Hepatitis B Virus (HBV), HEPATITIS C (HCV), HIV - Human Immunodeficiency Virus
Conditions
Keywords
Hepatitis C, Hepatitis B, HIV, CREST
Brief summary
This is a two-arm cluster randomized control trial to evaluate the effectiveness of a single-visit point-of-care (POC) test and treat bundle (intervention arm) compared to the current standard-of-care (SOC, control arm). 1:1 randomization occurs at the site level.
Interventions
DEVICECepheid GeneXpert HCV Test
Cepheid Xpert HCV Test, performed on the GeneXpert Xpress system, in an automated in vitro reverse transcription polymerase chain reaction (RT-PCR) test for the qualitative detection of Hep C (HCV) RNA in human fingerstick.
DEVICEAbbott Determine HIV - 1/2 Ag/Ab
Abbott Determine HIV - 1/2 Ag/Ab combo is an in vitro, visually read, qualitative immunoassay for the simultaneous detection of Human Immunodeficiency Virus type-1 (HIV-1) p24 antigen (Ag) and antibodies (Ab) to HIV type-1 and type-2 in fingerstick. Intended use is point-of-care test to aid in the diagnosis of infection.
DEVICEAbbott Determine HbsAg 2
Determine HBsAg 2 is an in vitro, visually read, qualitative immunoassay for detection of Hepatitis B Surface Antigen (HBsAg) in human fingerstick. The test is intended as an aid to detect HBAg from infected individuals.
Participants with detectable HCV RNA on Xpert test will receive sofosbuvir/velpatasvir at the same visit as the POC test in the intervention arm. Participants in the SOC arm will receive sofosbuvir/velpatasvir after standard of care testing and treatment assessment has been completed.
Sponsors
Duke University
Yale University
West Virginia University
University of San Diego
Cepheid
Gilead Sciences
Abbott
National Institute of Allergy and Infectious Diseases (NIAID)
Flinders University International Centre for Point-of-care Testing
Kirby Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Can provide written informed consent or assent 2. Minimum of 16 years of age 3. Willing to undergo HIV, HCV, HBV testing 4. Willing to undergo treatment for HCV and complete study activities
Exclusion criteria
1. History of HCV treatment for current infection 2. Known preexisting (evidence or history of) decompensated liver disease based on: medical diagnosis through medical record, reporting by the participant, or clinical evidence per the site PI 3. Contraindication for treatment with sofosbuvir/velpatasvir due to allergy or drug-drug interaction including use of any prohibited concomitant medications within 28 days prior to study entry. 4. History of clinically significant illness or any other major medical disorder that may interfere with participant treatment, assessment, or compliance with study requirements as determined by the site PI 5. Ongoing need for use of daily proton pump inhibitor (PPI) at doses ≥40 mg of omeprazole (or equivalent). NOTE: PPI can be discontinued or dose reduced to 20 mg/day of omeprazole (or equivalent) at time of study entry. Retreatment Inclusion Criteria: 1. Completion of sofosbuvir/velpatasvir treatment regimen as enrolled participant in CREST and willingness to receive retreatment. FIB-4 \& CTP score available within 90-days of retreatment initiation. 2. Meeting any of the below criteria during post-cessation treatment follow-up. Relapse, defined as HCV RNA \<LLOQ/D (TD or TND) during and/or at end of treatment followed by HCV RNA \>LLOQ/D or target detected based on qualitative POC test at any time point from end of treatment to 12 weeks after end of treatment OR Re-infection, defined as meeting the primary outcome criteria for SVR4+ followed by HCV RNA \>LLOQ/D or target detected based on qualitative POC test at any time point beyond meeting SVR4+ OR Post-treatment virologic failure, defined as HCV RNA \>LLOQ/D at any point after end of treatment (after week 24 visit) or during follow-up, not otherwise meeting definition of relapse or re-infection Retreatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who complete the Hepatitis C Virus (HCV) care cascade within 24 weeks of study entry in intervention versus Standard of Care (SOC) arm. | 24 weeks from study enrollment | Proportion of participants in the primary analysis population (as defined as detectable HCV RNA on dried blood spot testing at screening) who complete the HCV care cascade within 24 weeks of study entry in intervention versus SOC arm. Completion of the care cascade will be defined as HCV RNA\<lower limit of quantification/detection (LLOQ/D) at a minimum of 4 weeks post-cessation of direct-acting antiviral (DAA) therapy sustained virologic response (SVR4+). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants initiating same-visit direct-acting antiviral (DAA) treatment following enrollment (intervention arm only) | Day 1 | Proportion of participants initiating same-visit DAA treatment following enrollment (intervention arm only) |
| Proportion of participants initiating direct-acting antiviral (DAA) therapy within 12 weeks of entry | 12 weeks | HCV related outcomes are assessed in the primary analysis population (as defined by entry dried blood spot testing at screening) and compared between intervention and SOC arms. |
| Proportion of participants initiating direct-acting antiviral (DAA) therapy within 24 weeks of entry | 24 | HCV related \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
| Time from enrollment to treatment initiation | up to 24 weeks | HCV related \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
| Proportion of participants completing direct-acting antiviral (DAA) therapy within 24 weeks of entry | 24 weeks | HCV related outcomes are assessed in the primary analysis population (as defined by entry dried blood spot testing at screening) and compared between intervention and SOC arms. |
| Proportion of participants achieving sustained virologic response (SVR4+) within 60 weeks of entry | 60 weeks | HCV related outcomes are assessed in the primary analysis population (as defined by entry dried blood spot testing at screening) and compared between intervention and SOC arms. |
| Cumulative incidence of HCV reinfection following sustained virologic response (SVR4+) within 60 weeks of entry | within 60 weeks | HCV related outcomes are assessed in the primary analysis population (as defined by entry dried blood spot testing at screening) and compared between intervention and SOC arms. |
| Cumulative retreatment following sustained virologic response (SVR4+) or relapse within 60 weeks of entry | within 60 weeks | HCV related \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. This analysis for retreatment is limited to participants 18 years old and older. |
| Proportion of participants with HCV RNA not detected based on dried blood spot at week 24 and week 60 | Week 24 and 60 | HCV related \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
| Proportion of participants who have received any HIV test result within 24 weeks of entry | 24 weeks of entry | HIV related outcomes are assessed in the primary analysis population (as defined by entry dried blood spot testing at screening) and compared between intervention and SOC arms. |
| Proportion of participants who initiate PrEP within 24 weeks of entry | 24 weeks of entry | HIV related outcomes are assessed in the primary analysis population (as defined by entry dried blood spot testing at screening) and compared between intervention and SOC arms. |
| Proportion of participants with HIV who commence direct-acting antiviral (DAA) therapy within 24 weeks of entry | 24 weeks of entry | HIV related outcomes are assessed in the primary analysis population (as defined by entry dried blood spot testing at screening) and compared between intervention and SOC arms. |
| Proportion of participants with HIV not on antiretroviral therapy (ART) at screening who commence ART within 24 weeks of entry | 24 weeks of entry | HIV related outcomes are assessed in the primary analysis population (as defined by entry dried blood spot testing at screening) and compared between intervention and SOC arms. |
| Proportion of participants with HIV on antiretroviral therapy (ART) at screening who remain on ART at week 24 and week 60 | Week 24 and 60 | HIV related \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
| Time from enrollment to PrEP initiation | up to 60 weeks | HIV related \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
| All cause and liver specific hospitalizations through week 60 | 60 weeks | Safety \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
| All cause and liver specific mortality through week 60 | Week 60 | Safety \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
| On direct-acting antiviral (DAA) treatment serious suspected adverse events leading to discontinuation of sofosbuvir/velpatasvir | 60 weeks | Safety \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
| Adverse maternal and fetal outcomes for those on direct-acting antiviral (DAA) at any time during pregnancy | up to 60 weeks | Safety \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
| Adverse device effects related to study devices | up to 60 weeks | Safety \[all outcomes are assessed in the primary analysis population (as defined by dried blood spot testing at screening) and compared between intervention and SOC arms\]. |
Contacts
PRINCIPAL_INVESTIGATORSusanna Naggie, MD, MHS
Duke University
Outcome results
None listed