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

NCT01983553 | Completed Results DMC

• 2 other identifiers: CYD57U1111-1127-7380
• Study Type: observational
• Target: 3,203
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Dengue; Dengue Fever; Dengue Hemorrhagic Fever

Keywords

Dengue Virus; Dengue Fever; Dengue Hemorrhagic Fever; CYD Dengue Vaccine

Outcome Measures

Primary Outcomes (14)

• 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

Study Arms (2)

CYD Dengue Vaccine Group

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

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.

Eligibility Criteria

• Age: 7 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Participants in study CYD23 (NCT00842530) who were hospitalized with dengue cases.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (1)

Unknown Facility

Ratchaburi, Muang District, Thailand

Location

Related Publications (3)

• Forrat R, Dayan GH, DiazGranados CA, Bonaparte M, Laot T, Capeding MR, Sanchez L, Coronel DL, Reynales H, Chansinghakul D, Hadinegoro SRS, Perroud AP, Frago C, Zambrano B, Machabert T, Wu Y, Luedtke A, Price B, Vigne C, Haney O, Savarino SJ, Bouckenooghe A, Noriega F. Analysis of Hospitalized and Severe Dengue Cases Over the 6 years of Follow-up of the Tetravalent Dengue Vaccine (CYD-TDV) Efficacy Trials in Asia and Latin America. Clin Infect Dis. 2021 Sep 15;73(6):1003-1012. doi: 10.1093/cid/ciab288.

  PMID: 33822015 DERIVED

• Sridhar S, Luedtke A, Langevin E, Zhu M, Bonaparte M, Machabert T, Savarino S, Zambrano B, Moureau A, Khromava A, Moodie Z, Westling T, Mascarenas C, Frago C, Cortes M, Chansinghakul D, Noriega F, Bouckenooghe A, Chen J, Ng SP, Gilbert PB, Gurunathan S, DiazGranados CA. Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy. N Engl J Med. 2018 Jul 26;379(4):327-340. doi: 10.1056/NEJMoa1800820. Epub 2018 Jun 13.

  PMID: 29897841 DERIVED

• Hadinegoro SR, Arredondo-Garcia JL, Capeding MR, Deseda C, Chotpitayasunondh T, Dietze R, Muhammad Ismail HI, Reynales H, Limkittikul K, Rivera-Medina DM, Tran HN, Bouckenooghe A, Chansinghakul D, Cortes M, Fanouillere K, Forrat R, Frago C, Gailhardou S, Jackson N, Noriega F, Plennevaux E, Wartel TA, Zambrano B, Saville M; CYD-TDV Dengue Vaccine Working Group. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease. N Engl J Med. 2015 Sep 24;373(13):1195-206. doi: 10.1056/NEJMoa1506223. Epub 2015 Jul 27.

  PMID: 26214039 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Dengue; Severe Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Results Point of Contact

• Title: Director
• Organization: Sanofi Pasteur SA

Contact-US@sanofi.com

Study Officials

• Medical Director

  Sanofi Pasteur SA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2013
• First Posted: November 14, 2013
• Study Start: September 10, 2013
• Primary Completion: June 15, 2016
• Study Completion: August 1, 2016
• Last Updated: March 29, 2022
• Results First Posted: July 29, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

TH (1)