MIGrant Reflex Test HDV (MIGRED) Project

NCT ID: NCT06539052

Last Updated: 2024-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

7500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-12-20

Study Completion Date

2026-12-20

Brief Summary

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Our research team has executed a robust strategy to improve viral hepatitis detection and linkage to care in migrants, contributing to the improvement of knowledge on the clinical and virological future of viral hepatitis in this population difficult to reach and manage. Our hypothesis is that the extension of our model to three other large university clinical centers operating in southern Italy and the use of HDV reflex testing for HBsAg-positive subjects will allow the implementation of knowledge on prevalence of HDV in migrants living in southern Italy and coming from HDV endemic areas. Precisely, the investigators will involve the Department of Infectious Diseases of the University of Bari, that of the University of Catanzaro and that of the University of Palermo with expertise in the management of infectious diseases in the migratory context and with whom the investigators have previously collaborated in other areas.

It is expected to enroll at least 7500 patients. The project will last 18 months.

Diagnosis and treatment of HDV infection in migrants will reduce the circulation of HDV in low endemic regions such as our region. Follow-up of HDV-infected individuals and reducing the rate of new infections among migrants will reduce the number of people who will experience complications related to HDV infection, such as decompensated liver cirrhosis and carcinoma hepatocellular. All this will determine benefits for the Italian public health system.

Detailed Description

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Hepatitis D virus (HDV) infection, which occurs only in subjects with hepatitis B infection, increases the risk of hepatocellular carcinoma (HCC), decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) mono-infection. Therefore, estimates the prevalence of HDV infection and disease burden are essential to investigate models to find coinfected individuals more effectively and in an efficient way. Diagnosis of HDV allows to reduce the risk of disease progression and prevent HDV transmission, allows to intervene with antiviral treatment and allows to follow-up HDV positive subjects with ultrasound for HCC surveillance \[1-4\]. The data on the prevalence of HDV worldwide is unclear, with an estimated prevalence of anti-Delta-positivity in HBsAg positive patients of 4.5%-13% and an estimated number of anti-Delta-subjects of 8,2-60 million \[5-6\]. These variable estimates may be due in part to the fact that not all HBsAg-positive subjects were screened for anti-Delta. All the strategies for the improvement of the rate of screening of HBsAg-positive-subjects may improve the knowledge on the prevalence of HDV worldwide, especially in the high endemic populations. Recently, one of the strategies that has shown good results in the identification of HDV infection is the use of anti HDV reflex testing \[4\]. However, HDV is highly endemic in several African countries and in some countries in South America, the Middle East, central and northern Asia, and Eastern Europe \[7\]. A systematic review of the prevalence of HDV infection in HBsAgpositive populations in sub Saharan Africa showed a pooled seroprevalence in HBsAg-positive general populations and in patients with liver disease of 7.33% and 9.57%, respectively in western Africa, of 25.6% and 37.8% in central Africa, and of 0.05% in the general populations of eastern and southern Africa \[8\]. In Italy the prevalence of HDV infection in HBsAg-positive subjects ranges from 9.7 to 12%, with evidence of an increasing prevalence of HDV infection in the immigrant population in recent years \[9-15\]. Probably, this happened because for its geographical position in the center of the Mediterranean Sea, Italy has been greatly involved in immigration from Africa, in particular from sub-Saharan Africa, and also from Asia and Eastern Europe; for example from January 2023 until September 2023 in Italy are arrived about 128,000 migrants and most of them coming from Sub-Saharan Africa and East Europe, prevalence (Situation Mediterranean Situation (unhcr.org), all areas with high HDV prevalence, The majority of these migrants arrived, as first site, in Southern Italy, Sicily, Apulia, Calabria and Campania. However, few data have been published so far on the prevalence of HDV infection in immigrant populations in Western countries and in Italy and even poorer is the information on the virological and clinical aspects of HDV infection in this population.

Our research group performed a valid strategy to improve the detection for viral hepatitis and the link to care in migrants, contributing to the improvement of knowledge on clinical and virological futures of viral hepatitis in this population difficult to reach and to manage \[1-3\]. Our hypothesis is that the extension of our model in other three large university clinical centers operating in southern Italy and the use of the HDV reflex testing for HBsAg-positive individuals will allow to implement the knowledge on the HDV prevalence in migrants living in southern Italy and coming from endemic areas for HDV. Precisely, the investigators will involve the Department of Infectious Diseases of the University of Bari, that of the University of Catanzaro and that of the University of Palermo with expertise in the management of infectious diseases in migrant and with which the investigators previously collaborated in other setting.The investigators performed a retrospective and prospective multicenter project lasting 18 months involving the 4 largest University clinical Centers for Infectious Diseases (ID) in southern Italy:

Departments of ID of the University of Napoli L.Vanvitelli (project coordinator), of the University of Bari, of the University of Catanzaro and of the University Palermo.

At this time they are not involved in any other projects involving screening and linkage to care of HDV infection.

Each of these tertiary center is associated to 1st level clinical centers, that are centers of general practice clinics attended mainly by migrants for low back pain, headache, itching, cough, hypertension and allergy symptoms. These first-level centers are linked with the Italian humanitarian organizations which welcome needy migrants. The organization of these clinics involves the presence of a physhycian expert in the management of infectious diseases in migrants, a nurse and a cultural mediator. This last figure is fundamental in explaining the epidemiological, clinical and collective health reasons that make it necessary to screen for hepatitis viruses which are endemic in their areas of origin.

Screening process All sample of migrants relating to the infectious diseases clinic of the centers participating in the project will be collected.

To improve the rate of enrollment, the physicians, with the help of cultural mediators, will explain to the what are the main sexually and parenterally transmitted infectious diseases endemic in their countries of origin and will be information on the routes of transmission of theses. The information/education will be done through brochures with pictures and explanations translated into English, French and Swahili. The migrants, who agreed to join the project, signed an informed consent written in the immigrant's own language and filled out an anonymous questionnaire administered by the research investigators with the assistance of a cultural mediator on the demographic data, date of immigration, socioeconomic status (level of education), religion, cohabitation details, sexual orientation and practices including condom use, history of HBV vaccination, surgery, dental care, tattooing, body piercing, use of drugs, blood transfusion, tribal rituals, abortion and information on previously documented personal and family infections of HBV, HDV, HCV and HIV. The data relating to the epidemiological characteristics will collected in an electronic database.

A blood sample will be collected. The cultural mediator will support the clinicians and the nurses who will collect the blood sample to ensure that the migrant fully and freely understands the reasons of the screening.

An epidemiological data sheet will be associated with the blood sample. Every center will carry out HBsAg testing on the blood samples collected. The HBsAg positivity will be the trigger to start the HDV reflex testing cascade: in the same blood sample testing positive for HBsAg, anti-HDV will be tested; in cases of anti-HDV positivity the same serum sample will be collected to test HDV RNA.

HDV RNA will be performed at the molecular biology laboratory of the Department of ID of the University of Naples (project coordinator) according to standard methods. Once a month, the samples tested anti-HDV positive with the reflex testing methodology will be carried on dry ice at a controlled temperature to the reference center for the virological tests. For subjects with positive HDV viremia the investigators will proceed for HDV genotyping on the same serum sample.

The same sample will also be tested for HIV and HCV, any positivity will be communicated to the reference.

All HBsAg-positive subjects will be linked to the tertiary centers. The cultural mediator will accompany the migrants testing positive to the screening to stage the liver disease and to start the therapeutic management of subjects with HBV infection and HBV HDV co-infection according to international guidelines.

In the Retrospective phase of the project about 2000 stored samples of migrant enrolled in a previous study will be re-tested for HBsAG, HCV Ab and HIV ab. In the same blood sample testing positive for HBsAg, anti-HDV will be tested; in cases of anti-HDV positivity the same serum sample will be collected to test HDV RNA.

In the regions of southern Italy where the project will take place, that is Campania, Apulia, Calabria and Sicily, approximately 128,000 migrants arrived from January 2023 until September 2023 (https://data2.unhcr.org/en/situations/mediterranean). In consideration of the economic availability of the project the investigators aim to evaluate approximately 7,500 migrants. the investigators hypothesize to enroll 7500 migrants. Of these 7500, the investigators hypothesize that about 4500 have already been screened for HBsAg, HCV Ab, HIV Ab, while 3000 must been screened for these viruses. The project will last 18 months and for all 7500 enrolled migrants will be carried out HBsAg, HIV Ab and HCV Ab screening. Samples positive for HBsAg will be tested for HDV at the same time as the positive result of HBsAg. Considering a prevalence of HBsAg-positivity of 10% in migrant population, the investigators hypothesize to identify 750 HBsAg-positive subjects. Considering that the prevalence of HDV in HBsAg positive subjects in Africa is estimated of approximately 9%, the investigators hypothesize to identify 68 anti-HDV positive subjects.

Conditions

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Hepatitis D Virus Infection

Study Design

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Observational Model Type

OTHER

Study Time Perspective

OTHER

Study Groups

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migrants

All migrants, documents or undocumented migrants, and low-income refugees belonging to the infectious disease centers of the university centers participating in the project will be enrolled.

All HBsAg-positive subjects will be linked to the tertiary centers. The cultural mediator will accompany the migrants testing positive to the screening to stage the liver disease and to start the therapeutic management of subjects with HBV infection and HBV HDV co-infection according to international guidelines.

In the Retrospective phase of the project about 2000 stored samples of migrant enrolled in a previous study will be re-tested for HBsAG, HCV Ab and HIV ab. In the same blood sample testing positive for HBsAg, anti-HDV will be tested; in cases of anti-HDV positivity the same serum sample will be collected to test HDV RNA.

anti-HDV positive with the reflex testing methodology

Intervention Type DIAGNOSTIC_TEST

Rate of screening for HBsAg in all migrants attending to one of the center participating to the project rate of screening for anti-Delta in all HBsAg patients identified rate of anti-Delta-positivity in HBsAg-positive subjects rate of linkage-to-care at one of the infectious disease center participating to the project rate of HDV-RNA testing in all anti-Delta positive subjects rate of treatment for HDV in all HDV-RNA-positive subjects Rate of screening for HIV Ab in all migrants attending to one of the center participating to the project Rate of screening for HCV Ab in all migrants attending to one of the center participating to the project.

Interventions

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anti-HDV positive with the reflex testing methodology

Rate of screening for HBsAg in all migrants attending to one of the center participating to the project rate of screening for anti-Delta in all HBsAg patients identified rate of anti-Delta-positivity in HBsAg-positive subjects rate of linkage-to-care at one of the infectious disease center participating to the project rate of HDV-RNA testing in all anti-Delta positive subjects rate of treatment for HDV in all HDV-RNA-positive subjects Rate of screening for HIV Ab in all migrants attending to one of the center participating to the project Rate of screening for HCV Ab in all migrants attending to one of the center participating to the project.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* All migrants, documents or undocumented migrants, and low-income refugees belonging to the infectious disease centers of the university centers participating in the project will be enrolled. aged \> 18 years subjects who have given informed consent to carry out blood sampling and for the collection of epidemiological data

Exclusion Criteria

* all migrants \< 18 years of age who have not given informed consent for the collection of the blood sample and/or epidemiological data.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role lead

Responsible Party

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Nicola Coppola

Chief of Infectoius Diseases Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nicola Coppola, MD

Role: PRINCIPAL_INVESTIGATOR

Università della Campania Luigi Vanvitelli

Central Contacts

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Nicola Coppola, MD

Role: CONTACT

Phone: +390815666223

Email: [email protected]

Laura Occhiello, SC

Role: CONTACT

Phone: +390815666223

Email: [email protected]

References

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Other Identifiers

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MIGRED

Identifier Type: -

Identifier Source: org_study_id