study of quadruple therapy with eltrombopag for chronic hepatitis c

Conditions: Thrombocytopenia; Hepatitis C

Summary: this study will provide chronic hepatitis c patients with low platelets (less than 75x10\^9/l) the opportunity to undergo treatment and possible cure of their virus. the main hepatitis c drugs will be administered as standard of care, with the addition of the study drug eltrombopag. the investigators hypothesize that providing eltrombopag to chronic hepatitis c patients with low platelets (less than 75x10\^9/l) will permit the initiation and completion of antiviral triple therapy with boceprevir, ribavirin, and pegylated-interferon.

squelch-c is an investigator-initiated, single arm, non-blinded pilot study on the use of eltrombopag in combination with ribavirin, pegylated-interferon, and boceprevir, for patients who would not otherwise be treatment candidates because of low platelet counts (less than 75x10\^9/l). administration of the drugs ribavirin and boceprevir will be standard of care, with one exception for interferon. the total drug treatment period for the study patient will range from 32 - 56 weeks, depending on liver disease stage and viral response. follow-up will take place at 12 and 24 weeks post treatment to evaluate for sustained viral response. total study participation may require 1.5 years.

Eligibility criteria:
inclusion criteria: * male and female patients at least 18 years of age. * require a platelet count below 75 x 10\^9 /l at time of screening. * the patients must meet the eligibility criteria for all drugs involved. * only genotype 1 (a, b, indeterminate, or mixed). * confirmed history of chronic hepatitis c. * cirrhotic patients will be included. * liver imaging within 1 year to exclude hepatocellular carcinoma (hcc) is required in patients with cirrhosis. * patients without evidence of cirrhosis but meeting platelet criteria will also be admitted to study. * subjects must be able to provide informed consent, comply with drug administration instructions, and be able to complete each study visit. * ability to cover costs of ribavirin, interferon, and boceprevir will also be required. * female subjects are eligible if: non-pregnant, non-childbearing potential, or of childbearing potential and willing to perform complete abstinence or correctly use a form of birth control during intercourse \[barrier method, intrauterine device, hormonal therapy, or surgical sterilization in females or male partner\]. they must also be willing to have pregnancy tests performed every 4- weeks until 6 months after completion of ribavirin. * male study participants must agree to use a condom and their female partner must partake in one of the contraceptive methods discussed above until 6 months after completion of ribavirin therapy. exclusion criteria: * a history of chronic infection (i.e., hiv or hbv) or a previous organ transplantation. * a history of a platelet disorder. * a poorly controlled underlying medical illness (i.e., diabetes, hypertension, coronary artery disease, congestive heart failure, etc.). * any contraindication to any study drugs as mentioned in their respective prescribing information. * patients with decompensated cirrhosis defined as current evidence for ascites, encephalopathy, infection or variceal bleeding. all patients should be considered child-pugh class a. * patients with aminotransferase levels ≥ 500 iu/l will be excluded on presumption of another active liver disease. * patients must not be pregnant or nursing. * the study physician maintains the right to exclude a patient for a medical condition not listed above or based off laboratory values indicating chronic disease discovered at screening. * patients with eye disease may be excluded from this study if the ophthalmologist does not recommend treatment. * subjects with known hypersensitivity reactions (such as stevens-johnson syndrome, toxic, epidermal necrolysis, and erythema multiforme to ribavirin) to study drugs or any component of the products. * subjects with autoimmune hepatitis, hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), creatinine clearance less than 50 ml/min. * co-administration of drugs that are highly dependent on cyp3a4/5 for clearance and cyp3a4/5 inducers (see table 2 in boceprevir prescribing information).

Keywords: thrombocytopenia hepatitis platelets eltrombopag liver disease antiviral treatment