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A Cohort Study to Determine the Incidence of Dengue Fever and to Build Capacity for Dengue Vaccine Trials in Dengue-endemic Regions of South Asia

Primary Purpose

Dengue

Status

Completed

Phase

Not Applicable

Locations

Sri Lanka

Study Type

Interventional

Intervention

Blood sample collection

About this trial

This is an interventional other trial for Dengue focused on measuring Dengue, Non-laboratory confirmed dengue (non-LCD), Acute febrile illness (AFI), Laboratory confirmed dengue (LCD)

Eligibility Criteria

6 Months - 50 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Subject and/or subject's parent(s)/legally acceptable representative(s) (LAR[s]) who, in the opinion of the investigator, can and will comply with the requirements of the protocol. (e.g., willingness to go to the hospital/clinic for visit[s] in case of AFI, able to observe the signs of dengue and to understand how to take and report body temperature, etc.).
Signed/thumb-printed (and video recorded if required by law) informed consent (and assent if applicable) must be obtained from the subject/subject's parent(s)/LAR(s) at the hospital/clinic or during a home visit. If the subject/subject's parent(s)/LAR(s) are illiterate, the informed consent form (ICF) (or informed assent form [IAF] when applicable) will be countersigned by an impartial witness.
Subject is part of a household with at least one child (aged less than 18 years) and in which informed consent (and assent if applicable) to study participation was obtained from at least one adult and one child.
Male or female aged between and including 6 months and 50 years at the time of enrolment.
Subject who plans, at the time of enrolment, to remain at same residence/study area during the two-year study period.

Exclusion Criteria:

Child in care.
Participation (current or planned) in another epidemiological study or in a clinical trial that would conflict with the current study, based on investigator's judgement.
Terminal illness based on investigator's judgement.
Mental incapacity based on investigator's judgement.

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AFI Group

Arm Description

Population living in randomly selected households in geographically-defined communities. Households including at least one member aged less than 18 years will be considered eligible if at least one adult (aged no more than 50 years) and one child (aged less than 18 years) consent (and assent if applicable) to participate in the study.

Outcomes

Primary Outcome Measures

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Dengue (LCD) Overall, and by Age Group

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to LCD) OR date of last contact OR date of death. An AFI due to LCD was confirmed if all of the following criteria were met: Fever (body temperature greater than or equal to (≥) 38°Celsius [C]/≥ 100.4°Farhenheit [F] on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart AND Laboratory confirmation of dengue through dengue Reverse Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR) on acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F).

Secondary Outcome Measures

Incidence Rate of Acute Febrile Illness (AFI) Due to Non-Laboratory Confirmed Dengue (Non-LCD) Overall, and by Age Group

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to non-LCD) OR date of last contact OR date of death. An AFI due to non-LCD was confirmed if all of the following criteria were met: Fever (body temperature ≥ 38°C/≥ 100.4°F) on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart, AND Dengue RT-qPCR result on the acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F) was (valid but) negative for dengue.

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Sero Type 1 Dengue Overall, and by Age Group.

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to LCD Sero Type 1) OR date of last contact OR date of death. An AFI due to LCD Sero Type 1 was confirmed if all of the following criteria were met: Fever (body temperature greater than or equal to (≥) 38°C/≥ 100.4°F on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart AND Laboratory confirmation of dengue Sero Type 1 through RT-qPCR on acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F).

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Sero Type 2 Dengue Overall, and by Age Group

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to LCD Sero Type 2) OR date of last contact OR date of death. An AFI due to LCD Sero Type 2 was confirmed if all of the following criteria were met: Fever (body temperature greater than or equal to (≥) 38°C/≥ 100.4°F on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart AND Laboratory confirmation of dengue Sero Type 2 through RT-qPCR on acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F).

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Sero Type 3 Dengue Overall, and by Age Group

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to LCD Sero Type 3) OR date of last contact OR date of death. An AFI due to LCD Sero Type 3 was confirmed if all of the following criteria were met: Fever (body temperature greater than or equal to (≥) 38°C/≥ 100.4°F on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart AND Laboratory confirmation of dengue Sero Type 3 through RT-qPCR on acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F)

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Sero Type 4 Dengue Overall, and by Age Group

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to LCD Sero Type 4) OR date of last contact OR date of death. An AFI due to LCD Sero Type 4 was confirmed if all of the following criteria were met: Fever (body temperature greater than or equal to (≥) 38°C/≥ 100.4°F on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart AND Laboratory confirmation of dengue Sero Type 4 through RT-qPCR on acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F)

Number of Acute Febrile Illness Due to Laboratory Confirmed Dengue Presenting a Sign or a Symptom of Interest (Any Intensity) During the 7-day Period Following the Onset of Each Episode of AFI Due to LCD.

Description of signs and symptoms of AFI due to LCD included the percentage of AFI presenting each sign or symptom (any intensity) during the 7-day period from the onset of fever (body temperature 38°C/100.4°F).

Number of Acute Febrile Illness Due to Laboratory Confirmed Dengue Presenting a Sign or a Symptom of Interest (Grade 3) During the 7-day Period Following the Onset of Each Episode of AFI Due to LCD

Description of signs and symptoms of AFI due to LCD included the percentage of AFI presenting each sign or symptom (grade 3) during the 7-day period from the onset of fever (body temperature 38°C/100.4°F).

Number of Acute Febrile Illness Due to Non-Laboratory Confirmed Dengue Presenting a Sign or a Symptom of Interest (Any Intensity) During the 7-day Period Following the Onset of Each Episode of AFI Due to Non-LCD

Description of signs and symptoms of AFI due to non-LCD included the percentage of AFI presenting each sign or symptom (any intensity) during the 7-day period from the onset of fever (body temperature 38°C/100.4°F).

Number of Acute Febrile Illness Due to Non-Laboratory Confirmed Dengue Presenting a Sign or a Symptom of Interest (Grade 3) During the 7-day Period Following the Onset of Each Episode of AFI Due to Non-LCD

Description of signs and symptoms of AFI due to non-LCD included the percentage of AFI presenting each sign or symptom (grade 3) during the 7-day period from the onset of fever (body temperature 38°C/100.4°F).

Number of Subjects With Serious Adverse Events (SAEs) Related to a Study Procedure

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Full Information

NCT ID

NCT02570152

First Posted

October 5, 2015

Last Updated

June 16, 2020

Sponsor

GlaxoSmithKline

Collaborators

Ministry of Health, Sri Lanka

1. Study Identification

Unique Protocol Identification Number

NCT02570152

Brief Title

A Cohort Study to Determine the Incidence of Dengue Fever and to Build Capacity for Dengue Vaccine Trials in Dengue-endemic Regions of South Asia

Official Title

A Cohort Study to Determine the Incidence of Dengue Fever and to Build Capacity for Dengue Vaccine Trials in Dengue-endemic Regions of South Asia

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

June 1, 2016 (Actual)

Primary Completion Date

June 28, 2019 (Actual)

Study Completion Date

June 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

Collaborators

Ministry of Health, Sri Lanka

4. Oversight

5. Study Description

Brief Summary

The purpose of this study is to determine the incidence of dengue fever and to build capacity for dengue vaccine trials in dengue-endemic regions of South Asia.

Detailed Description

This study aims to estimate the burden of dengue illness in selected sites South Asia and to prepare sites for the conduct of future vaccine efficacy trials. Operational goals include: Build long-term collaboration with sites in dengue-endemic regions of South Asia where the incidence of clinical dengue illness can be studied. Establish dengue surveillance cohorts that can be followed long-term. Establish operational feasibility of future Phase III studies with regard to recruitment, case capture and sampling procedures. Prepare sites for participation in Phase III clinical endpoint studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dengue

Keywords

Dengue, Non-laboratory confirmed dengue (non-LCD), Acute febrile illness (AFI), Laboratory confirmed dengue (LCD)

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2004 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AFI Group

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Blood sample collection

Intervention Description

Blood samples will be collected during the Suspected Dengue First Visit. All study subjects with AFI (fever [body temperature ≥ 38°C/≥ 100.4°F] on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart) should be seen at a designated study hospital/clinic by the study physician. The Suspected Dengue First Visit should be scheduled within 7 days from the onset of fever (Days 2-7) and should ideally take place on the second day of fever (Day 2).

Primary Outcome Measure Information:

Title

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Dengue (LCD) Overall, and by Age Group

Description

Time Frame

From first visit to last visit (approximatively 2 years per subject)

Secondary Outcome Measure Information:

Title

Incidence Rate of Acute Febrile Illness (AFI) Due to Non-Laboratory Confirmed Dengue (Non-LCD) Overall, and by Age Group

Description

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to non-LCD) OR date of last contact OR date of death. An AFI due to non-LCD was confirmed if all of the following criteria were met: Fever (body temperature ≥ 38°C/≥ 100.4°F) on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart, AND Dengue RT-qPCR result on the acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F) was (valid but) negative for dengue.

Time Frame

From first visit to last visit (approximatively 2 years per subject)

Title

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Sero Type 1 Dengue Overall, and by Age Group.

Description

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to LCD Sero Type 1) OR date of last contact OR date of death. An AFI due to LCD Sero Type 1 was confirmed if all of the following criteria were met: Fever (body temperature greater than or equal to (≥) 38°C/≥ 100.4°F on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart AND Laboratory confirmation of dengue Sero Type 1 through RT-qPCR on acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F).

Time Frame

From first visit to last visit (approximatively 2 years per subject)

Title

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Sero Type 2 Dengue Overall, and by Age Group

Description

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to LCD Sero Type 2) OR date of last contact OR date of death. An AFI due to LCD Sero Type 2 was confirmed if all of the following criteria were met: Fever (body temperature greater than or equal to (≥) 38°C/≥ 100.4°F on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart AND Laboratory confirmation of dengue Sero Type 2 through RT-qPCR on acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F).

Time Frame

From first visit to last visit (approximatively 2 years per subject)

Title

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Sero Type 3 Dengue Overall, and by Age Group

Description

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to LCD Sero Type 3) OR date of last contact OR date of death. An AFI due to LCD Sero Type 3 was confirmed if all of the following criteria were met: Fever (body temperature greater than or equal to (≥) 38°C/≥ 100.4°F on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart AND Laboratory confirmation of dengue Sero Type 3 through RT-qPCR on acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F)

Time Frame

From first visit to last visit (approximatively 2 years per subject)

Title

Incidence Rate of Acute Febrile Illness (AFI) Due to Laboratory Confirmed Sero Type 4 Dengue Overall, and by Age Group

Description

The incidence rate of first event (IR per 1000 person-years) was calculated by dividing the number of subjects reporting at least one episode of event during the follow-up period by the total person-year at risk. The person-time at risk for an event of interest was calculated as the duration between the date of enrolment and the end of the at-risk period or the earliest of the following: onset date of event of interest (e.g. first episode of AFI due to LCD Sero Type 4) OR date of last contact OR date of death. An AFI due to LCD Sero Type 4 was confirmed if all of the following criteria were met: Fever (body temperature greater than or equal to (≥) 38°C/≥ 100.4°F on ≥ 2 consecutive calendar days, measured at least twice, at least 8 hours apart AND Laboratory confirmation of dengue Sero Type 4 through RT-qPCR on acute serum sample taken during the 7-day period (Days 2-7) from the onset of fever (body temperature ≥ 38°C/≥ 100.4°F)

Time Frame

From first visit to last visit (approximatively 2 years per subject)

Title

Description

Time Frame

At each day during the 7-day period following the onset of each episode of AFI due to LCD

Title

Number of Acute Febrile Illness Due to Laboratory Confirmed Dengue Presenting a Sign or a Symptom of Interest (Grade 3) During the 7-day Period Following the Onset of Each Episode of AFI Due to LCD

Description

Time Frame

At each day during the 7-day period following the onset of each episode of AFI due to LCD

Title

Description

Time Frame

At each day during the 7-day period following the onset of each episode of AFI due to non-LCD

Title

Description

Time Frame

At each day during the 7-day period following the onset of each episode of AFI due to non-LCD

Title

Number of Subjects With Serious Adverse Events (SAEs) Related to a Study Procedure

Description

Time Frame

From first visit to last visit (approximatively 2 years per subject)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject and/or subject's parent(s)/legally acceptable representative(s) (LAR[s]) who, in the opinion of the investigator, can and will comply with the requirements of the protocol. (e.g., willingness to go to the hospital/clinic for visit[s] in case of AFI, able to observe the signs of dengue and to understand how to take and report body temperature, etc.). Signed/thumb-printed (and video recorded if required by law) informed consent (and assent if applicable) must be obtained from the subject/subject's parent(s)/LAR(s) at the hospital/clinic or during a home visit. If the subject/subject's parent(s)/LAR(s) are illiterate, the informed consent form (ICF) (or informed assent form [IAF] when applicable) will be countersigned by an impartial witness. Subject is part of a household with at least one child (aged less than 18 years) and in which informed consent (and assent if applicable) to study participation was obtained from at least one adult and one child. Male or female aged between and including 6 months and 50 years at the time of enrolment. Subject who plans, at the time of enrolment, to remain at same residence/study area during the two-year study period. Exclusion Criteria: Child in care. Participation (current or planned) in another epidemiological study or in a clinical trial that would conflict with the current study, based on investigator's judgement. Terminal illness based on investigator's judgement. Mental incapacity based on investigator's judgement.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Colombo

Country

Sri Lanka

12. IPD Sharing Statement

Citations:

PubMed Identifier

34724624

Citation

Tissera H, Samaraweera P, de Boer M, Gandhi S, Malvaux L, Mehta S, Palihawadana P, Vantomme V, Paris R, Schmidt A. The Burden of Acute Febrile Illness Attributable to Dengue Virus Infection in Sri Lanka: A Single-Center 2-Year Prospective Cohort Study (2016-2019). Am J Trop Med Hyg. 2021 Nov 1;106(1):160-167. doi: 10.4269/ajtmh.21-0604.

Results Reference

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A Cohort Study to Determine the Incidence of Dengue Fever and to Build Capacity for Dengue Vaccine Trials in Dengue-endemic Regions of South Asia

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