Simplified Antiviral Treatment Strategy for Hepatitis C in Ukraine

Study Overview
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Brief Summary
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The project will evaluate cost and treatment outcomes of a simplified Hepatitis C Virus (HCV) testing, treatment and care model integrated with HIV testing and treatment among key affected populations in Ukraine.

Detailed Description
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Affected populations will be screened for HCV and HIV and those HCV positive treated with direct with direct acting anti-HCV agents (DAAs), a fixed-dose combination of sofosbuvir/ledipasvir (SOF/LDV) for 12 weeks with or without weight-based ribavirin. Before and after completion of the treatment course viral load assessments will be undertaken using low-cost laboratory monitoring for comparison to standard HCV viral load measurement. Up 800 patients enrolled on treatment will be followed up at 4, 8, 12 and 24 weeks when Sustained Viral Response (SVR) will be determined. Safety monitoring will be undertaken at applicable visits for those on Ribavirin and all adverse events will be reported based on Good Clinical Practice (GCP). In addition to assessing cost outcomes, the project will assess HCV treatment efficacy in terms of SVR at 12 weeks after end of treatment ( defined as undetected HCV RNA or less than lower limit of detection), compare the cost of low cost viral assay platforms to standard of care, assess rates of ART initiation and virologic suppression of HIV-infected persons within the simplified HCV treatment model and impact of HIV co-infection in participants on the HCV treatment outcome of SVR12. The project will be conducted at 2 treatment sites in Kiev.

Official Title
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Demonstration Project on Assessment of Simplified Antiviral Treatment Strategy for Hepatitis C in Ukraine

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: Sofosbuvir/ledipasvir (SOF/LDV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability and willingness of participant to provide informed consent. Attribution to one of the key population groups: People Who Inject Drugs (PWID), medication assisted treatment (MAT) participants, Commercial Sex Workers (CSW) or Men Having Sex with Men (MSM). Documentation of attribution to one of the key population groups will be done through applying Case Reporting Form Risks Assessment and Substance Use and Alcohol Consumption. Additionally, medical record of substance use can be collected Men and women age 18 years. Active HCV infection as defined by detectable serum or plasma HCV RNA at any time prior to study entry. Documentation may be obtained from medical records if available. If no medical records on HCV infection are available, HCV infection must be confirmed by a detectable HCV RNA PCR prior to project entry. Allowed HCV treatment history: HCV treatment naïve defined as not having been previously treated for Hepatitis C infection with any medications approved for the treatment of HCV in any country. HCV treatment experienced with interferon with or without ribavirin only (no prior DAA treatment, although they will be followed). Hepatitis B status must be documented by hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb) testing. Participants with positive hepatitis B surface antigen (HBsAg+) must be on an active HBV regimen at study entry. HIV-1 infection status must be documented as either absent or present, as defined below: Absence of HIV-1 infection, as documented by rapid HIV test or HIV-1 enzyme immunoassay (ELISA) test kit, within 60 days prior to entry. OR Presence of HIV-1 infection, documented by rapid HIV test or HIV-1 ELISA test kit at any time prior to entry and confirmed by a second antibody test by a method other than the initial rapid HIV and/or ELISA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. OR HIV-1 infection confirmed by medical documentation as participant is registered in care at AIDS Center and receiving or preparing to initiate ARV treatment. Participants who are assigned to receive ribavirin as part of the treatment protocol must have haemoglobin ≥110 g/L For females of reproductive potential, a negative urine pregnancy test (urine -HCG with a sensitivity of <25 mIU/mL) within 48 hours prior to project entry must be documented. Male and female participants who are able to impregnate or become pregnant (ie, of reproductive potential) and are participating in sexual activity that could lead to pregnancy must agree to practice contraception/birth control as indicated below or agree to not participate in a conception process while on treatment with ribavirin through at least 12 weeks post-treatment. Note: Acceptable contraception/birth control for this project includes one of the following methods: condoms (male or female) with a spermicide diaphragm or cervical cap with spermicide hormonally impregnated intrauterine device (IUD) non-hormonally impregnated IUD in conjunction with spermicide Hormone-based therapy Exclusion Criteria Child-Pugh Score corresponding to Class B or C (decompensated cirrhosis). This requires assessment for encephalopathy and ascites, as well as measurement of serum bilirubin, albumin, and international normalized ratio (Prothrombin time). For Child's cirrhosis severity calculator on the following link can be used: http://www.hepatitisc.uw.edu/page/clinical-calculators/ctp . Patients with decompensated cirrhosis and advanced liver disease will not be included to the treatment program, but they will remain under observation and will receive medical care within routine medical practice of the healthcare facility in such clinical cases. Breastfeeding or pregnancy. Pregnant or breastfeeding woman will be documented and provided access to HCV treatment after resolution of pregnancy and breastfeeding. Known allergy/sensitivity or any hypersensitivity to components of drug(s) or their formulation. Active tuberculosis (TB) infection. Given the high TB prevalence in Ukraine, every candidate should be screened for TB signs/symptoms with further medical evaluation for active TB as indicated. In the case of proven active TB infection, the participant is ineligible for HCV treatment (due to the adverse drug interaction of SOF/LDV and rifampicin) but will be followed and offered enrolment when they complete treatment with rifampicin. Renal impairment defined as estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 or end-stage renal disease receiving dialysis as treatment with SOF/LDV is contraindicated (https://www.mdcalc.com/mdrd-gfr-equation). The participant may be rescreened if the renal function improves. Patients with worse renal impairment will not be treated but will be followed and will recive medical aid within routine medical practice of the healthcare facility where project is implemented Prior treatment with any HCV Direct Acting Agents (DAA).

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HCV infected patients<br>All HCV infected confirmed by HCV RNA, | Drug: Sofosbuvir/ledipasvir (SOF/LDV)<br>* SOF/LDV (400mg/90mg) orally once daily with or without food in the morning and will receive treatment for a duration of 12 weeks. In addition, Ribavirin weight-based (1000 mg for patients <75 kg and 1200 mg for those ≥75 kg) administered orally in two divided doses with food for Genotype 3 patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated cost of HCV screening per patient screened and per case identified and the cost per successfully treated patient for HCV mono-infected and co-infected participants | The average cost to the provider per patient achieving SVR-12 will be estimated, as will the average cost per other outcomes achieved, such as per patient screened and per patient remaining in care by other specified endpoints, stratified by HIV status and by any other important patient or site characteristics that are identified as drivers of cost. The investigators will also estimate the average cost to produce a successful outcome (SVR-12), which is the ratio of total costs for the intervention for the entire sample enrolled to the number of patients achieving the primary outcome. This latter estimate captures the costs incurred for patients who do not have successful outcomes and thus relates resource utilization to health outcomes. | Two years. This will be after data on Viral load response is complete. | 
| Sustained Viral Response | This will be the main treatment outcome of all patients initiated on treatment. Baseline viral load is done at entry with treatment initiated for those positive and eligible. Patients initiated on treatment will be assessed for viral load response at 24 weeks ( 12 weeks post treatment). This will also help in development of a Care cascade model for HCV testing, treatment and SVR12 in key populations co-infected with HIV/HCV, HIV/HCV/HBV, HBV/HCV and HCV mono-infected. | 24 weeks ( 12 weeks post treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV genotype | HCV genotype will be determined at entry for all patients. | At baseline | 
| HCV subtype | All genotypes will be subtyped once | Baseline | 
| Validity of Cepheid Gene-Xpert in monitoring SVR12 | 150 patients will be evaluated for HCV viral load at entry and exit comparing Cepheid Gen-Xpert and Real time PCR using Ampliscence platform. | Testing done and baseline and 24 weeks | 
| HIV viral load among HCV/HIV co-infected patients | HCV/HIV co-infected patients will be on treatment at the time of HCV treatment initiation but those not on ART will be initiated and will assess rates of ART initiation and virologic suppression of the HIV infected within the simplified HCV testing and treatment model | HIV Viral load at 24 weeks ( 12 weeks post HCV treatment) | 
| Reliability of Cepheid Gene-Xpert in monitoring SVR12 | Cepheid Gen-Xpert and Real time PCR using Ampliscence platform. | Testing done and baseline and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C Virus, HIV, Key Population