Hepatitis C Treatment in PWIDs: MAT or Syringe Exchange Assisted-therapy vs Standard of Care

Hepatitis C Clinical Trial

Official title:

A Prospective Cohort Study Comparing the Effectiveness of Zepatier for the Treatment of Hepatitis C in an Academic Center Population to People Who Inject Drugs (PWIDs) in a Safety Net Clinic Setting Engaged in Either a Medication Assisted Therapy (MAT) or Syringe Exchange Program

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03093415
• Other study ID #: CRS00002743
• Status: Completed
• Phase: Phase 4
• Start date: May 30, 2017
• Est. completion date: June 6, 2019

Study information

• Verified date: October 2020
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

hepatitis C virus (HCV) has traditionally been treated in subspecialty health centers given the complexity of older pegylated interferon containing regimens, formerly the standard of care. This model has persisted into the modern era of direct anti-viral agents (DAAs) despite their relative simplicity, creating a bottleneck of human resources necessary to fight the largest infectious epidemic in North America. In addition, stigma and fear over cost has lead payers to restrict treatment in People Who Inject Drugs (PWIDs), even though a majority of new infections occur in this population. This study evaluates the effectiveness of treatment of HCV with elbasvir-grasoprevir in PWIDs in a real world, community health clinic setting. There are two prospective cohorts of PWIDs of 25 patients each, both in primary care-based community health clinics in Portland, Oregon. Cohort one is actively engaged with ambulatory medication assisted therapy with buprenorphine or extended released injectable naltrexone. Cohort two maintains active injection drug use with needle exchange and risk reduction education. These groups are compared to a 50 patient retrospective cohort of people with substance use disorders at tertiary care hepatology-based treatment program. All patients have genotype 1 or 4 HCV and are treated with elbasvir-grasoprevir for 12 weeks. The investigators hypothesize there is no difference in sustained viremic response at 12 or 48 weeks post-completion of treatment (SVR 12, 48) when treating patients in a community health clinic setting as compared to the standard-of-care subspecialty setting.

Description:

Hepatitis C has traditionally been treated in subspecialty health centers given the complexity of older pegylated interferon containing regimens, formerly the standard of care. This model has persisted into the modern era of direct anti-viral agents (DAAs) despite their relative simplicity, creating a bottleneck of human resources necessary to fight the largest infectious epidemic in North America. In addition, stigma and fear over cost has lead payers to restrict treatment in People Who Inject Drugs (PWIDs), even though a majority of new infections occur in this population. This study evaluates the effectiveness of treatment of hepatitis C virus (HCV) with elbasvir-grasoprevir in people who inject drugs (PWIDs) in a real world, community health clinic setting. There are two prospective cohorts of PWIDs of 25 patients each, both in primary care-based community health clinics in Portland, Oregon. Cohort one is actively engaged with ambulatory medication assisted therapy with buprenorphine or extended released injectable naltrexone. Cohort two maintains active injection drug use with needle exchange and risk reduction education. These groups are compared to a 50 patient retrospective cohort of people with substance use disorders at tertiary care hepatology-based Academic Health Center. All patients have genotype 1 or 4 HCV and are treated with elbasvir-grasoprevir for 12 weeks. The investigators exclude patients who: are under the age of 18; have a history of liver transplant; have failed past treatment of HCV; have an Aspartate aminotransferase Platelet Ratio Index (APRI) > 0.7 or APRI >0.7 but fibrosure/fibroscan of F2 or less; patients with genotype 1a and Nonstructural 5a (NS5a) resistance associated variants (RAVs); have clinical or radiologic evidence of cirrhosis; have aminotransferase levels >10x upper limit of normal; have a hemoglobin of less than 11g/dL, and are co-infected with hepatitis B or HIV. The investigators hypothesize there is no difference in sustained viremic response at 12 or 48 weeks post-completion treatment (SVR 12, 48) when treating patients with a DAA in a community health clinic setting as compared to the standard-of-care subspecialty setting.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: June 6, 2019
• Est. primary completion date: June 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Genotype 1b and genotype 1a without baseline NS5A resistance or Genotype 4
• APRI Score <0.7; if >0.7 a Fibrosure/Fibrotest or Fibroscan score of F2 or less
• No clinical or laboratory evidence of cirrhosis
• Readiness for treatment based on ability to make >2/3 sequential office visits
• Patients must be assessed to have decision-making capacity, be capable of consenting, and not be displaying evidence of overt intoxication.

Exclusion Criteria:

• Clinical or Laboratory Evidence of Cirrhosis
• Elevated prothrombin time unrelated to anticoagulation, hemoglobin level less than 12.3 g/L in females and <14 g/L in males, platelet count <150 × 109 cells/L), white blood cells (WBC) <4.0 x103/mm3 , aminotransferase levels more than 10 times the upper limit of normal, or albumin level <3.5 g/L.
• Previous treatment for hepatitis C infection
• Hepatocellular carcinoma
• HIV or hepatitis B virus co-infection
• Subjects taking medications that are contra-indicated to administer with Zepatier including phenytoin, carbamazepine, rifampin, St. John's Wort, and cyclosporine AND unable to change these medications to one without interactions.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Substance Abuse, Intravenous
• Substance Use Disorders
• Substance-Related Disorders

Intervention

Drug:
• elbasvir-grazoprevir (50 mg/100 mg)
12 week treatment of elbasvir-grazoprevir (50 mg/100 mg)

Locations

Country	Name	City	State
United States	Old Town Clinic	Portland	Oregon
United States	Outside In	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Oregon Health and Science University

Country where clinical trial is conducted

United States, 

References & Publications (7)

Aspinall EJ, Corson S, Doyle JS, Grebely J, Hutchinson SJ, Dore GJ, Goldberg DJ, Hellard ME. Treatment of hepatitis C virus infection among people who are actively injecting drugs: a systematic review and meta-analysis. Clin Infect Dis. 2013 Aug;57 Suppl — View Citation

Bruggmann P, Litwin AH. Models of care for the management of hepatitis C virus among people who inject drugs: one size does not fit all. Clin Infect Dis. 2013 Aug;57 Suppl 2:S56-61. doi: 10.1093/cid/cit271. Review. — View Citation

Grebely J, Knight E, Genoway KA, Viljoen M, Khara M, Elliott D, Gallagher L, Storms M, Raffa JD, DeVlaming S, Duncan F, Conway B. Optimizing assessment and treatment for hepatitis C virus infection in illicit drug users: a novel model incorporating multid — View Citation

Islam MM, Topp L, Conigrave KM, White A, Reid SE, Grummett S, Haber PS, Day CA. Linkage into specialist hepatitis C treatment services of injecting drug users attending a needle syringe program-based primary healthcare centre. J Subst Abuse Treat. 2012 Dec;43(4):440-5. doi: 10.1016/j.jsat.2012.07.007. Epub 2012 Aug 29. — View Citation

Mason K, Dodd Z, Sockalingam S, Altenberg J, Meaney C, Millson P, Powis J. Beyond viral response: A prospective evaluation of a community-based, multi-disciplinary, peer-driven model of HCV treatment and support. Int J Drug Policy. 2015 Oct;26(10):1007-13 — View Citation

Newman AI, Beckstead S, Beking D, Finch S, Knorr T, Lynch C, MacKenzie M, Mayer D, Melles B, Shore R. Treatment of chronic hepatitis C infection among current and former injection drug users within a multidisciplinary treatment model at a community health — View Citation

Sylvestre DL, Litwin AH, Clements BJ, Gourevitch MN. The impact of barriers to hepatitis C virus treatment in recovering heroin users maintained on methadone. J Subst Abuse Treat. 2005 Oct;29(3):159-65. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SVR 12	Sustained Viremic Response at 12 weeks post-completion of treatment. SVR12 was determined negative if undetectable (<20 copies) by polymerase chain reaction and positive if EITHER loss-to-follow up and no lab data or virus was detected greater than 20 copies.	24 weeks post-initiation of treatment (12 weeks post-completion of treatment)
Secondary	SVR 48	Sustained Viremic Response at 48 weeks post-completion of treatment (SVR48). Participants "Achieving SVR48" had a negative hepatitis C real time polymerase chain reaction (RT-PCR) test at 48 weeks after end of treatment. Participants who "Did Not Achieve SVR48" had a positive hepatitis C RT-PCR test at 48 weeks after end of treatment.	60 weeks post-initiation of treatment (48 weeks post-completion of treatment)
Secondary	Discontinuation Rate or Lost To Follow Up	Percentage of patients discontinuing medications prior to completion of 12 weeks or being lost to follow up, defined as inability to reach patient after 3 attempts and patients not following up with primary endpoint labs (SVR 12, 48)	Study duration (60 weeks)
Secondary	NS5A Resistance	Percentage of patients with genotype 1a and NS5A Resistance-Associated Variants (RAVs)	At Study Screening/Enrollment
Secondary	Medication Adherence	Adherence determined by client/subject self-reported medication adherence measured by percentage of pills taken on a monthly basis. Categorically separated into < 90% adherence, 90-99% adherence, 100% adherence.	12 weeks (duration of treatment)
Secondary	Injection Drug Use Relapse (IDU)	Self reported relapse IDU following HCV treatment (MAT arm)	Duration of study (60 weeks)