Erythema (Post-any injection) Number Analyzed 1328 participants 658 participants
83 44
Injection-site Swelling (Post-any injection) Number Analyzed 1328 participants 658 participants
77 27
Injection-site Pain (Post-injection 1) Number Analyzed 1326 participants 657 participants
430 173
Grade 3 Injection-site Pain (Post-injection 1) Number Analyzed 1326 participants 657 participants
11 6
Injection-site Erythema (Post-injection 1) Number Analyzed 1326 participants 656 participants
55 31
Grade 3 Injection-site Erythema (Post-injection 1) Number Analyzed 1326 participants 656 participants
0 1
Injection-site Swelling (Post-injection 1) Number Analyzed 1326 participants 656 participants
47 18
Grade 3 Injection-site Swelling (Post-injection 1) Number Analyzed 1326 participants 656 participants
0 1
Injection-site Pain (Post-injection 2) Number Analyzed 1297 participants 639 participants
332 105
Grade 3 Injection-site Pain (Post-injection 2) Number Analyzed 1297 participants 639 participants
7 0
Injection-site Erythema (Post-injection 2) Number Analyzed 1296 participants 639 participants
25 11
Grade 3 Injection-site Erythema (Post-injection 2) Number Analyzed 1296 participants 639 participants
1 0
Injection-site Swelling (Post-injection 2) Number Analyzed 1296 participants 639 participants
25 6
Grade 3 Injection-site Swelling (Post-injection 2) Number Analyzed 1296 participants 639 participants
0 0
Injection-site Pain (Post-injection 3) Number Analyzed 1279 participants 630 participants
288 104
Grade 3 Injection-site Pain (Post-injection 3) Number Analyzed 1279 participants 630 participants
11 2
Injection-site Erythema (Post-injection 3) Number Analyzed 1278 participants 631 participants
19 10
Grade 3 Injection-site Erythema (Post-injection 3) Number Analyzed 1278 participants 631 participants
0 0
Injection-site Swelling (Post-injection 3) Number Analyzed 1279 participants 631 participants
20 8
Grade 3 Injection-site Swelling (Post-injection 3) Number Analyzed 1279 participants 631 participants
0 0
14.Secondary Outcome
Title Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo
Hide Description Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 reactions: Fever: >= 39°C; Headache, Malaise, Myalgia, and Asthenia: significant, prevents daily activity.
Time Frame Within 14 days after each and any injection
Hide Outcome Measure Data
Hide Analysis Population Description
Solicited systemic reactions were assessed in a subset of the Safety Analysis Set, which included all participants who received at least one dose of study vaccine and who were evaluated for reactogenicity. Here, 'number analyzed' = participants with available data for specified category.
Arm/Group Title CYD Dengue Vaccine Group Control Group
Hide Arm/Group Description:
Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.
Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Overall Number of Participants Analyzed 1333 664
Measure Type: Number
Unit of Measure: Participants
Fever (Post any injection) Number Analyzed 1318 participants 654 participants
220 123
Headache (Post any injection) Number Analyzed 1328 participants 659 participants
727 379
Malaise (Post any injection) Number Analyzed 1328 participants 659 participants
536 261
Myalgia (Post any injection) Number Analyzed 1328 participants 659 participants
576 267
Asthenia (Post any injection) Number Analyzed 1328 participants 659 participants
496 251
Fever (Post-injection 1) Number Analyzed 1264 participants 635 participants
86 42
Grade 3 Fever (Post-injection 1) Number Analyzed 1264 participants 635 participants
21 7
Headache (Post-injection 1) Number Analyzed 1324 participants 657 participants
528 273
Grade 3 Headache (Post-injection 1) Number Analyzed 1324 participants 657 participants
67 27
Malaise (Post-injection 1) Number Analyzed 1323 participants 657 participants
324 170
Grade 3 Malaise (Post-injection 1) Number Analyzed 1323 participants 657 participants
32 15
Myalgia (Post-injection 1) Number Analyzed 1323 participants 657 participants
386 180
Grade 3 Myalgia (Post-injection 1) Number Analyzed 1323 participants 657 participants
29 10
Asthenia (Post-injection 1) Number Analyzed 1323 participants 657 participants
326 148
Grade 3 Asthenia (Post-injection 1) Number Analyzed 1323 participants 657 participants
36 17
Fever (Post-injection 2) Number Analyzed 1228 participants 594 participants
72 42
Grade 3 Fever (Post-injection 2) Number Analyzed 1228 participants 594 participants
10 7
Headache (Post-injection 2) Number Analyzed 1297 participants 639 participants
386 182
Grade 3 Headache (Post-injection 2) Number Analyzed 1297 participants 639 participants
27 15
Malaise (Post-injection 2) Number Analyzed 1298 participants 639 participants
270 106
Grade 3 Malaise (Post-injection 2) Number Analyzed 1298 participants 639 participants
17 8
Myalgia (Post-injection 2) Number Analyzed 1298 participants 639 participants
273 101
Grade 3 Myalgia (Post-injection 2) Number Analyzed 1298 participants 639 participants
21 5
Asthenia (Post-injection 2) Number Analyzed 1298 participants 639 participants
231 105
Grade 3 Asthenia (Post-injection 2) Number Analyzed 1298 participants 639 participants
24 7
Fever (Post-injection 3) Number Analyzed 1215 participants 597 participants
89 52
Grade 3 Fever (Post-injection 3) Number Analyzed 1215 participants 597 participants
13 5
Headache (Post-injection 3) Number Analyzed 1277 participants 631 participants
378 158
Grade 3 Headache (Post-injection 3) Number Analyzed 1277 participants 631 participants
33 12
Malaise (Post-injection 3) Number Analyzed 1277 participants 631 participants
246 96
Grade 3 Malaise (Post-injection 3) Number Analyzed 1277 participants 631 participants
18 7
Myalgia (Post-injection 3) Number Analyzed 1277 participants 631 participants
255 116
Grade 3 Myalgia (Post-injection 3) Number Analyzed 1277 participants 631 participants
19 5
Asthenia (Post-injection 3) Number Analyzed 1277 participants 631 participants
208 110
Grade 3 Asthenia (Post-injection 3) Number Analyzed 1277 participants 631 participants
17 8
Time Frame Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months).
Adverse Event Reporting Description Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
 
Arm/Group Title CYD Dengue Vaccine Group Placebo Group
Hide Arm/Group Description Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. Participants received 3 doses of placebo vaccine; one each at 0, 6, and 12 months.
All-Cause Mortality
CYD Dengue Vaccine Group Placebo Group
Affected / at Risk (%) Affected / at Risk (%)
Total   42/13915 (0.30%)      27/6939 (0.39%)    
Show Serious Adverse Events Hide Serious Adverse Events
CYD Dengue Vaccine Group Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1765/13915 (12.68%)      911/6939 (13.13%)    
Blood and lymphatic system disorders     
Anaemia  1  0/13915 (0.00%)  0 4/6939 (0.06%)  4
Anaemia Of Pregnancy  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Aplastic Anaemia  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Haemorrhagic Anaemia  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Idiopathic Thrombocytopenic Purpura  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Iron Deficiency Anaemia  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Lymphadenitis  1  7/13915 (0.05%)  7 4/6939 (0.06%)  4
Lymphadenopathy  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Lymphoid Tissue Hyperplasia  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Thrombocytopenia  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Thrombocytopenic Purpura  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Cardiac disorders     
Tachycardia  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Wolff-Parkinson-White Syndrome  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Congenital, familial and genetic disorders     
Arteriovenous Malformation  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Atrial Septal Defect  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Cryptorchism  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Hereditary Spherocytosis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Phimosis  1  0/13915 (0.00%)  0 3/6939 (0.04%)  3
Sickle Cell Trait  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Ear and labyrinth disorders     
Tympanic Membrane Perforation  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Vertigo  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Endocrine disorders     
Basedow's Disease  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Hypothalamo-Pituitary Disorder  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Eye disorders     
Keratoconus  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Retinal Detachment  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Visual Impairment  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Gastrointestinal disorders     
Abdominal Adhesions  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Abdominal Pain  1  26/13915 (0.19%)  26 9/6939 (0.13%)  9
Abdominal Pain Lower  1  3/13915 (0.02%)  3 1/6939 (0.01%)  1
Abdominal Pain Upper  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Acute Abdomen  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Anal Haemorrhage  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Colitis  1  3/13915 (0.02%)  3 4/6939 (0.06%)  4
Constipation  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Diarrhoea  1  5/13915 (0.04%)  5 4/6939 (0.06%)  4
Dyspepsia  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Enteritis  1  2/13915 (0.01%)  3 0/6939 (0.00%)  0
Enterocolitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Faecaloma  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Food Poisoning  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Gastritis  1  12/13915 (0.09%)  13 5/6939 (0.07%)  5
Gastritis Haemorrhagic  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Gastrointestinal Haemorrhage  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Gingivitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Haematemesis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Inguinal Hernia  1  5/13915 (0.04%)  5 2/6939 (0.03%)  2
Inguinal Hernia, Obstructive  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Intestinal Functional Disorder  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Intestinal Obstruction  1  1/13915 (0.01%)  1 3/6939 (0.04%)  3
Intussusception  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Irritable Bowel Syndrome  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Malocclusion  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Pancreatitis  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Pancreatitis Acute  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Peptic Ulcer  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Peritonitis  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Stomatitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Umbilical Hernia  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Umbilical Hernia, Obstructive  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Varices Oesophageal  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Vomiting  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Vomiting In Pregnancy  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
General disorders     
Catheter Site Phlebitis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Cyst  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Death  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Device Intolerance  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Discomfort  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Drowning  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Malaise  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Medical Device Complication  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Pyrexia  1  9/13915 (0.06%)  9 2/6939 (0.03%)  2
Soft Tissue Inflammation  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Sudden Death  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Hepatobiliary disorders     
Autoimmune Hepatitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Bile Duct Stone  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Cholecystitis  1  7/13915 (0.05%)  7 6/6939 (0.09%)  6
Cholecystitis Acute  1  5/13915 (0.04%)  5 2/6939 (0.03%)  2
Cholecystitis Chronic  1  3/13915 (0.02%)  3 2/6939 (0.03%)  2
Cholelithiasis  1  9/13915 (0.06%)  9 13/6939 (0.19%)  15
Cholestasis Of Pregnancy  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Gallbladder Disorder  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Hepatitis  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Hepatitis Acute  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Hepatitis Toxic  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Hydrocholecystis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Jaundice  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Immune system disorders     
Allergy To Arthropod Sting  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Anaphylactic Reaction  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Anti-Neutrophil Cytoplasmic Antibody Positive Vasculitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Antiphospholipid Syndrome  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Drug Hypersensitivity  1  1/13915 (0.01%)  1 2/6939 (0.03%)  2
Food Allergy  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Infections and infestations     
Abdominal Abscess  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Abortion Infected  1  1/13915 (0.01%)  1 2/6939 (0.03%)  2
Abscess  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Abscess Limb  1  6/13915 (0.04%)  6 1/6939 (0.01%)  1
Abscess Neck  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Abscess Of Salivary Gland  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Abscess Oral  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Acute Sinusitis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Acute Tonsillitis  1  1/13915 (0.01%)  1 4/6939 (0.06%)  4
Adenoiditis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Amniotic Cavity Infection  1  2/13915 (0.01%)  3 1/6939 (0.01%)  1
Amoebiasis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Amoebic Dysentery  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Anal Abscess  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Anogenital Warts  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Appendicitis  1  261/13915 (1.88%)  261 138/6939 (1.99%)  138
Appendicitis Perforated  1  5/13915 (0.04%)  5 2/6939 (0.03%)  2
Arthritis Bacterial  1  3/13915 (0.02%)  3 2/6939 (0.03%)  2
Arthritis Infective  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Asymptomatic Hiv Infection  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Bacterial Infection  1  3/13915 (0.02%)  3 1/6939 (0.01%)  1
Bartholin's Abscess  1  2/13915 (0.01%)  2 3/6939 (0.04%)  3
Breast Abscess  1  4/13915 (0.03%)  4 3/6939 (0.04%)  3
Breast Cellulitis  1  6/13915 (0.04%)  6 0/6939 (0.00%)  0
Bronchiolitis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Bronchitis  1  8/13915 (0.06%)  8 0/6939 (0.00%)  0
Bronchopneumonia  1  6/13915 (0.04%)  6 1/6939 (0.01%)  1
Carbuncle  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Cellulitis  1  50/13915 (0.36%)  50 35/6939 (0.50%)  35
Chikungunya Virus Infection  1  8/13915 (0.06%)  8 3/6939 (0.04%)  3
Chorioamnionitis  1  3/13915 (0.02%)  3 2/6939 (0.03%)  2
Chronic Sinusitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Chronic Tonsillitis  1  1/13915 (0.01%)  1 2/6939 (0.03%)  2
Cutaneous Anthrax  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Cystitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Dengue Fever  1  101/13915 (0.73%)  104 94/6939 (1.35%)  94
Endometritis  1  3/13915 (0.02%)  3 1/6939 (0.01%)  1
Endometritis Decidual  1  3/13915 (0.02%)  3 2/6939 (0.03%)  2
Enterocolitis Infectious  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Erysipelas  1  2/13915 (0.01%)  2 3/6939 (0.04%)  3
External Ear Cellulitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Eye Infection Toxoplasmal  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Flavivirus Infection  1  3/13915 (0.02%)  3 0/6939 (0.00%)  0
Gastroenteritis  1  34/13915 (0.24%)  34 21/6939 (0.30%)  21
Gastroenteritis Bacterial  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Gastroenteritis Viral  1  3/13915 (0.02%)  3 2/6939 (0.03%)  2
Gastrointestinal Bacterial Infection  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Gastrointestinal Infection  1  3/13915 (0.02%)  3 1/6939 (0.01%)  1
Gastrointestinal Viral Infection  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Genital Infection Female  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Genitourinary Tract Infection  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Granuloma Inguinale  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
H1n1 Influenza  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Hiv Infection  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Hiv Infection Cdc Category A3  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Helminthic Infection  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Hepatitis A  1  3/13915 (0.02%)  3 1/6939 (0.01%)  1
Hepatitis Viral  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Herpes Zoster  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Herpes Zoster Ophthalmic  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Infected Bites  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Infectious Mononucleosis  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Infective Myositis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Influenza  1  3/13915 (0.02%)  3 1/6939 (0.01%)  1
Leptospirosis  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Lower Respiratory Tract Infection  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Lung Infection  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Malaria  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Mastitis  1  4/13915 (0.03%)  4 3/6939 (0.04%)  3
Mastitis Postpartum  1  1/13915 (0.01%)  1 3/6939 (0.04%)  3
Mastoiditis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Meningitis Bacterial  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Meningitis Viral  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Mononucleosis Syndrome  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Mumps  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Mycoplasma Infection  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Nasopharyngitis  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Orchitis  1  5/13915 (0.04%)  5 2/6939 (0.03%)  2
Osteomyelitis  1  2/13915 (0.01%)  3 1/6939 (0.01%)  1
Osteomyelitis Chronic  1  4/13915 (0.03%)  4 1/6939 (0.01%)  1
Otitis Media  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Otitis Media Chronic  1  0/13915 (0.00%)  0 1/6939 (0.01%)  2
Pancreatitis Mumps  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Panencephalitis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Parasitic Gastroenteritis  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Pelvic Inflammatory Disease  1  10/13915 (0.07%)  11 4/6939 (0.06%)  4
Perineal Abscess  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Perineal Infection  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Periorbital Cellulitis  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Peritonsillar Abscess  1  2/13915 (0.01%)  2 2/6939 (0.03%)  2
Pharyngotonsillitis  1  3/13915 (0.02%)  3 0/6939 (0.00%)  0
Pilonidal Cyst  1  5/13915 (0.04%)  6 1/6939 (0.01%)  1
Pneumonia  1  18/13915 (0.13%)  18 13/6939 (0.19%)  13
Pneumonia Bacterial  1  4/13915 (0.03%)  4 0/6939 (0.00%)  0
Pneumonia Mycoplasmal  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Post Procedural Infection  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Postoperative Wound Infection  1  6/13915 (0.04%)  8 4/6939 (0.06%)  4
Postpartum Sepsis  1  4/13915 (0.03%)  4 0/6939 (0.00%)  0
Pulmonary Tuberculosis  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Pyelonephritis  1  10/13915 (0.07%)  12 0/6939 (0.00%)  0
Pyelonephritis Acute  1  7/13915 (0.05%)  7 1/6939 (0.01%)  1
Retroperitoneal Abscess  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Salmonellosis  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Scarlet Fever  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Secondary Syphilis  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Sepsis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Sinusitis  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Skin Infection  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Soft Tissue Infection  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Subcutaneous Abscess  1  13/13915 (0.09%)  13 2/6939 (0.03%)  2
Syphilis  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Tonsillitis  1  2/13915 (0.01%)  2 2/6939 (0.03%)  2
Tonsillitis Bacterial  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Tooth Abscess  1  6/13915 (0.04%)  6 2/6939 (0.03%)  3
Toxoplasmosis  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Tracheitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Tuberculosis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Typhoid Fever  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Upper Respiratory Tract Infection  1  3/13915 (0.02%)  3 3/6939 (0.04%)  3
Urinary Tract Infection  1  118/13915 (0.85%)  127 59/6939 (0.85%)  69
Urinary Tract Infection Bacterial  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Urosepsis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Vaginal Infection  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Varicella  1  3/13915 (0.02%)  3 1/6939 (0.01%)  1
Viral Cardiomyopathy  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Viral Infection  1  10/13915 (0.07%)  10 7/6939 (0.10%)  7
Visceral Leishmaniasis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Vulval Abscess  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Wound Infection  1  5/13915 (0.04%)  5 0/6939 (0.00%)  0
Injury, poisoning and procedural complications     
Abdominal Injury  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Accident  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Accident At Home  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Accident At Work  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Acetabulum Fracture  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Adverse Event Following Immunisation  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Alcohol Poisoning  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Animal Bite  1  3/13915 (0.02%)  3 3/6939 (0.04%)  3
Ankle Fracture  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Arthropod Sting  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Avulsion Fracture  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Burns Second Degree  1  6/13915 (0.04%)  6 2/6939 (0.03%)  2
Burns Third Degree  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Chemical Poisoning  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Chest Injury  1  3/13915 (0.02%)  3 2/6939 (0.03%)  2
Clavicle Fracture  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Endotracheal Intubation Complication  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Epiphyseal Fracture  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Eye Injury  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Eye Penetration  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Face Injury  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Facial Bones Fracture  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Fall  1  28/13915 (0.20%)  28 11/6939 (0.16%)  12
Femur Fracture  1  5/13915 (0.04%)  5 2/6939 (0.03%)  2
Fibula Fracture  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Foot Fracture  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Forearm Fracture  1  21/13915 (0.15%)  21 7/6939 (0.10%)  7
Foreign Body  1  1/13915 (0.01%)  1 3/6939 (0.04%)  3
Foreign Body In Eye  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Genital Injury  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Gun Shot Wound  1  24/13915 (0.17%)  24 15/6939 (0.22%)  15
Hand Fracture  1  5/13915 (0.04%)  5 3/6939 (0.04%)  3
Head Injury  1  16/13915 (0.11%)  17 3/6939 (0.04%)  3
Humerus Fracture  1  6/13915 (0.04%)  6 5/6939 (0.07%)  5
Injury  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Intentional Overdose  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Joint Dislocation  1  3/13915 (0.02%)  3 2/6939 (0.03%)  2
Joint Injury  1  5/13915 (0.04%)  5 2/6939 (0.03%)  2
Limb Crushing Injury  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Limb Injury  1  4/13915 (0.03%)  4 3/6939 (0.04%)  3
Limb Traumatic Amputation  1  4/13915 (0.03%)  4 0/6939 (0.00%)  0
Lower Limb Fracture  1  3/13915 (0.02%)  3 3/6939 (0.04%)  3
Lumbar Vertebral Fracture  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Meniscus Lesion  1  3/13915 (0.02%)  3 0/6939 (0.00%)  0
Multiple Fractures  1  6/13915 (0.04%)  6 1/6939 (0.01%)  1
Multiple Injuries  1  12/13915 (0.09%)  12 3/6939 (0.04%)  3
Muscle Injury  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Nerve Injury  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Open Wound  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Perineal Laceration  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Pneumothorax Traumatic  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Poisoning  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Poisoning Deliberate  1  15/13915 (0.11%)  16 10/6939 (0.14%)  10
Post Procedural Haemorrhage  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Post-Traumatic Pain  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Postoperative Wound Complication  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Procedural Complication  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Radius Fracture  1  8/13915 (0.06%)  8 3/6939 (0.04%)  3
Road Traffic Accident  1  108/13915 (0.78%)  109 39/6939 (0.56%)  39
Skull Fracture  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Soft Tissue Injury  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Spinal Cord Injury  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Spinal Cord Injury Cervical  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Sports Injury  1  8/13915 (0.06%)  8 3/6939 (0.04%)  3
Stab Wound  1  5/13915 (0.04%)  5 1/6939 (0.01%)  1
Tendon Injury  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Tendon Rupture  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Testicular Injury  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Thermal Burn  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Tibia Fracture  1  5/13915 (0.04%)  5 3/6939 (0.04%)  3
Toxicity To Various Agents  1  7/13915 (0.05%)  7 4/6939 (0.06%)  4
Traumatic Brain Injury  1  5/13915 (0.04%)  5 1/6939 (0.01%)  1
Traumatic Fracture  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Ulna Fracture  1  3/13915 (0.02%)  3 0/6939 (0.00%)  0
Ulnar Nerve Injury  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Upper Limb Fracture  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Vascular Access Complication  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Wound  1  5/13915 (0.04%)  5 2/6939 (0.03%)  2
Wrist Fracture  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Investigations     
Investigation  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Diabetes Mellitus Inadequate Control  1  0/13915 (0.00%)  0 2/6939 (0.03%)  3
Diabetic Ketoacidosis  1  2/13915 (0.01%)  3 0/6939 (0.00%)  0
Hypoglycaemia  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Type 1 Diabetes Mellitus  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Musculoskeletal and connective tissue disorders     
Ankle Deformity  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Arthropathy  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Back Pain  1  4/13915 (0.03%)  4 2/6939 (0.03%)  2
Epiphysiolysis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Intervertebral Disc Protrusion  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Juvenile Arthritis  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Knee Deformity  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Myopathy  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Myositis  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Pathological Fracture  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Rhabdomyolysis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Rheumatic Fever  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Rheumatoid Arthritis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Sacroiliitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Synovial Cyst  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Systemic Lupus Erythematosus  1  2/13915 (0.01%)  2 2/6939 (0.03%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign Hydatidiform Mole  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Benign Ovarian Tumour  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Benign Pancreatic Neoplasm  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Bone Giant Cell Tumour  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Bone Sarcoma  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Brain Neoplasm Malignant  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Chondrosarcoma  1  1/13915 (0.01%)  2 0/6939 (0.00%)  0
Chronic Myeloid Leukaemia  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Desmoid Tumour  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Fibroadenoma Of Breast  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Haemangioma Of Skin  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Hodgkin's Disease  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Leukaemia  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Osteochondroma  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Osteoma  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Osteosarcoma Metastatic  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Osteosarcoma Recurrent  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Ovarian Adenoma  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Ovarian Germ Cell Teratoma Benign  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Pituitary Tumour Benign  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Thyroid Cancer  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Uterine Leiomyoma  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Nervous system disorders     
Acute Disseminated Encephalomyelitis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Acute Polyneuropathy  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Arachnoid Cyst  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Atonic Seizures  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Cerebellar Syndrome  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Complicated Migraine  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Convulsion  1  21/13915 (0.15%)  31 10/6939 (0.14%)  11
Dizziness  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Encephalitis  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Epilepsy  1  26/13915 (0.19%)  86 8/6939 (0.12%)  27
Grand Mal Convulsion  1  2/13915 (0.01%)  2 2/6939 (0.03%)  4
Guillain-Barre Syndrome  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Haemorrhage Intracranial  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Haemorrhagic Cerebral Infarction  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Headache  1  2/13915 (0.01%)  2 2/6939 (0.03%)  2
Hydrocephalus  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Hypersomnia  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Hypertensive Encephalopathy  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Idiopathic Generalised Epilepsy  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Intracranial Aneurysm  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Migraine  1  5/13915 (0.04%)  5 2/6939 (0.03%)  2
Migraine With Aura  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Migraine Without Aura  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Neuropathy Peripheral  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Partial Seizures  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Post-Traumatic Headache  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Status Epilepticus  1  3/13915 (0.02%)  3 1/6939 (0.01%)  3
Status Migrainosus  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Syncope  1  6/13915 (0.04%)  6 2/6939 (0.03%)  2
Viith Nerve Paralysis  1  5/13915 (0.04%)  5 3/6939 (0.04%)  3
Pregnancy, puerperium and perinatal conditions     
Abnormal Product Of Conception  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Abortion  1  14/13915 (0.10%)  14 6/6939 (0.09%)  6
Abortion Complete  1  9/13915 (0.06%)  9 4/6939 (0.06%)  4
Abortion Complicated  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Abortion Incomplete  1  22/13915 (0.16%)  22 9/6939 (0.13%)  9
Abortion Incomplete Complicated  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Abortion Missed  1  3/13915 (0.02%)  3 2/6939 (0.03%)  2
Abortion Of Ectopic Pregnancy  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Abortion Spontaneous  1  48/13915 (0.34%)  51 30/6939 (0.43%)  34
Abortion Spontaneous Complete  1  8/13915 (0.06%)  8 6/6939 (0.09%)  6
Abortion Spontaneous Complicated  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Abortion Spontaneous Incomplete  1  16/13915 (0.11%)  16 2/6939 (0.03%)  2
Abortion Spontaneous Incomplete Complicated  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Abortion Threatened  1  14/13915 (0.10%)  14 3/6939 (0.04%)  4
Amniorrhexis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Antepartum Haemorrhage  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Blighted Ovum  1  11/13915 (0.08%)  11 1/6939 (0.01%)  1
Cephalo-Pelvic Disproportion  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Cervical Incompetence  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Complication Of Delivery  1  4/13915 (0.03%)  4 0/6939 (0.00%)  0
Delivery  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Eclampsia  1  5/13915 (0.04%)  5 0/6939 (0.00%)  0
Ectopic Pregnancy  1  3/13915 (0.02%)  3 3/6939 (0.04%)  3
Failed Induction Of Labour  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
False Labour  1  39/13915 (0.28%)  45 14/6939 (0.20%)  14
Foetal Distress Syndrome  1  1/13915 (0.01%)  1 4/6939 (0.06%)  4
Gestational Hypertension  1  12/13915 (0.09%)  12 7/6939 (0.10%)  7
Hellp Syndrome  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
High Risk Pregnancy  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Hyperemesis Gravidarum  1  3/13915 (0.02%)  3 0/6939 (0.00%)  0
Intra-Uterine Death  1  1/13915 (0.01%)  1 3/6939 (0.04%)  3
Intrapartum Haemorrhage  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Oligohydramnios  1  12/13915 (0.09%)  12 4/6939 (0.06%)  4
Placental Insufficiency  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Postpartum Haemorrhage  1  8/13915 (0.06%)  8 5/6939 (0.07%)  5
Pre-Eclampsia  1  34/13915 (0.24%)  35 23/6939 (0.33%)  23
Premature Baby  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Premature Delivery  1  6/13915 (0.04%)  6 1/6939 (0.01%)  1
Premature Labour  1  17/13915 (0.12%)  17 6/6939 (0.09%)  6
Premature Rupture Of Membranes  1  13/13915 (0.09%)  13 2/6939 (0.03%)  2
Premature Separation Of Placenta  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Prolonged Labour  1  1/13915 (0.01%)  1 3/6939 (0.04%)  3
Puerperal Pyrexia  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Retained Placenta Or Membranes  1  2/13915 (0.01%)  2 2/6939 (0.03%)  2
Retained Products Of Conception  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Ruptured Ectopic Pregnancy  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Stillbirth  1  6/13915 (0.04%)  6 5/6939 (0.07%)  5
Threatened Labour  1  7/13915 (0.05%)  7 9/6939 (0.13%)  10
Psychiatric disorders     
Abnormal Behaviour  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Acute Psychosis  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Acute Stress Disorder  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Adjustment Disorder  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Aggression  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Anorexia Nervosa  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Anxiety Disorder  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Bipolar I Disorder  1  2/13915 (0.01%)  4 0/6939 (0.00%)  0
Bipolar Disorder  1  2/13915 (0.01%)  2 3/6939 (0.04%)  3
Completed Suicide  1  2/13915 (0.01%)  2 2/6939 (0.03%)  2
Conduct Disorder  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Conversion Disorder  1  3/13915 (0.02%)  3 1/6939 (0.01%)  1
Dependence  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Depression  1  18/13915 (0.13%)  18 9/6939 (0.13%)  9
Depression Suicidal  1  0/13915 (0.00%)  0 2/6939 (0.03%)  2
Dissociative Disorder  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Drug Abuse  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Drug Dependence  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Intentional Drug Misuse  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Intentional Self-Injury  1  6/13915 (0.04%)  6 2/6939 (0.03%)  2
Intermittent Explosive Disorder  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Major Depression  1  6/13915 (0.04%)  6 2/6939 (0.03%)  2
Obsessive Rumination  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Psychotic Disorder  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Schizophrenia  1  1/13915 (0.01%)  1 2/6939 (0.03%)  2
Schizophrenia, Undifferentiated Type  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Somatoform Disorder  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Substance Abuse  1  14/13915 (0.10%)  15 9/6939 (0.13%)  13
Suicidal Ideation  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Suicide Attempt  1  19/13915 (0.14%)  19 8/6939 (0.12%)  14
Renal and urinary disorders     
Calculus Ureteric  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Calculus Urethral  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Calculus Urinary  1  3/13915 (0.02%)  3 1/6939 (0.01%)  1
Cystitis Haemorrhagic  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Glomerulonephritis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Haematuria  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Lupus Nephritis  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Nephritic Syndrome  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Nephrolithiasis  1  15/13915 (0.11%)  15 5/6939 (0.07%)  5
Post Streptococcal Glomerulonephritis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Renal Colic  1  2/13915 (0.01%)  2 3/6939 (0.04%)  5
Renal Failure  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Renal Tubular Necrosis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Tubulointerstitial Nephritis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Urogenital Haemorrhage  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Reproductive system and breast disorders     
Adenomyosis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Balanitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Bartholinitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Breast Disorder  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Breast Mass  1  4/13915 (0.03%)  4 1/6939 (0.01%)  1
Breast Pain  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Coital Bleeding  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Dysfunctional Uterine Bleeding  1  3/13915 (0.02%)  5 1/6939 (0.01%)  1
Dysmenorrhoea  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Endometriosis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Epididymitis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Female Genital Tract Fistula  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Gynaecomastia  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Haematocolpos  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Haematosalpinx  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Haemorrhagic Ovarian Cyst  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Metrorrhagia  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Ovarian Cyst  1  7/13915 (0.05%)  7 5/6939 (0.07%)  5
Ovarian Cyst Ruptured  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Ovarian Torsion  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Ovulation Pain  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Pelvic Pain  1  3/13915 (0.02%)  3 0/6939 (0.00%)  0
Polycystic Ovaries  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Retrograde Menstruation  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Testicular Disorder  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Testicular Torsion  1  12/13915 (0.09%)  12 3/6939 (0.04%)  3
Uterine Cyst  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Uterine Haemorrhage  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Vaginal Haemorrhage  1  3/13915 (0.02%)  3 0/6939 (0.00%)  0
Varicocele  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Vulval Haematoma  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute Pulmonary Oedema  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Acute Respiratory Failure  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Adenoidal Hypertrophy  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Alveolitis Allergic  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Asphyxia  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Aspiration  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Asthma  1  19/13915 (0.14%)  24 17/6939 (0.24%)  22
Asthmatic Crisis  1  12/13915 (0.09%)  14 7/6939 (0.10%)  8
Bronchial Obstruction  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Epistaxis  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Haemothorax  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Nasal Septum Deviation  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Nasal Turbinate Hypertrophy  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Oropharyngeal Pain  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Pleurisy  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Pneumothorax  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Pulmonary Artery Stenosis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Pulmonary Embolism  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Pulmonary Oedema  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Respiratory Tract Haemorrhage  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Status Asthmaticus  1  5/13915 (0.04%)  6 2/6939 (0.03%)  2
Tonsillar Cyst  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Tonsillar Hypertrophy  1  5/13915 (0.04%)  5 2/6939 (0.03%)  2
Skin and subcutaneous tissue disorders     
Angioedema  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Dermatitis Atopic  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Erythema  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Erythema Nodosum  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Henoch-Schonlein Purpura  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Hypertrophic Scar  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Mechanical Urticaria  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Rash Erythematous  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Skin Fissures  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Subcutaneous Nodule  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Urticaria  1  4/13915 (0.03%)  4 0/6939 (0.00%)  0
Social circumstances     
Physical Assault  1  9/13915 (0.06%)  9 4/6939 (0.06%)  4
Sexual Abuse  1  7/13915 (0.05%)  7 4/6939 (0.06%)  4
Substance Use  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Victim Of Crime  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
Victim Of Homicide  1  5/13915 (0.04%)  5 1/6939 (0.01%)  1
Victim Of Sexual Abuse  1  1/13915 (0.01%)  1 1/6939 (0.01%)  1
Surgical and medical procedures     
Abortion Induced  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Abortion Induced Complete  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Caesarean Section  1  2/13915 (0.01%)  2 1/6939 (0.01%)  1
Cholecystectomy  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Obesity Surgery  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Scoliosis Surgery  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Surgery  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Umbilical Hernia Repair  1  0/13915 (0.00%)  0 1/6939 (0.01%)  1
Vascular disorders     
Hypertensive Crisis  1  1/13915 (0.01%)  1 0/6939 (0.00%)  0
Secondary Hypertension  1  2/13915 (0.01%)  2 0/6939 (0.00%)  0
1
Term from vocabulary, MedDra 14.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CYD Dengue Vaccine Group Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1038/1333 (77.87%)      515/664 (77.56%)    
General disorders     
Asthenia  1  500/1333 (37.51%)  771 253/664 (38.10%)  366
Injection Site Erythema  1  83/1333 (6.23%)  99 44/664 (6.63%)  52
Injection Site Pain  1  650/1333 (48.76%)  1056 270/664 (40.66%)  384
Injection Site Swelling  1  77/1333 (5.78%)  92 27/664 (4.07%)  32
Malaise  1  539/1333 (40.44%)  853 264/664 (39.76%)  383
Pyrexia  1  238/1333 (17.85%)  270 127/664 (19.13%)  142
Infections and infestations     
Influenza  1  76/1333 (5.70%)  80 37/664 (5.57%)  40
Nasopharyngitis  1  150/1333 (11.25%)  163 60/664 (9.04%)  70
Musculoskeletal and connective tissue disorders     
Myalgia  1  578/1333 (43.36%)  921 267/664 (40.21%)  400
Nervous system disorders     
Headache  1  753/1333 (56.49%)  1385 388/664 (58.43%)  652
1
Term from vocabulary, MedDra 14.0
Indicates events were collected by systematic assessment
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
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01374516     History of Changes
Other Study ID Numbers: CYD15
UTN: U1111-1116-4986 ( Other Identifier: WHO )
First Submitted: June 14, 2011
First Posted: June 16, 2011
Results First Submitted: September 25, 2016
Results First Posted: March 27, 2019
Last Update Posted: April 17, 2019