Long-Term Study of Hospitalized Dengue & Safety in Thai Children Included in a Tetravalent Dengue Vaccine Efficacy Study

Study Overview
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Brief Summary
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The purpose of this study was to conduct a passive surveillance of hospitalized dengue cases in participants who participated in study CYD23 (NCT00842530). The Objectives: To describe the incidence of virologically-confirmed hospitalized dengue cases. To characterize hospitalized dengue cases. To evaluate the occurrence of related and fatal serious adverse events (SAEs).

Detailed Description
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This study was a passive surveillance of hospitalized dengue cases in participants who participated in study CYD23 (NCT00842530) where participants were initially randomized to receive 3 injections of either CYD dengue vaccine or control at 6 month intervals. Any SAE related to a study procedure or related to a previous injection from study CYD23, or any fatal SAEs (even if unrelated) were reported to the Sponsor. An Independent Data Monitoring Committee (IDMC) was also involved in the regular review of virologically-confirmed hospitalized dengue cases. Any fatal outcome or related SAE were be promptly reviewed by the IDMC. No study vaccinations were administered.

Official Title
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Long-Term Follow-Up of Hospitalized Dengue and Safety in Thai Children Who Were Included in an Efficacy Study of a Tetravalent Dengue Vaccine

Conditions
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Dengue, Dengue Fever, Dengue Hemorrhagic Fever

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ongoing participation in study CYD23 at the time of enrolment. Assent form was signed and dated by the participant (for participants >= 7 years old), and informed consent form was signed and dated by the parent(s) or another legally accepted representative and by 2 independent witnesses. Participant and parent/legally accepted representative were able to attend all scheduled visits to comply with all study procedures. Exclusion Criteria: Planned participation in another dengue clinical trial during the present study Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CYD Dengue Vaccine Group<br>Participants who received 3 injections of 0.5 milliliter (mL) CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23. | |
| Control Group<br>Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively in the study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Rate Per 100 Participant-years for Hospitalized Virologically-Confirmed Dengue (VCD) Cases Due to Any and Each Serotype Following Vaccination With Either CYD Dengue Vaccine or Placebo in the Previous Study (CYD23) | Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With Either CYD Dengue Vaccine or a Placebo in a Previous Study (CYD23) | Cases were defined as the number of participants with at least one hospitalized VCD episode. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Number of Episodes of Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With Either CYD Dengue Vaccine or a Placebo in a Previous Study (CYD23) | Episodes were defined as the number of hospitalized VCD episodes. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Event Rate Per 100 Participant-years for Hospitalized VCD Cases Due to Any and Each Serotype Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) | Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) | Cases were defined as the number of participants with at least one hospitalized VCD episode. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Number of Episodes of Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) | Episodes were defined as the number of hospitalized VCD episodes. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Event Rate Per 100 Participant-years for Clinically Severe Hospitalized VCD Cases Due to Any and Each Serotype Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) | Event rate per 100 participant-years for Clinically Severe hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Number of Clinically Severe Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) | Cases were defined as the number of participants with at least one hospitalized VCD episode. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Number of Episodes of Clinically Severe Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) | Episodes were defined as the number of hospitalized VCD episodes. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Number of Cases of Non-Serotype Specific Dengue Viremia Among Hospitalized VCD Cases Following Vaccination With CYD Dengue Vaccine or Placebo in Previous Study (CYD23) | Cases were defined as the number of participants with at least one non-serotype specific dengue viremia among hospitalized VCD cases. | During Year 1 to Year 4 post 3rd vaccination at Month 12 in CYD23 at each of the following time points: Anytime, 0-3 days, 4-7 days, 0-7 days, After 7 days during the sera sample collection time interval of 14 days | 
| Non-Serotype Specific Dengue Viremia Among Hospitalized VCD Cases Following Vaccination With CYD Dengue Vaccine or Placebo in Previous Study (CYD23) | Quantified viremia was defined as greater than or equal to (>=) lower limit of quantitation (log10 plaque forming unit [pfu]/mL). | Year 1 to Year 4 post-vaccination after 3rd vaccination at Month 12 in CYD23 at each of the following time points: Anytime, 0-3 days, 4-7 days, 0-7 days, After 7 days during the sample collection time interval of 14 days | 
| Event Rate Per 100 Participant-years for Hospitalized VCD Cases Due to Any and Each Serotype and Meeting World Health Organization (WHO) 1997 Criteria Collected Following Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) | Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1. The WHO criteria were fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue haemorrhagic fever was graded as 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 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. Grade IV: Profound shock with undetectable blood pressure and pulse. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) and Meeting WHO 1997 Criteria Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) | Cases were defined as the number of participants with at least one hospitalized VCD episode meeting WHO criteria. The WHO criteria was fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue hemorrhagic fever was graded as - Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation was 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 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. Grade IV: Profound shock with undetectable blood pressure and pulse. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 
| Number of Episodes of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) and Meeting WHO 1997 Criteria Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) | Episodes were defined as the number of hospitalized virologically confirmed dengue episodes meeting WHO criteria. The WHO criteria was fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue haemorrhagic fever was graded as 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 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. Grade IV: Profound shock with undetectable blood pressure and pulse. | Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dengue Virus, Dengue Fever, Dengue Hemorrhagic Fever, CYD Dengue Vaccine