Simplified Antiviral Treatment Strategy for Hepatitis C in Myanmar

HIV Infections Clinical Trial

Official title:

Demonstration Project on Assessment of Simplified Antiviral Treatment Strategy for Hepatitis C in Myanmar

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03579576
• Other study ID #: EQUIPHCV01-MY
• Status: Completed
• Start date: December 20, 2017
• Est. completion date: June 30, 2019

Study information

• Verified date: June 2018
• Source: Right to Care
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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 including people who inject drugs (PWID) in Myanmar.

Description:

Affected populations will be screened for HCV and HIV and treated with direct a fixed-dose combination of sofosbuvir 400 mg/velpatasvir 100 mg (SOF/VEL) orally once daily 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 to 800 patients enrolled on treatment will be followed up at 4, 8, 12 and 24 weeks when Sustained Viral Load ( SVL) 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. In addition to assessing to assessing cost outcomes, the project will assess HCV treatment efficacy in terms of sustained virologic response at 12 weeks after end of HCV treatment (defined as undetected HCV RNA or less than lower limit of detection), compare the cost of low cost HCV viral assay platforms to standard of care, assess rates of ART initiation and virologic suppression of HIV-infected persons within the simplified HCV testing and treatment model and impact of HIV co-infection in participants on the HCV treatment outcome of sustained virologic response (SVR12). The project will be conducted 3 treatment sites in Yangon, Mandalay, and Kachin state in Myanmar.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 803
• Est. completion date: June 30, 2019
• Est. primary completion date: March 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Ability and willingness of participant to provide informed consent.

2. Men and women age 18 years.

3. 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. NOTE: If no medical records on HCV infection are available, active HCV infection must be confirmed by a detectable HCV RNA PCR prior to project entry.

4. Allowed HCV treatment history:

1. 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.

2. HCV treatment experienced with interferon with or without ribavirin only (no prior DAA treatment).

5. Chronic 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 HBsAg must be already on an active HBV regimen at study entry.

6. HIV-1 infection status must be documented as either absent or present, as defined below:

1. 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

2. Presence of HIV-1 infection, documented by rapid HIV test or HIV-1 ELISA test kit at any time prior to entry.

OR

3. HIV-1 infection confirmed by medical documentation as participant is registered in care at AIDS Center and receiving or preparing to initiate ARV treatment.

7. HIV co-infected participants taking ART or planning to initiate ART, should be:

1. Tolerating ART for at least 2 weeks without signs of needing to modify or discontinue the ART regimen before initiating HCV treatment.

AND

2. The ART regimen must be a regimen that can be co-administered with SOF/VEL.

8. Participants who are assigned to receive ribavirin as part of the treatment protocol must have hemoglobin =11.0 g/dL

9. For females of reproductive potential who will receive ribavirin, a negative urine pregnancy test (urine -HCG with a sensitivity of <25 mIU/mL) within 48 hours prior to project entry (HCV treatment initiation) must be documented.

10. 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.

11. Life expectancy >12 months, in the opinion of the site investigator

Exclusion Criteria:

1. 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).

2. Breastfeeding or pregnancy if patient will be receiving ribavirin.

3. Known allergy/sensitivity or any hypersensitivity to components of drug(s) or their formulation.

4. Acute tuberculosis (TB) infection. They will be followed and offered enrolment when they complete TB treatment.

5. 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/VEL is contraindicated (https://www.mdcalc.com/mdrd-gfr-equation).

6. Unwilling to provide informed consent for participation in the project.

7. Prior treatment with any HCV Direct Acting Agents (DAA).

8. Unable or unwilling to adhere to the HCV treatment course and monitoring in the opinion of the investigator.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis C
• HIV Infections

Intervention

Drug:
• sofosbuvir 400 mg/velpatasvir 100 mg (SOF/VEL) orally once daily for 12 weeks with or without weight-based ribavirin.
Direct Acting anti-HCV drugs given to all HCV infected participants at baseline.Those with Co-infections like HIV and or HBV will be given treatment as per national guidelines.

Locations

Country	Name	City	State
Myanmar	Waimaw	Kachen	Kachin
Myanmar	Myanmar Liver Foundation Clinic	Mandalay
Myanmar	Myanmar Liver Foundation Charity Clinic	Yangon

Sponsors (6)

Lead Sponsor	Collaborator
Right to Care	Boston University, Community Partners International, Ministry of Health and Sports, Myanmar, Myanmar Liver foundation (MLF), University of California, Los Angeles

Country where clinical trial is conducted

Myanmar, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 SVR12 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 study will also estimate the average cost to "produce" a successful outcome (SVR12), 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.
Primary	Overall Sustained Viral load response (SVR12) across all groups of HCV genotype, fibrosis stage, HIV and HBV co-infection.	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 Care cascade 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	HCV genotype and subtype	HCV Genotype and subtypes will be determined at entry for all patients. Frequency of resistance associated substitutions (RAS) among participants registered for the project will also be determined.	At baseline
Secondary	Validity and reliability of Cepheid GeneXpert in monitoring SVR12	150 patients will be evaluated for HCV viral load at entry and exit ( SVR12) comparing cepheid Gene Xpert and Roche real time PCR ( Standard method)	Testing done at baseline and 24 weeks
Secondary	HIV Viral load among HCV/HIV co-infected patients	HCV/HIV co-infected patients will either 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 HIV-infected persons within the simplified HCV testing and treatment model.	HIV Viral load at 24 weeks ( 12 weeks post HCV treatment)