Clinical trial NCT03093415: Hepatitis C Treatment in PWIDs: MAT or Syringe Exchange Assisted-therapy vs Standard of Care
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C
Substance Use Disorders
Substance Abuse, Intravenous
Keywords: Hepatitis C
HCV
People Who Inject Drugs
PWID
Medication Assisted Therapy
MAT
Needle Exchange Program
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2017-03-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two parallel investigational groups in different community health clinic treatment settings assigned to treatment with elbasvir-grazoprevir as compared to an academic hepatology clinic retrospective cohort treated with elbasvir-grazoprevir.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: SVR 12
timeFrame: 24 weeks post-initiation of treatment (12 weeks post-completion of treatment)
Secondary outcomes:
measure: SVR 48
timeFrame: 60 weeks post-initiation of treatment (48 weeks post-completion of treatment)
measure: Discontinuation Rate or Lost To Follow Up
timeFrame: Study duration (60 weeks)
measure: NS5A Resistance
timeFrame: At Study Screening/Enrollment
measure: Medication Adherence
timeFrame: 12 weeks (duration of treatment)
measure: Injection Drug Use Relapse (IDU)
timeFrame: Duration of study (60 weeks)
Other outcomes:
Locations:
city: Portland
country: United States
facility: Old Town Clinic
state: Oregon
city: Portland
country: United States
facility: Outside In
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Atif Zaman, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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(Suppl 2):S56-61. doi: 10.1093/cid/cit271.
citation: 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 2:S80-9. doi: 10.1093/cid/cit306.
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. doi: 10.1016/j.jsat.2005.06.002.
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 multidisciplinary care and peer support. Eur J Gastroenterol Hepatol. 2010 Mar;22(3):270-7. doi: 10.1097/meg.0b013e32832a8c4c.
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 centre. Can J Gastroenterol. 2013 Apr;27(4):217-23. doi: 10.1155/2013/515636.
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. doi: 10.1016/j.drugpo.2015.04.012. Epub 2015 Apr 29.