Evaluation and Support to EVD Cured Patients and Their Contacts (Les Vainqueurs d'Ebola)

Ebola Virus Disease Clinical Trial

Official title:

Evaluation and Support to Ebola Virus Disease Cured Patients and Their Contacts in the Democratic Republic of the Congo

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04409405
• Other study ID #: C19-59
• Secondary ID: ESP/CE/287/2019
• Status: Completed
• Start date: April 16, 2020
• Est. completion date: October 18, 2021

Study information

• Verified date: February 2022
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Ebola virus is one of the most dangerous human pathogens and is an emerging public health problem in sub-Saharan Africa. Ebola virus disease (EVD) first appeared in 1976. The current epidemic in the Democratic Republic of the Congo (DRC) is one of the largest and most complex ever recorded, and is not yet under control: a new death has been reported on April 10th, 2020. The epidemic was declared a public health emergency of international scope by the World Health Organization (WHO) on July 17th, 2019.

Two studies are the "standard" in the assessment of the consequences of infection in survivors, in Liberia (PREVAIL) and Guinea (PostEbogui), especially in:

• The observation of comparable mortality rates, even if over time there was an improvement in survival, probably linked to the improvement in the quality of care and symptomatic treatment;

• And the study of the contacts of the survivors, between 4 to 10% of them had done seroconversion with regard to Ebola virus (EBOV) in an asymptomatic or pauci-symptomatic way and that this rate varied according to the degree of exposure to the risk.

The DRC's experience in this area and the enormous progress made in the fight against Viral hemorrhagic fevers (VHFs), therapeutically and preventively (where much of which patients have benefited from antiviral treatment or monoclonal antibodies), the technological responses (real-time sequencing of Ebola strains in new cases, vaccination or the use of individual isolation units), show the limits of their effectiveness. A large number of questions therefore remain unanswered:

• The antibody profile of the survivors, in particular the repertoire of immunoglobulin G (IgG) specific to these individuals and its correlation with survival and its evolution over time;

• The impact of treatments initiated during the acute phase on these immune abnormalities;

• Finally, genetic factors linked to the host could play an important role in the response to the Ebola virus.

The aim of this study is to provide a better overall understanding of Ebola virus infection and its clinical, virological, and immunological consequences, of cured people and their contacts; strengthen multidisciplinary monitoring of patients after an acute phase of EVD. The results will therefore have a direct impact on the clinical management of this population and on the prevention of possible secondary contamination in the Democratic Republic of the Congo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 787
• Est. completion date: October 18, 2021
• Est. primary completion date: October 18, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

Inclusion Criteria:

In cured population

• Age = 5 years

• Adults and children after an acute episode declared cured of biologically confirmed Ebola virus disease (two negative PCRs are required at least 24 hours apart so that a patient without clinical symptoms can leave the Ebola treatment center),

• Informed consent signed by at least one of the two parents or the legal guardian authorizing the child's participation in the study,

• Volunteer participant who signed the informed consent for adults.

In CONTACT population

• Age = 5 years,

• Be a contact person of a cured patient (ie patient with a proven EVD, and with two negative PCRs at least 24 hours apart) included in the cohort of Ebola Winners. Based on WHO recommendations and the Centers for Disease Control and Prevention for the identification and traceability of contact subjects: a contact person is defined as a person who encountered the index case during his EVD in his residence, ie having the same place of life as him,

• Have not been diagnosed with EVD,

• Participation agreement:

• For adult participants (= 18 years old, emancipated or married): informed consent intended for the adult participant signed,

• For minors = 5 years old: informed consent intended for the parent(s)/legal guardian signed by at least one of the two parents or the legal guardian and assent form intended for the minor participant completed.

In cellular immunological sub-study:

• Adult participants in the parent study = 18 years old,

• Accept to participate in this sub-study

• Negative blood EBOV PCR

Exclusion Criteria:

• Absence of possible follow-up over 12 months from a logistical or geographical point of view (only for cured patients);

• Non-residents in the DRC;

• Impossibility of complying with the requirements and procedures of the study in the opinion of the investigator;

• Inability to consent.

Related Conditions & MeSH terms

• Ebola Virus Disease
• Hemorrhagic Fever, Ebola
• Virus Diseases

Locations

Country	Name	City	State
Congo, The Democratic Republic of the	Beni Hospital	Beni
Congo, The Democratic Republic of the	Butembo Hospital	Butembo
Congo, The Democratic Republic of the	Mambasa Hospital	Mambasa
Congo, The Democratic Republic of the	Mangina Hospital	Mangina

Sponsors (3)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France	Institut de Recherche pour le Developpement, Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo

Country where clinical trial is conducted

Congo, The Democratic Republic of the, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cured-participant population co-infections	Frequencies of co-infections (human immunodeficiency virus, hepatitis B virus, hepatitis C virus)	Baseline (BL)
Primary	Cured-participant population co-morbidities at any time in the study	Frequencies of co-morbidities including severity	Baseline (BL), month 3, month 6, month 9, month 12, month 18
Primary	Evolution over time of clinical consequences in cured participants	Sequelae of EVD in cured participants and their evolution according to clinical characteristics and received treatment during hospitalisation.	Baseline (BL), month 3, month 6, month 9, month 12, month 18
Primary	Evolution over time of immunological consequences in cured participants	Proportion and evolution of IgG subclasses against nucleoprotein, VP40 and glycoprotein from isolates Mayinga1976 and Kissidougou-Makona2014.	Baseline (BL), month 6, month 12
Primary	Evolution over time of virological consequences in cured participants	Evolution of EBOV virus identified by polymerase chain reaction (PCR) in biological samples (blood, urine, feces, saliva, tears, breast milk (breastfeeding women), genital secretions (women aged 15 and over) and sperm (men aged 15 and over)).	Baseline (BL), month 3, month 6, month 9, month 12, month 18
Primary	Description of contact-participants Ebola-virus-exposure risk	Description of exposure to the confirmed index case (duration and repetition of exposure, possible protection used, state of contagiousness of the confirmed index case including clinical condition and viremia), prevalence of EVD (living or deceased, with whom the subject was in contact), vaccination status against EVD.	Baseline (BL)
Primary	Asymptomatic or pauci-symptomatic Ebola infections in contact participants (clinical assessment)	Clinical assessment for EBOV infection since contact exposure to EVD patient.	Baseline (BL)
Primary	Asymptomatic or pauci-symptomatic Ebola infections in contact participants (immunological assessment)	Titration of IgG subclasses against nucleoprotein, VP40 and glycoprotein.	Baseline (BL)
Primary	Asymptomatic or pauci-symptomatic Ebola infections in contact participants (virological assessment)	Presence of Ebola virus identified by PCR in biological samples (blood, urine, feces, saliva, tears, breast milk (breastfeeding women), genital secretions and sperm (men aged 15 and over)).	Baseline (BL)
Primary	Evolution over time of peripheral blood mononuclear cells (PBMC) in cured and contact participants (cellular immunological sub-study)	Phenotypic characterization and activation status of the different cell populations within PBMC (T cells, B cells, natural killer cells, dendritic cells, etc.) by flow cytometry	Baseline (BL), month 6, month 12
Primary	Evolution over time of concentration of immune response analytes in cured and contact participants (cellular immunological sub-study)	Titration of analytes involved in immune responses (using Luminex technology)	Baseline (BL), month 6, month 12
Primary	Evolution over time of EBOV-specific T responses in cured and contact participants (cellular immunological sub-study)	EBOV-specific T responses after stimulation of cells by flow cytometry	Baseline (BL), month 6, month 12
Primary	Evolution over time of gene-expression profile in cured and contact participants (cellular immunological sub-study)	Analysis of gene-expression profile in whole blood using Ilumina technology	Baseline (BL), month 6, month 12
Primary	Evolution over time of genetic heterogeneity in cured and contact participants (cellular immunological sub-study)	Single-cell analysis to evaluate cellular genetic heterogeneity in cell population.	Baseline (BL), month 6, month 12
Primary	Genetic sub-study in cured and contact participants	Research of genetic variants implied in EBOV-infection response.	Baseline (BL)