Evaluation of Dried Blood Spot for HCV RNA Testing

Study Overview
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Brief Summary
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FIND is preparing a study to evaluate the performance, as measured by sensitivity and specificity, of four centralized assays for the detection of HCV RNA using capillary blood collected on dried blood spots (DBS) and plasma separation card (PSC).

Detailed Description
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Available data on the performance of HCV RNA assays from DBS samples are insufficient to introduce their use in clinical practice. Only a few studies have been performed on DBS stored at ambient temperature, while the majority had DBS samples refrigerated or frozen right after collection, which does not mimic real-life settings. Additionally, due to the lack of standardized procedures, DBS collection and elution protocols varied across different studies. A large multicentre diagnostic accuracy study using standardized DBS collection and elution protocols validated by test manufacturers is needed to inform national hepatitis programmes and international guideline development groups. Test manufacturers need clinical evaluation data to update their regulatory claims and include DBS as an alternative sample type. FIND is preparing a trial to evaluate the performance, as measured by sensitivity and specificity, of four laboratory-based assays for detection of HCV RNA assays using capillary blood collected on DBS/PSC. This will be provisional on the manufacturers agreeing to participate, as well as committing to applying to stringent regulatory approval for DBS/PSC.

Official Title
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Multicentre Clinical Trial to Assess the Performance of Centralized Assays for Hepatitis C Virus RNA Detection From Dried Blood Spot (DBS) Samples

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Diagnostic Test: Abbott RealTime HCV assay from DBS
* Diagnostic Test: HCV for use on the cobas® 6800/8800 Systems from PSC and DBS
* Diagnostic Test: Aptima® HCV Quant Dx Assay from DBS
* Diagnostic Test: HCV for use on the cobas® 4800Systems from PSC and DBS


Participation Criteria
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Eligibility Criteria
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Three different population groups will be considered: Individuals at risk of having HCV infection based on positive HCV serology test results Inclusion criteria: Aged 18 years or older Able to understand the scope of the trial Provided written informed consent Documented positive result of HCV serology test Individuals at risk of having HCV infection based on past and/or current exposure to risk factors Inclusion criteria: Aged 18 years or older Able to understand the scope of the trial Provided written informed consent Past and/or current exposure to one of the high risk factors as defined by WHO and CDC guidelines (Appendix I) Individuals diagnosed with chronic HCV infection who initiated or completed the anti-HCV treatment with direct acting antivirals (DAA) presenting at the clinical site for treatment monitoring or test of cure (i.e. sustained virological response) Inclusion criteria: Aged 18 years or older Able to understand the scope of the trial Provided written informed consent Initiated on DAA treatment (regardless of type of DAA regimen) within 12 months prior to the enrolment to the trial Exclusion criteria (for all trial populations): Previously enrolled in the trial Unwilling to provide required volume of fingerstick blood Unwilling to provide required volume of venous whole blood

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: clinical performance of the HCV DBS assay<br>The study will be conducted in different geographical regions and populations and is designed to meet requirements of the for assays (medical devices) used for the qualitative and quantitative detection of Hepatitis C RNA. | Diagnostic Test: Abbott RealTime HCV assay from DBS<br>* The trial intervention will consist of testing DBS, PSC and plasma samples obtained from trial participants using the centralised molecular assays for detection of HCV RNA. Results of testing DBS samples on the HCV assay will not be used to make any clinical decisions, and should not be communicated to study participants.<br>Diagnostic Test: HCV for use on the cobas® 6800/8800 Systems from PSC and DBS<br>* The trial intervention will consist of testing DBS, PSC and plasma samples obtained from trial participants using the centralised molecular assays cobas® 6800/8800 Systems for detection of HCV RNA. Results of testing DBS samples on the HCV assay will not be used to make any clinical decisions, and should not be communicated to study participants.<br>Diagnostic Test: Aptima® HCV Quant Dx Assay from DBS<br>* The trial intervention will consist of testing DBS, PSC and plasma samples obtained from trial participants using the centralised molecular assays Aptima® HCV Quant Dx Assay from DBS for detection of HCV RNA. Results of testing DBS samples on the HCV assay will not be used to make any clinical decisions, and should not be communicated to study participants.<br>Diagnostic Test: HCV for use on the cobas® 4800Systems from PSC and DBS<br>* The trial intervention will consist of testing DBS, PSC and plasma samples obtained from trial participants using the centralised molecular assays cobas® 4800 for detection of HCV RNA. Results of testing DBS samples on the HCV assay will not be used to make any clinical decisions, and should not be communicated to study participants.<br>|
| Active Comparator: comparison PQ marked reference assay arm<br>Plasma specimens from the participants will be tested on Abbott RealTime HCV assay that is approved for HCV diagnostics use by countries' authorities. | Diagnostic Test: Abbott RealTime HCV assay from DBS<br>* The trial intervention will consist of testing DBS, PSC and plasma samples obtained from trial participants using the centralised molecular assays for detection of HCV RNA. Results of testing DBS samples on the HCV assay will not be used to make any clinical decisions, and should not be communicated to study participants.<br>Diagnostic Test: HCV for use on the cobas® 6800/8800 Systems from PSC and DBS<br>* The trial intervention will consist of testing DBS, PSC and plasma samples obtained from trial participants using the centralised molecular assays cobas® 6800/8800 Systems for detection of HCV RNA. Results of testing DBS samples on the HCV assay will not be used to make any clinical decisions, and should not be communicated to study participants.<br>Diagnostic Test: Aptima® HCV Quant Dx Assay from DBS<br>* The trial intervention will consist of testing DBS, PSC and plasma samples obtained from trial participants using the centralised molecular assays Aptima® HCV Quant Dx Assay from DBS for detection of HCV RNA. Results of testing DBS samples on the HCV assay will not be used to make any clinical decisions, and should not be communicated to study participants.<br>Diagnostic Test: HCV for use on the cobas® 4800Systems from PSC and DBS<br>* The trial intervention will consist of testing DBS, PSC and plasma samples obtained from trial participants using the centralised molecular assays cobas® 4800 for detection of HCV RNA. Results of testing DBS samples on the HCV assay will not be used to make any clinical decisions, and should not be communicated to study participants.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point estimates (with 95% confidence intervals) of sensitivity and specificity for each assay for HCV RNA detection from DBS and/or PSC specimens measured against Abbott RealTime HCV VL assay performed at the clinical site | Point estimates (with 95% confidence intervals) of sensitivity and specificity for each assay for HCV RNA detection from DBS and/or PSC specimens measured against Abbott RealTime HCV VL assay performed at the clinical site | day 1 - day 30 | 
| Evaluation of the correlation of HCV viral load level determined by each assay performed from DBS and/or PSC specimens with the HCV viral load level in plasma determined by Abbott RealTime HCV VL assay performed at the clinical site | Evaluation of the correlation of HCV viral load level determined by each assay performed | day 1 - day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point estimates (with 95% confidence intervals) of sensitivity and specificity for each assay for HCV RNA detection from DBS and/or PSC specimens measured against the performance of the same assay in plasma | Point estimates (with 95% confidence intervals) of sensitivity and specificity for each assay for HCV RNA detection from DBS and/or PSC specimens measured against the performance of the same assay in plasma | day 1 - day 30 | 
| Evaluation of the correlation of HCV viral load level determined by each assay performed from DBS and/or PSC specimens with the HCV RNA level in plasma determined by the same assay | Evaluation of the correlation of HCV viral load level determined by each assay performed from DBS and/or PSC specimens with the HCV RNA level in plasma determined by the same assay | day 1 - day 30 | 
| WHO technician's appraisal sheet completed by all operators performing investigational test | WHO technician's appraisal sheet completed by all operators performing investigational test | through study completion, an average of 1 year | 
| point estimates (with 95% confidence intervals) of sensitivity and specificity for each assay for HCV RNA detection in plasma measured against the performance of Roche cobas® 6800 HCV VL assay | For Central Laboratory only | day 7 - day 30 | 
| evaluation of the correlation of HCV RNA levels in plasma determined by each assay with HCV RNA levels in plasma determined by Roche cobas® 6800 HCV VL assay | For Central Laboratory only | day 7 - day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dried blood spots, plasma separation card, HCV RNA test