Combating Related Epidemics in HCV

Official title

Combating Related Epidemics in HCV Through Simplified Testing and Treatment. A Cluster Randomized Trial of Point-of-care Hepatitis C Testing and Treatment Among Key Populations

Overview

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

• Device Cepheid 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.
• Device Abbott 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.
• Device Abbott 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.
• Drug Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]
  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.

Primary outcome measures

• 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. [Time frame: 24 weeks from study enrollment]

Secondary outcome measures (12)

• Proportion of participants initiating same-visit direct-acting antiviral (DAA) treatment following enrollment (intervention arm only) [Time frame: Day 1]
• Proportion of participants initiating direct-acting antiviral (DAA) therapy within 12 weeks of entry [Time frame: 12 weeks]
• Proportion of participants initiating direct-acting antiviral (DAA) therapy within 24 weeks of entry [Time frame: 24]
• Time from enrollment to treatment initiation [Time frame: up to 24 weeks]
• Proportion of participants completing direct-acting antiviral (DAA) therapy within 24 weeks of entry [Time frame: 24 weeks]
• Proportion of participants achieving sustained virologic response (SVR4+) within 60 weeks of entry [Time frame: 60 weeks]
• Cumulative incidence of HCV reinfection following sustained virologic response (SVR4+) within 60 weeks of entry [Time frame: within 60 weeks]
• Cumulative retreatment following sustained virologic response (SVR4+) or relapse within 60 weeks of entry [Time frame: within 60 weeks]
• Proportion of participants with HCV RNA not detected based on dried blood spot at week 24 and week 60 [Time frame: Week 24 and 60]
• Proportion of participants who have received any HIV test result within 24 weeks of entry [Time frame: 24 weeks of entry]
• Proportion of participants who initiate PrEP within 24 weeks of entry [Time frame: 24 weeks of entry]
• Proportion of participants with HIV who commence direct-acting antiviral (DAA) therapy within 24 weeks of entry [Time frame: 24 weeks of entry]

Eligibility criteria

Inclusion criteria

• Can provide written informed consent or assent
• Minimum of 16 years of age
• Willing to undergo HIV, HCV, HBV testing
• Willing to undergo treatment for HCV and complete study activities

Exclusion criteria

• History of HCV treatment for current infection
• 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
• 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.
• 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
• 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:

• 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.
• 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 Exclusion Criteria:

• Known preexisting (evidence or history of) decompensated liver disease based on: medical diagnosis through medical record, reporting by the participant, clinical evidence per the site PI, or by CTP score ≥7.
• Pregnant or breast feeding at time of retreatment with sofosbuvir/velpatasvir/voxilaprevir.
• Contraindication for treatment with sofosbuvir/velpatasvir (reinfection) or sofosbuvir/velpatasvir/voxilaprevir (relapse or virologic failure) due to FDA package insert, allergy, or drug-drug interaction including use of any prohibited concomitant medications within 28 days prior to study entry.
• 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
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Solomon SS, Wagner-Cardoso S, Smeaton L, Sowah LA, Wimbish C, Robbins G, Brates I, Scello C, Son A, Avihingsanon A, Linas B, Anthony D, Nunes EP, Kliemann DA, Supparatpinyo K, Kityo C, Tebas P, Bennet JA, Santana-Bagur J, Benson CA, Van Schalkwyk M, Cheinquer N, Naggie S, Wyles D, Sulkowski M. A minimal monitoring approach for the treatment of hepatitis C virus infection (ACTG A5360 [MINMON]): a p PMID 35026142
• Sheehan Y, Cunningham EB, Cochrane A, Byrne M, Brown T, McGrath C, Lafferty L, Tedla N, Dore GJ, Lloyd AR, Grebely J. A 'one-stop-shop' point-of-care hepatitis C RNA testing intervention to enhance treatment uptake in a reception prison: The PIVOT study. J Hepatol. 2023 Sep;79(3):635-644. doi: 10.1016/j.jhep.2023.04.019. Epub 2023 Apr 26. PMID 37116714
• Coyle C, Moorman AC, Bartholomew T, Klein G, Kwakwa H, Mehta SH, Holtzman D. The Hepatitis C Virus Care Continuum: Linkage to Hepatitis C Virus Care and Treatment Among Patients at an Urban Health Network, Philadelphia, PA. Hepatology. 2019 Aug;70(2):476-486. doi: 10.1002/hep.30501. Epub 2019 Mar 26. PMID 30633811
• Mahase E. Hepatitis C: Egypt makes "unprecedented progress" towards elimination. BMJ. 2023 Oct 10;383:2353. doi: 10.1136/bmj.p2353. No abstract available. PMID 37816531
• Dore GJ. Elimination of hepatitis C in Australia by 2030: a decade and counting. Aust Prescr. 2021 Apr;44(2):36-37. doi: 10.18773/austprescr.2021.003. Epub 2021 Apr 1. No abstract available. PMID 33911328
• Eckhardt B, Mateu-Gelabert P, Aponte-Melendez Y, Fong C, Kapadia S, Smith M, Edlin BR, Marks KM. Accessible Hepatitis C Care for People Who Inject Drugs: A Randomized Clinical Trial. JAMA Intern Med. 2022 May 1;182(5):494-502. doi: 10.1001/jamainternmed.2022.0170. PMID 35285851
• Eckhardt B, Kapadia SN, Mateu-Gelabert P, Pai M, Fong C, Aponte-Melendez Y, Marks KM. Rapid Treatment Initiation for Hepatitis C in Young People Who Inject Drugs: The Seek, Test, and Rapid Treatment Randomized Trial. Open Forum Infect Dis. 2022 May 7;9(7):ofac225. doi: 10.1093/ofid/ofac225. eCollection 2022 Jul. PMID 35821731
• Brooks R, Wegener M, Freeman B, Fowles C, Madden LM, Tetrault JM, Nichols L, Altice FL, Villanueva M. Improving HIV and HCV Testing in Substance Use Disorder Programs (SUDs) That Provide Medications for Opiate Use Disorder (MOUD): Role of Addressing Barriers and Implementing Universal and Site-Specific Approaches. Health Promot Pract. 2023 Sep;24(5):1018-1028. doi: 10.1177/15248399231169791. Epub PMID 37439759

Identifiers

NCT: NCT07560046 · Pro00118863 · 1U01AI195193

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗