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A Surveillance Study of Diseases Specified as Adverse Events of Special Interest, of Other Adverse Events Leading to Hospitalisation or Death, and of Meningitis in Children in Africa Prior to Implementation of the RTS,S/AS01E Candidate Vaccine

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ClinicalTrials.gov Identifier: NCT02374450
Recruitment Status : Active, not recruiting
First Posted : February 27, 2015
Last Update Posted : May 19, 2022
Sponsor:
Collaborators:
PATH
AMP (Agence de Médecine Préventive) (in French)
RAFT (Réseau en Afrique Francophone pour la Télémédecine) (in French)
Iqvia Pty Ltd
Parexel (Mobile Phone Alert System Provider)
CLS (Clinical Laboratory Services)
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:

The purpose of this pre-licensure cohort study is to estimate the incidence of adverse events of special interest (AESI), other adverse events (AE) leading to hospitalisation or death, meningitis and malaria in sub-Saharan African children under 5 years of age. The outcomes of this study will provide the baseline data for the post-licensure EPI-MALARIA-003 (115056) study that will evaluate the safety, effectiveness and impact of the RTS,S/AS01E vaccine.

An interim analysis was performed on a sub-group of study participants enrolled in active surveillance from sites where the vaccine is currently implemented, having 6 months of follow-up following the administration of dose 3 of DTP/HepB/Hib vaccine (6-12 weeks group), or 6 months after Visit 3 (mimicking the RTS,S/AS01E primary vaccination schedule) for the 5-17 months group; corresponding to Visit 5. The interim analysis concerned primary safety endpoints and the main secondary endpoints.


Condition or disease Intervention/treatment
Malaria Malaria Vaccines Procedure: Blood collection

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Study Type : Observational
Estimated Enrollment : 35334 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Study to Estimate the Incidence of Diseases Specified as Adverse Events of Special Interest, of Other Adverse Events Leading to Hospitalisation or Death, and of Meningitis in Infants and Young Children in Sub-Saharan Africa Prior to Implementation of the RTS,S/AS01E Candidate Vaccine
Actual Study Start Date : October 5, 2015
Estimated Primary Completion Date : August 2, 2022
Estimated Study Completion Date : August 2, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Active surveillance group and enhanced hospitalisation group
Children <18 months of age at time of enrolment and living in the HDSS area (active surveillance group) and children <5 years of age and hospitalised at any time during the study, living in the HDSS area (enhanced hospitalisation surveillance group).
Procedure: Blood collection
For all hospitalised children suspected of having an AESI or meningitis, a sample of 5 ml of whole blood is collected and serum is stored.




Primary Outcome Measures :
  1. Incidence of AESI [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    AESI include: Acute Disseminated Encephalomyelitis (ADEM), encephalitis,Guillain Barré Syndrome,hypotonic-hyporesponsive episode,generalised convulsive seizure,intussusception,hepatic insufficiency,renal insufficiency,juvenile chronic arthritis,Stephen-Johnson syndrome/toxic epidermal necrolysis,Henoch-Schonlein purpura,Kawasaki disease,diabetes mellitus type I,thrombocytopenia, anaphylaxis. Incidence rates are calculated by dividing the number of subjects reporting at least one event over the follow-up period by the total person-time.The minimum at-risk period for the analyses is 2 weeks (W).All AESI expected to occur between 0-13 days (D) following dose administration is analysed with an at-risk period of 2 W. The 6W-at-risk period for AESI expected to occur between 14 D-6 W. The 3M and 6M-at-risk periods are for the AESI expected to occur between 6 W-3 M and 3-6 M, respectively. The at-risk period follows any dose, with a censoring of subjects when they receive the following dose.

  2. Incidence of adverse events (AEs) leading to hospitalisation or death [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    AEs assessed in children <5 years old, included in active or enhanced hospitalisation surveillance, prior to implementation of RTS,S/AS01E. Incidence rates will be calculated by dividing the number of subjects reporting at least one event over the follow-up period by the total person-time. The at-risk periods of 7 days and 30 days will follow any dose, with a censoring of subjects when they receive the following dose.

  3. Incidence of aetiology confirmed meningitis [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    Aetiology-confirmed meningitis assessment in children <5 years old, living in the study area, prior to implementation of RTS,S/AS01E. Aetiology-confirmed meningitis is defined by the presence of symptoms and/or signs of meningitis and the identification of any known aetiologic agent (bacterial or not) in the CSF. Incidence rates will be calculated by dividing the number of subjects reporting at least one event over the follow-up period by the total person-time. An at-risk period of 12 months after any dose will be used.


Secondary Outcome Measures :
  1. Incidence of aetiology-confirmed and/or probable meningitis [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    Aetiology-confirmed and/or probable meningitis assessment in children <5 years old, living in the study area, prior to implementation of RTS,S/AS01E. Aetiology-confirmed meningitis case is defined by the presence of symptoms and/or signs of meningitis and the identification of any known aetiologic agent (bacterial or not) in the CSF. Probable meningitis case is defined by the presence of symptoms and/or signs of meningitis and no aetiologic agent identified in the CSF, but with some abnormalities detected in the CSF (e.g. turbid macroscopic aspect, positive Gram, positive antigen test, pleiocytosis, abnormal glucose or protein levels), or positive blood culture to a bacterial agent. Incidence rates will be calculated by dividing the number of subjects reporting at least one event over the follow-up period by the total person-time. An at-risk period of 12 months after any dose will be used.

  2. Incidence of probable meningitis [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]

    Probable meningitis assessed in children < 5 years old, included in active or enhanced hospitalisation surveillance, prior to implementation of RTS,S/AS01E.

    Incidence rates will be calculated by dividing the number of subjects reporting at least one event over the follow-up period by the total person-time. An at-risk period of 12 months after any dose will be used.


  3. Incidence of aetiology-confirmed, probable and/or clinically suspected meningitis [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    Aetiology-confirmed, probable and/or clinically suspected meningitis assessment in children <5 years old, living in the study area, prior to implementation of RTS,S/AS01E. Clinically suspected meningitis case is defined by the presence of symptoms and/or signs of meningitis and if a CSF sample is available and all laboratory results are normal after second line laboratory testing, or if no CSF sample is available and no alternative diagnosis. Incidence rates will be calculated by dividing the number of subjects reporting at least one event over the follow-up period by the total person-time. An at-risk period of 12 months after any dose will be used.

  4. Occurrence of meningitis cases identified at site level (first line laboratory) [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    Number of cases of meningitis based on lab testing performed at site level. Meningitis cases identified at site level (first line laboratory assessment) in children <5 years old, living in the study area, prior to implementation of RTS,S/AS01E.

  5. Occurrence of risk factors for AESI, other AE leading to hospitalisation or death, meningitis and malaria [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    Number of children <5 years old, included in active or enhanced hospitalisation surveillance, prior to implementation of RTS,S/AS01E with at least one risk.

  6. Occurrences of causes of hospitalisation (including those attributed to an AESI, other AE, meningitis, or malaria) [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    Occurrence of hospitalisation assessed in children <5 years old, included in active or enhanced hospitalisation surveillance, prior to implementation of RTS,S/AS01E.

  7. Number of deaths by cause (overall and by gender) [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    The number of deaths by cause is assessed in children <5 years old, included in active or enhanced hospitalisation surveillance, prior to implementation of RTS,S/AS01E.The analysis of death causes is classified by MedDRA and assessed overall and by gender.

  8. Incidence of febrile convulsions following administration of routine EPI vaccines [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    Febrile convulsions are assessed in children <5 years old, included in active or enhanced hospitalisation surveillance, prior to implementation of RTS,S/AS01E. Febrile convulsions are defined as generalised seizures with measured fever greater than or equal to (≥) 37.5 degrees Celsius (°C) (axillary) or reported history of fever. Incidence rates will be calculated by dividing the number of subjects reporting at least one event over the follow-up period by the total person-time. Two at-risk periods will use: the 7-day period (Days 0-6) and the 1-month period (Days 0-29) following any vaccine administration.

  9. Incidence of any malaria reported using rapid diagnostic test (RDT) and/or microscopy [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    The incidence of any malaria detected by RDT and/or microscopy is calculated by dividing the number of subjects reporting events over the follow-up period by the total person-time for children enrolled in active surveillance. Any malaria includes uncomplicated and severe cases, including cerebral malaria. Uncomplicated is defined as: Plasmodium parasitaemia greater than (>) 0 detected by microscopy and/or RDT, fever (temperature ≥ 37.5°C) and no signs of severity or evidence (clinical or laboratory) of vital organ dysfunction. Severe is defined as: P. falciparum parasitaemia > 0 detected by microscopy and/or RDT and one or more of the following: impaired consciousness, prostration, multiple convulsions, acidosis, hypoglycaemia, severe malarial anaemia, renal impairment, jaundice, pulmonary oedema, significant bleeding, shock, hyperparasitaemia. Cerebral malaria is defined as severe P. falciparum malaria with impaired consciousness.

  10. Incidence of severe malaria reported using rapid diagnostic test (RDT) and/or microscopy [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    The incidence of severe malaria detected by RDT and/or microscopy is calculated by dividing the number of subjects reporting events over the follow-up period by the total person-time for children enrolled in the study.

  11. Incidence of cerebral malaria reported using rapid diagnostic test (RDT) and/or microscopy [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    The incidence of cerebral malaria detected by RDT and/or microscopy will be calculated by dividing the number of subjects reporting events over the follow-up period by the total person-time for children enrolled in the study.

  12. Prevalence of anaemia among hospitalised children [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]

    The prevalence for anaemia is computed by dividing the number of all cases by the number of enrolled children.

    All anaemia: haemoglobin <11 grams per deciliter (g/dL). Severe anaemia: haemoglobin <7g/dL.


  13. Incidence of all-cause hospitalisations and hospitalisations attributed to malaria (including P. falciparum) [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    The hospitalisation cases are assessed in children <5 years old, included in active surveillance, prior to implementation of RTS,S/AS01E.The incidence of hospitalisation cases is calculated by dividing the number of children hospitalised during study period over the total person-time for children enrolled in active surveillance. Hospitalisation for malaria (including P. falciparum) is defined as: a hospitalised subject with malaria (including P. falciparum malaria) and for whom malaria is the primary cause of hospitalisation.

  14. Mortality rate (all-cause mortality and deaths attributed to malaria [including P. falciparum]), overall and by gender [ Time Frame: During the entire study period (From Month 0 up to Month 60) ]
    Mortality rate is calculated by dividing the number of deaths due to any cause or due to malaria over the total person-time for children enrolled in the study.



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Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

All subjects must satisfy ALL the following criteria at study entry:

  • Subjects' 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.
  • Written informed consent provided from either the parent(s) or LAR of the subject.
  • Subject living in the Health and Demographic Surveillance System (HDSS) area.
  • For enrolment in active surveillance: children must be <18 months of age. OR
  • For enrolment in enhanced hospitalisation surveillance: children must be <5 years of age and hospitalised at any time during the study.

Exclusion Criteria:

  • Child in care.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02374450


Locations
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Burkina Faso
GSK Investigational Site
Ouagadougou, Burkina Faso
GSK Investigational Site
PO BOX 02 Nouna, Burkina Faso
Ghana
GSK Investigational Site
Kintampo, Ghana
GSK Investigational Site
Navrongo, Ghana
Kenya
GSK Investigational Site
Kisumu, Kenya, 40102
Sponsors and Collaborators
GlaxoSmithKline
PATH
AMP (Agence de Médecine Préventive) (in French)
RAFT (Réseau en Afrique Francophone pour la Télémédecine) (in French)
Iqvia Pty Ltd
Parexel (Mobile Phone Alert System Provider)
CLS (Clinical Laboratory Services)
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02374450    
Other Study ID Numbers: 115055
First Posted: February 27, 2015    Key Record Dates
Last Update Posted: May 19, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by GlaxoSmithKline:
Malaria
Surveillance study
Adverse Events of Specific Interest (AESI)
Children
Infants
Adverse events (AE) leading to hospitalisation or death
Meningitis
Epidemiology
Africa
Additional relevant MeSH terms:
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Malaria
Meningitis
Protozoan Infections
Parasitic Diseases
Infections
Vector Borne Diseases
Central Nervous System Diseases
Nervous System Diseases