Clinical trial NCT04033887: Evaluation Study of RDTs Detecting Antibodies Against HCV
Official title: Evaluation Study of Rapid Diagnostic Tests (RDTs) Detecting Antibodies Against Hepatitis C Virus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C
Keywords: Diagnosis
HIV coinfection
Rapid diagnostic test
Lead sponsor: Foundation for Innovative New Diagnostics, Switzerland
Sponsor class: OTHER
Collaborators: name: Institute of Tropical Medicine, Belgium
name: Nigerian Institute of Medical Research
name: Richard Lugar Centre for Public Health Research, Georgia
First posted: 2019-07-26
Enrollment: 1710
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Samples tested in Belgium originate from Cambodia (80%) and Belgium (20%). Cambodian samples are leftovers from samples collected during a cross-sectional study of hepatitis C among people living with HIV (De Weggheleire, A. 2017); samples in Belgium were collected and archived during routine patient care visits to the HIV clinic.

Samples in Nigeria originate from routine diagnostic activities at NIMR as well as the AIDS Prevention Initiative Nigeria (APIN) PEPFAR Program Sample/Data Bank setup at NIMR and the Lagos University Teaching Hospital.

Samples tested in Georgia are leftover samples from a previous FIND HCV study (Reipold, E.I., 2019), as well as archived routine diagnostic samples from the site.

Percent sample distribution per site:

Belgium: 38% Nigeria: 41% Georgia: 21%

Brief summary: The study aims to evaluate 13 different HCV RDTs (10 on-market, 3 under development) for their diagnostic performance and operational characteristics in archived EDTA plasma samples, originating from patients from different geographical regions (Nigeria, Georgia, Cambodia, Belgium) and with or without HIV co-infection.

Detailed description: Background and rationale:

Screening of past exposure to Hepatitis C Virus (HCV) infection is done by detection of HCV specific antibodies. In Low and Middle Income Countries (LMICs), where equipped laboratories and trained staff are limited, Rapid Diagnostic Tests (RDTs) are widely used for HCV screening. Although many RDTs are available on the market, only some of them received CE-IVD marking and only two have been validated by WHO Pre-Qualification (PQ). More quality-assured tests are needed to establish effective screening programmes in LMICs.

Furthermore, an important research gap is the lack of studies on the impact of HIV positivity on RDT performance, as it is estimated that 2-15% of people living with HIV are co-infected with HCV.

The evaluation of RDT performance on clinical samples collected in different geographic regions as well as from HIV co-infected individuals, would allow to identify tests with a performance meeting or having the potential to meet WHO quality standards.

Concept:

This is a multicenter laboratory evaluation study using archived, frozen plasma samples.

Sensitivity and specificity of RDTs will be measured against a composite reference standard that consists of two WHO prequalified Enzyme Immunoassays (EIAs) (Murex Anti-HCV EIA version 4.0, Fujirebio Innotest HCV Ab IV) and a Line Immunoassay (LIA) (MP Diagnostics HCV blot 3.0). Samples are assigned as anti-HCV negative or anti-HCV positive based on the results of all three assays.

RDT results will be read by three independent readers to evaluate inter-reader variability (differences in visual interpretation, i.e. presence or absence of test and control line).

For each RDT, two independently produced lots will be tested for each sample to assess lot-to-lot variability (differences in RDT result for the same sample). Furthermore, rate of invalid runs will be assessed and a technical appraisal is completed for each RDT.

Primary objective:

1.1 Evaluation of sensitivity and specificity of anti-HCV RDTs in archived plasma samples, collected from HCV-infected and HCV-uninfected individuals not co-infected with HIV, measured against the composite reference standard composed of two Enzyme Immunoassays (EIAs) and a Line Immunoassay (LIA).

1.2 Evaluation of sensitivity and specificity of anti-HCV RDTs in archived plasma samples, collected from HCV-infected and HCV-uninfected individuals who are all co-infected with HIV, measured against the composite reference standard composed of two EIAs and a LIA.

Secondary objectives:

2.1 Evaluation of sensitivity and specificity of anti-HCV RDTs in archived plasma samples, collected from HCV-infected and HCV-uninfected individuals, both co-infected and not with HIV, measured against the composite reference standard composed of two EIAs and a LIA.

2.2 Evaluation of operational characteristics of anti-HCV RDTs: inter-reader variability; lot-to-lot variability; rate of invalid runs 2.3 Technical appraisal of each RDT product per manufacturer

Eligibility criteria: Inclusion Criteria of archived samples:

* Non-hemolytic plasma samples with EDTA used as anticoagulant
* Sample were frozen at -20°C or lower on the day of processing and stored at -20°C or lower until they are used in this study
* Samples pre-characterized for, HCV, HIV serology status using assays routinely used at the sites and approved for diagnostic use by a local health authority. If available, samples should also be characterized for HBV status.
* Samples taken from subjects aged ≥18 years
* Availability of informed consent to use the sample in future research

Exclusion Criteria:

- Samples not stored correctly

Primary outcomes:
measure: Point estimates of sensitivity and specificity, with 95% confidence intervals, of RDTs for the detection of anti-HCV antibodies in individuals not co-infected with HIV.
timeFrame: 6 months
measure: Point estimates of sensitivity and specificity, with 95% confidence intervals, of RDTs for the detection of anti-HCV antibodies in HIV co-infected individuals.
timeFrame: 6 months
Secondary outcomes:
measure: Point estimates of sensitivity and specificity, with 95% confidence intervals, of RDTs for the detection of anti-HCV antibodies in the overall sample population.
timeFrame: 6 months
measure: Operational characteristics
timeFrame: 6 months
measure: Technical appraisal rating on kit instructions, packaging, labelling and test conduct, on a Likert scale
timeFrame: 6 months
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Institute of Tropical Medicine
city: Tbilisi
country: Georgia
facility: National Center for Disease Control & Public Health/Lugar Center
city: Lagos
country: Nigeria
facility: Nigerian Institute of Medical Research
Study officials:
affiliation: Foundation for Innovative New Diagnostics, Geneva, Switzerland
name: Ranga Sampath, PhD
role: STUDY_DIRECTOR
affiliation: Nigerian Institute of Medical Research, Lagos, Nigeria
name: Rosemary Audu, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Tropical Medicine, Antwerp, Belgium
name: Katrien Fransen, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: NCDC Lugar Centre, Tbilisi, Georgia
name: Maia Alkhazashvili, Masters
role: PRINCIPAL_INVESTIGATOR
References:
citation: De Weggheleire A, An S, De Baetselier I, Soeung P, Keath H, So V, Ros S, Teav S, Smekens B, Buyze J, Florence E, van Griensven J, Thai S, Francque S, Lynen L. A cross-sectional study of hepatitis C among people living with HIV in Cambodia: Prevalence, risk factors, and potential for targeted screening. PLoS One. 2017 Aug 23;12(8):e0183530. doi: 10.1371/journal.pone.0183530. eCollection 2017.
citation: Reipold, E.I., Evaluation of the diagnostic performance of the Xpert® Fingerstick HCV Viral Load (VL) Assay. Manuscript in preparation 2019
citation: Vetter BN, Reipold EI, Ongarello S, Audu R, Ige FA, Alkhazashvili M, Chitadze N, Vanroye F, De Weggheleire A, An S, Fransen K. Sensitivity and Specificity of Rapid Diagnostic Tests for Hepatitis C Virus With or Without HIV Coinfection: A Multicentre Laboratory Evaluation Study. J Infect Dis. 2022 Aug 26;226(3):420-430. doi: 10.1093/infdis/jiaa389.